Cognitive impairment is a common issue for people with multiple sclerosis (MS), affecting their daily lives and work. This study aimed to report the cognition and employment status of participants with highly active relapsing MS (RMS) treated with cladribine tablets (CladT) during the 2-year, open-label, single-arm, Phase 4 CLARIFY-MS study. In this post hoc analyses, 482 participants with highly active RMS received at least one dose of CladT. Cognitive function was assessed using the Brief International Cognitive Assessment for MS (BICAMS) at the start of the study (baseline [BL]), and at 12 and 24 months (M) after initiating treatment with CladT (n = 399). Symbol Digit Modalities Test (SDMT) scores were further analysed to check for clinically meaningful changes (4- and 8-point) from BL to M24. Employment status was also evaluated. Cognitive function: BICAMS parameter scores remained stable over 24 months. Most participants showed stable or improved cognitive processing speed, as measured by clinically meaningful 4- and 8-point changes in the SDMT scores  from BL to M24. Employment status: No major differences in the employment status of participants were observed over 2 years, with > 40% of participants being in full-time employment during the study. Most CLARIFY-MS participants with highly active RMS treated with CladT showed clinically meaningful improvements and stability in SDMT scores at M24 compared to BL, with overall cognitive function (BICAMS scores) remaining stable over 2 years. Despite the challenges posed by the COVID-19 pandemic, most participants maintained stable employment over 24 months, supporting the positive quality-of-life outcomes associated with CladT and supporting its overall efficacy in treating RMS.
Multiple sclerosis (MS) is a chronic immune-mediated inflammatory disease of the central nervous system, often accompanied by fatigue and reduced quality of life (QoL). Stressful life events (SLEs) may heighten stress in people with MS (pwMS), compounding the challenges of living with the condition. While mastery is acknowledged as a psychological resource for resilience, its protective role against SLEs remains unclear. We examined whether mastery modifies associations between SLEs and QoL and fatigue in pwMS. We analysed cross-sectional survey data from an international sample of 948 pwMS. Mastery (Pearlin mastery scale) was categorised into tertiles (low, moderate, high). QoL (MSQoL-54) was summarised as mental and physical composite scores. Clinically significant fatigue was defined as fatigue severity scale (FSS) > 5. SLEs exposure (Holmes-Rahe social readjustment rating scale) was assessed as total number and load (severity). Multivariable regression models assessed associations between SLEs and outcomes, and interaction terms tested effect modification by mastery. Higher number and load of SLEs were associated with clinically meaningful lower mental QoL (- 7 to - 8 points) among pwMS with low or moderate mastery, but not among pwMS with high mastery. Higher number and load of SLEs were also associated with 3- 5 fold higher odds of clinically significant fatigue, primarily among pwMS with low mastery. Higher mastery may buffer adverse associations between SLEs exposure and mental QoL and fatigue. Prospective studies are needed to confirm temporal relationships; however, interventions that support mastery may help mitigate stress-related impacts on wellbeing in MS.
With aging population, an increasing proportion of spontaneous intracerebral hemorrhage (ICH) occur in patients receiving anticoagulation for atrial fibrillation (AF). Left atrial appendage (LAA) closure has emerged as an alternative strategy. In the absence of population-level data, this study aimed to estimate the incidence of ICH among patients with AF who could potentially be eligible for LAA closure and to extrapolate these findings to the national level. All cases of ICH were prospectively identified from the population-based Dijon Stroke Registry, France (2013-2022). Eligibility for LAA closure was assessed among patients with AF after excluding those who died within 30 days, had another indication for long-term anticoagulation, or a CHA₂DS₂-VA score <2. Annual incidence rates were calculated by age groups and sex. Nationwide estimates were derived by standardizing age- and sex-specific incidence to the French population. Among 369 ICH cases, 104 (28.2%) occurred in patients with AF, of whom 36 were considered eligible for LAA closure (mean age: 80.7 ±11.2 years; 52.8% women). Crude incidence of eligible ICH was 2.3 per 100,000 person-years (95% CI, 1.6-3.2). After standardization, the estimated number of eligible patients in France was 1,732 in 2022, projected to reach 2,354 by 2035 and 2,780 by 2050. Approximately one in four ICH cases occurs in patients with AF, but only a small proportion would be theoretically eligible for LAA closure. These population-based estimates provide essential data to inform healthcare planning and guide future clinical trials evaluating LAA closure in this high-risk population.
Neurobrucellosis is a rare but serious complication of systemic Brucella infection, occurring in approximately 3-15% of cases and accounting for about 0.5% of all community-acquired central nervous system (CNS) infections. Although uncommon, it poses significant diagnostic challenges and carries the risk of long-term neurological sequelae. This review provides a comprehensive overview of the epidemiology, pathogenesis, clinical manifestations, diagnostic strategies, and management of neurobrucellosis, with an emphasis on current evidence and diagnostic difficulties. A thorough literature review was conducted, incorporating clinical studies, case series, and reviews addressing various aspects of neurobrucellosis. Neurobrucellosis can affect both the central and peripheral nervous systems. Central involvement includes meningitis, meningoencephalitis, cranial neuropathies-most commonly affecting the eighth cranial nerve-white matter lesions, vascular complications, and spinal cord syndromes such as arachnoiditis or transverse myelitis. Peripheral nervous system involvement, though less frequent, may present as polyradiculoneuropathies or mimic Guillain-Barré syndrome. Diagnosis is based on clinical suspicion supported by cerebrospinal fluid analysis, serologic testing, neuroimaging, and molecular methods such as PCR. MRI is the imaging modality of choice, although up to 60% of cases may show no abnormalities. Treatment typically consists of a prolonged combination antibiotic regimen tailored to disease severity and localization. Neurobrucellosis requires early recognition and prompt, appropriate antibiotic therapy to reduce the risk of permanent neurological damage. A high index of suspicion is essential, particularly in endemic regions or in patients with unexplained neurological symptoms and epidemiologic risk factors.
In Ausimmune, an Australian multicenter incident case-control study, Epstein-Barr virus (EBV)-related measures, including anti-EBNA antibodies and infectious mononucleosis, show multiple sclerosis (MS) associations mediated by DNA methylation (DNAm). Human herpesvirus-6 (HHV-6) DNA has also been linked to increased MS onset risk, though its mechanisms remain unknown. Therefore, we examined an expanded set of human herpesvirus indices including HHV-6 indices. We first tested associations with MS-associated DNAm modules, then assessed whether HHV-6 DNA contributes to MS onset through DNAm pathways. Serological (serum) and viral load (whole blood) measures of EBV (DNA, viral capsid antigen, early antigen diffuse and restricted), HHV-6 (DNA, IgM, IgG), cytomegalovirus (CMV) (IgG), and varicella zoster virus (DNA, IgG) were collected. DNAm was measured from whole blood (Illumina Infinium Human Methylation EPIC v1). DNAm-module (A1-A5) scores were derived using an epigenome-wide association study for MS onset risk and dimension-reduction methods. A total of 206 cases and 348 matched controls were analyzed. Multivariable linear regression demonstrated associations between HHV-6 DNA positivity and the A2-module, and between higher CMV IgG and the A4 module. Counterfactual mediation analysis indicated that 45% of the positive association of HHV-6 DNA positivity with MS onset risk was mediated through the A2 module (P indirect = .008). The A2 module showed enrichment for lymphatic and immune pathways. These results provide evidence for a distinct DNAm module as a plausible mechanism underlying the associations of HHV-6 with MS onset. Importantly, these epigenetic pathways appear to mediate associations with human herpesviruses beyond EBV. These findings provide further insights into how environmental factors relate to MS onset through epigenetic programming.
Longitudinally extensive transverse myelitis (LETM) is a severe inflammatory spinal cord disorder. It is commonly associated with neuromyelitis optica spectrum disorders and other autoimmune conditions like Sjögren syndrome, infectious and idiopathic aetiologies. Interleukin-6 (IL-6) is one of the key pro-inflammatory cytokines implicated in neuroinflammation and may serve as an important biomarker of disease activity. To evaluate the correlation between cerebrospinal fluid (CSF) IL-6 levels and disease activity in patients with LETM and to assess its prognostic value for short-term functional outcomes. In this prospective follow-up study conducted over 18 months, 41 patients with LETM and 21 controls with non-inflammatory neurological conditions were enrolled. Disease severity was assessed using the Expanded Disability Status Scale (EDSS) at admission and at 3-month follow-up. CSF IL-6 levels were analysed and correlated with clinical and radiological variables using Spearman correlation, receiver operating characteristic (ROC) analysis and multivariate regression. Median CSF IL-6 levels were significantly higher in LETM patients than controls (11.26 vs 5.02 pg/mL; p<0.001). CSF IL-6 showed a moderate positive correlation with EDSS at admission (ρ=0.34, p=0.027) and follow-up (ρ=0.51, p<0.001). ROC analysis demonstrated fair predictive accuracy for severe disease (AUC=0.70), with a cut-off of approximately 7 pg/mL. Multivariate analysis identified CSF IL-6 as an independent predictor of disease severity. CSF IL-6 correlates with disease activity and disability in LETM and may serve as a useful biomarker for prognostication and treatment planning.
A prior non-randomized study suggests that potassium supplementation may improve survival among furosemide initiators, and a randomized trial suggests that salt substitutes containing potassium might lower stroke risk. We conducted a retrospective cohort study using health-care data to confirm or refute these associations among new users of furosemide. The exposure of interest was empiric potassium dispensing (yes/no) concurrent with furosemide initiation. Outcomes were all-cause mortality, sudden cardiac arrest/ventricular arrhythmia (SCA/VA), and stroke. Primary as-started and secondary as-treated analyses were performed with Cox proportional hazards regression. We used inverse probability of treatment weighting (IPTW) to control for confounding, with weights calculated from high-dimensional propensity scores. We identified 511 462 and 320 703 initiators of furosemide <40 and ≥40 mg/day with 21.5% and 35.3%, respectively, starting empiric potassium supplementation. In initiators of furosemide <40 mg/day with (vs. without) empiric potassium, as-started IPTW-hazard ratios (HRs) were 1.02 (95%CI 1.01-1.04) for death, 1.00 (0.94-1.04) for SCA/VA, and 1.03 (1.00-1.06) for stroke. Similarly, in initiators of furosemide ≥40 mg/day with (vs. without) empiric potassium, as-started IPTW-HRs were 1.02 (1.00-1.03) for death, 0.98 (0.94-1.03) for SCA/VA, and 1.01 (0.98-1.04) for stroke. We did not observe associations suggesting a clinically meaningful effect of empiric potassium supplementation among furosemide users. However, given the high prevalence of furosemide use among highly heterogeneous patient populations, a large pragmatic trial may be warranted to more definitively evaluate the potential benefits and harms of empiric potassium supplementation among furosemide initiators.
Systemic vasculitis is a multisystem inflammatory disorder that may exacerbate cerebrovascular injury and complicate the clinical course of acute ischemic stroke (AIS). This study aimed to assess the associations between systemic vasculitis and hospitalization outcomes in adults admitted for AIS. Adults hospitalized with a principal diagnosis of acute ischemic stroke were identified from the US Nationwide Inpatient Sample (2006-2020). After exclusions, patients with systemic vasculitis were matched 1:4 to those without vasculitis using propensity score matching. Survey-weighted logistic and linear regression models were used to evaluate in-hospital outcomes, complications, length of stay, and total hospital charges, with stratified analyses by chronic kidney disease, heart failure, and systemic autoimmune disease status. Among 1,283,209 eligible AIS hospitalizations, 2,594 patients with systemic vasculitis were matched to 10,376 patients without vasculitis. After adjustment, systemic vasculitis was associated with higher risks of in-hospital mortality (aOR = 1.24, 95% CI: 1.01-1.51), any complication (aOR = 1.13, 95% CI: 1.03-1.24), venous thomboembolism (aOR = 1.66, 95% CI: 1.29-2.14), sepsis/shock (aOR = 1.54, 95% CI: 1.30-1.83), acute kidney injury (aOR = 1.15, 95% CI: 1.01-1.30), and delirium or altered mental status (aOR = 2.26, 95% CI: 1.53-3.32). Systemic vasculitis was also associated with longer LOS (adjusted β = 1.38 days, 95% CI: 1.15-1.60) and higher total hospital charges (adjusted β = 19.91 thousand USD, 95% CI: 14.73-25.09). Stratified analyses showed generally consistent associations for LOS and hospital charges, although individual complications varied across subgroups. Systemic vasculitis is independently associated with worse in-hospital outcomes among adults hospitalized for AIS, including higher mortality, greater risks of major complications, longer hospitalization, and higher hospital charges. These findings highlight the need for careful inpatient monitoring and individualized management in this high-risk population.
Recent studies have reported conflicting results regarding the mortality risk in patients with myasthenia gravis (MG); however, evidence from East Asian populations remains limited. Understanding the mortality patterns and risk factors of MG is essential for improving patient outcomes. We conducted a nationwide, retrospective cohort study using data from the Korean National Health Insurance Service database to investigate mortality and its associated factors in patients with MG. Incident MG cases diagnosed between 2005 and 2020 were identified based on validated operational definitions and matched 1:5 with age- and sex-matched controls. All-cause mortality was assessed using Kaplan-Meier analysis, and mortality-associated risk factors were identified by multivariate Cox regression after adjusting for variables. This study included 21,642 patients with MG and 108,210 matched controls. The MG group showed a significantly higher mortality rate than that in controls (144.40 vs. 92.60 per 10,000 person-years; adjusted hazard ratio 1.41, 95% CI 1.34-1.49). Risk factors associated with increased mortality included older age, male sex, high comorbidity burden, high-dose corticosteroid use (≥15 mg/day), thymoma, and myasthenic crisis. Thymectomies were associated with reduced mortality. The leading causes of death included malignancy, cardiac disease, and MG. Myasthenic crisis and thymoma were respectively associated with early mortality and a gradual increase in late mortality. This study demonstrated increased mortality in Korean patients with MG, identifying key disease- and treatment-related risk factors. These findings underscore the need for early risk stratification, comorbidity management, and individualized treatment approaches to improve long-term outcomes.
Introduction Alzheimer's disease and other dementias (ADOD) represent an escalating challenge for global health systems. This study evaluates spatiotemporal trends in ADOD burden from 1990 to 2023 and forecasts incidence trajectories in China through 2035. Methods Using the Global Burden of Disease Study 2023, we analyzed ADOD metrics globally, by Socio-demographic Index (SDI) quintile, and across China. Temporal trends were assessed via estimated annual percentage changes (EAPCs) and compound annual growth rates (CAGRs). Absolute burden shifts were partitioned into population growth, population aging, and epidemiological change using the Dash-Gupta decomposition. Future China-specific incidence was projected using a Bayesian age-period-cohort (BAPC) model. Results Global age-standardized incidence rates (ASIR) exhibited a marginal increase (EAPC 0.06), with progressively higher rates across increasing SDI levels. Decomposition analysis identified population growth as the dominant contributor to rising incidence, peaking in low SDI regions (94.72%), whereas population aging contributed more substantially in high SDI (21.34%). China recorded the fastest ASIR growth (EAPC 0.42), with estimated contributions from both population aging (20.03%) and the epidemiological change (15.71%), particularly within the 60-79 age cohorts. While global mortality and disability-adjusted life-years shifted toward the oldest-old (≥ 80 years), China experienced a disproportionate incidence increase among the younger-old (70-74 years; CAGR 1.10% vs global 0.27%). However, BAPC projections suggest a plateau or decline in incidence among the younger-old in China, contrasted by persistent increases among the oldest-old, with the most pronounced growth observed in the ≥ 95-year cohort. Conclusion China is undergoing a distinct dementia transition characterized by rising younger-old incidence and prolonged disease duration. This pattern suggests a need to combine earlier risk reduction with strengthened integrated long-term care for the oldest-old. The trajectory serves as a reference for rapidly aging middle-to-high SDI nations.
Seizure control is the primary therapeutic goal in pediatric epilepsy, yet its multidimensional impact on health-related quality of life (HRQoL) and family functioning remains insufficiently defined. This study examined the association between seizure control status and HRQoL in Chinese children with epilepsy, and explored correlates of seizure control. In this prospective questionnaire-based study, 191 children with epilepsy aged 4-18 years were enrolled after staged screening and classified into seizure-controlled (≥6 months seizure freedom; n = 146) and seizure-uncontrolled groups (n = 45). HRQoL was assessed using the Chinese version of the Quality of Life in Childhood Epilepsy Questionnaire-16 (QOLCE-16). Demographic, clinical, and family-related variables were collected. Group comparisons were conducted using appropriate statistical tests. Exploratory machine learning models were applied to identify factors associated with seizure control status. Children in the seizure-controlled group had significantly higher QOLCE total raw scores, standardized scores, and social functioning scores than those in the seizure-uncontrolled group (all P < 0.05). No significant differences were observed in cognitive, emotional, or physical functioning domains. Family caregiving patterns and economic burden were largely comparable between groups. Machine learning models demonstrated modest performance; feature importance analyses identified age, emotional HRQoL, overall QOLCE scores, and caregiver education level as variables associated with seizure control. Sustained seizure control is associated with better overall HRQoL in children with epilepsy, particularly in social functioning, while other domains and family burden may persist beyond seizure status alone. These findings support integrated management strategies that address both seizure control and psychosocial well-being.
As a neurodegenerative disease, motor neuron disease (MND) is associated with a poor prognosis and imposes substantial economic and social burdens. Currently, hospital admissions for MND show rapid growth in China, yet assessments of the national disease burden of China remain insufficient. Therefore, we aims to systematically evaluate the disease burden of MND in China. Using the data from Global Burden of Diseases 2023 (GBD 2023), we analyzed the incidence, prevalence, mortality, years of life lost (YLL), years lived with disability (YLD), and disability-adjusted life-years (DALY) of MND in China from 1990 to 2023. Decomposition analysis was used to quantify factors influenced disease burden. And locally weighted regression was used to estimate the relationship between socio-demographic index (SDI) and age-standardized rate due to MND. In 2023, China reported 8,085 incidence cases [95% uncertainty interval (UI): 6,546-9,782], 35,838 (95% UI: 28,946 to 43,309) prevalent cases and 2659 (95% UI: 1674 to 4876) deaths due to MND. Crude rates of prevalence, mortality and YLD in 2023 significantly exceeded 1990 levels. During 1990 to 2023, the age-standardised prevalence (ASPR) and age-standardised YLD rate of MND in China increased by 13.91% and 13.90%, respectively. In contrast, the age-standardised incidence rate (ASIR), the age-standardised mortality rate (ASMR) age-standardised YLL rate and age-standardised DALY rate (ASDR) for MND had significantly decreased. The burden of MND increased progressively with age in both sexes, with males exhibiting a higher burden than females in 2023. In China, the total MND-related deaths increased by 66.10% from 1990 to 2023, driven by rises in age-specific motality rates (3.13%), population growth (21.33%), and population aging (41.64%). And a negative association was observed between SDI and the age-standardized rates of incidence, prevalence, mortality, YLL, YLD, and DALY due to MND in China. The increase in ASPR and age-standardised YLD rate, despite the decline in ASIR, ASMR and ASDR and age-standardised YLL rate, which might confirms the extended survival rate of MND patients in China, which can be attributed to demographic transitions, advancements in diagnostic techniques, and improved therapeutic interventions. It is very important to study the accurate epidemiological data on MND for clinical diagnosis and treatment and health policy.
Persons with Parkinson's disease (pwPD) frequently experience psychosocial symptoms that are inadequately addressed by traditional clinical approaches. To evaluate the impact of Parkinson's Pals, a student-led virtual, intergenerational program, on psychosocial symptoms in pwPD and student knowledge. PwPD were paired with undergraduates for eight virtual meetings over  four months. Scores on the UCLA Loneliness Scale (UCLA-LS), Kissane Demoralization Scale (DS), Scales for Outcomes in Parkinson's Disease-Psychosocial Functioning (SCOPA-PS), Parkinson Disease Questionnaire-39 (PDQ-39), and student knowledge self-assessments were compared before and after program participation. Twenty-five pwPD-student pairs participated. There was significant improvement in median total UCLA-LS (p = 0.031) and DS (p < 0.001) scores but not SCOPA-PS or PDQ-39 scores (p > 0.05). Students also reported improved familiarity with PD (p < 0.001). Participation in Parkinson's Pals was feasible, reduced loneliness and demoralization in pwPD, and enhanced student education. Further studies are needed to explore the psychosocial benefits of intergenerational programs for pwPD.
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Social determinants of health (SDoH) are increasingly recognized as important contributors to neurological disorders, yet their joint association with migraine remains insufficiently explored. We analyzed 11,009 adults aged ≥20 years from the National Health and Nutrition Examination Survey (NHANES) 1999-2004. Self-reported severe headache or migraine was defined based on questionnaire item MPQ090. Multiple social determinants of health (SDoH) indicators were evaluated individually using weighted logistic regression and jointly using weighted quantile sum (WQS) regression in relation to self-reported severe headache or migraine. Several individual social determinants of health (SDoH) indicators were significantly associated with Self-Reported Severe Headache or Migraine. Overall, a higher SDoH burden was associated with increased odds of migraine (OR = 2.26, 95% CI 1.78-2.87, p <0.001), representing the comparison between the highest and lowest quartiles of the WQS index. In the WQS regression, housing status, education level, and family income-to-poverty ratio contributed most to the overall mixture effect. The accumulation of adverse SDoH was positively associated with self-reported severe headache or migraine. Housing conditions, educational attainment, and economic resources contributed most to the observed mixture effect, suggesting that social context may play an important role in migraine burden and prevention.
Stroke is the second leading cause of death and major cause of disability worldwide. Substantial regional variations exist in modifiable risk factor profiles, indicating the need for region-specific prevention strategies. Using the Global Burden of Disease (GBD) 2023 data, the burden, risk factor contributions, and future projections of stroke were compared across East Asia, Western Europe, and North America from 1990 to 2023, with forecasts to 2050. Deaths, disability-adjusted life years (DALYs), incidence, and prevalence of total stroke and the three subtypes were analyzed across 204 countries using GBD 2023 estimates. Temporal trends were assessed using estimated annual percentage changes. Changes in mortality were decomposed into population growth, population aging, and epidemiological components. Risk factor attribution was conducted within the GBD comparative risk assessment framework. The future burden through 2050 was projected using Bayesian age-period-cohort models with integrated nested Laplace approximation, incorporating intervention scenarios targeting systolic blood pressure (SBP), low-density lipoprotein (LDL) cholesterol, and ambient particulate matter (PM2.5). From 1990 to 2023, the global age-standardized stroke mortality rate declined by 51.7%, whereas the absolute deaths increased from 4.58 million to 6.55 million. A seven-fold disparity was observed across the socio-demographic index strata. High SBP was the leading risk factor globally, while the second-ranking factor differed: ambient PM2.5 in East Asia and high LDL cholesterol in Western Europe and North America. Population aging accounted for a 113.1% increase in stroke deaths in East Asia, whereas adverse epidemiological trends have contributed to increased mortality in North America. A 50% reduction in high SBP prevalence is projected to avert substantial stroke deaths annually by 2050. Population aging is expected to continue to increase the absolute stroke burden despite declining age-standardized rates. Regional heterogeneity in the risk factor profiles supports differentiated prevention strategies that combine hypertension control with targeted environmental or metabolic interventions.
Understanding secular trends in demographic patterns of multiple sclerosis (MS) may help elucidate its etiopathogenesis and is also important for future resource allocation and planning healthcare strategies. Though several incidence and prevalence studies exist, nationwide studies utilizing contemporary data collected over decades remain rare. The objective of this study was to determine changes in incidence and prevalence of MS in Sweden from 2001 to 2021. Leveraging data from multiple linked population-based registries, we utilized two case definitions, one administrative (based on International Classification of Disease codes from inpatient and outpatient visits, 2006-2021) and one clinical (based on the Swedish MS registry, 2001-2021). We estimated the overall and annual incidence and point prevalence using both definitions and age-standardized to the World Standard Population. Temporal trends in incidence and prevalence were analyzed using joinpoint and binomial regression, respectively. In total 13,055 incident and 28,107 prevalent MS cases were identified in the administrative data. The overall age-standardized incidence rate was 8.37 (95% confidence interval [CI] 8.22 - 8.51) cases per 100,000 person-years. Incidence rates were stable until 2012, then decreased until 2021 (annual percent change -2.51%; 95% CI -5.04% to -1.69%), which translated into a decrease in number of new MS cases from 796 in 2006 to 701 in 2021, or -12.0%. In the clinical data, the overall age-standardized incidence was 7.87 (95% CI 7.74 to 7.99) cases per 100,000 person-years. Incidence increased between 2001 and 2014 with an annual percent change of 2.00% (95% CI 1.40% to 2.84%) and thereafter decreased through to 2021 with an annual percent change of -2.84% (95% CI -5.06 to -1.49%). The age-standardized prevalence of MS in the administrative cohort increased from 118 cases per 100,000 (95% CI 116 to 120) in 2006 to 167 cases per 100,000 (95% CI 164 to 169) in 2021, i.e., an increase of 41.7%. Similarly, in the clinical cohort, prevalence increased from 71 (95% CI 69 to 72) to 154 (95% CI 151 to 156) cases per 100,000 persons from 2001 to 2021, representing an increase of 117.9% Conclusion: Our findings demonstrate a decreasing incidence of MS in the last decade, while prevalence continuously increased. Although confounding by changes in data density cannot be excluded, this may reflect changes in environmental exposures such as smoking, as well as contemporary treatment practices and a secular trend toward milder disease with reduced mortality.
Primary exercise headache (PEH) is a rare primary headache disorder that occurs specifically during or right after physical exertion and lasts up to 48 h. This study aimed to evaluate the epidemiology of PEH in clinic- and population-based settings. Pubmed/Medline, Embase, ScienceDirect, Scopus, and CINAHL Ultimate were thoroughly searched for articles that presented original data on the epidemiology of PEH and were published up to 16 July 2025. Random-effects meta-analysis was performed in order to calculate the pooled prevalence estimates (PPEs), where I2 statistics and prediction intervals (PIs) were used to measure the between-study heterogeneity. The study's structure adhered closely to the Meta-analyses of Observational Studies in Epidemiology (MOOSE) and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) requirements. The risk of bias in the included research was assessed using the Joanna Briggs Institute Checklist for Studies Reporting Prevalence Data. The protocol of the study was pre-registered on PROSPERO (CRD42024612283). Out of the original 2,083 records, 12 articles satisfied all inclusion requirements. The majority of the studies showed a low risk of bias. The headache is a rare finding in clinical-based settings (PPE = 0.46%, 95% confidence interval [CI]: 0.18-1.20, 95% PI: 0.01%-14.29%, I2 = 94.86), more common in population-based surveys (PPE = 4.92%, 95% CI: 1.84-12.49, I2 = 98.73), shows a female predominance, and, moreover, typically has onset in the late 20s (27.47 years). Our study showed that PEH is a rare primary headache disorder among adults evaluated for a headache in a clinic-based setting and is significantly more common in the general population. Furthermore, PEH is diagnosed within similar frequency among both sexes in headache-oriented clinics and moreover, predominantly in the late 20s. However, in the general population, there is a notable female preponderance.
Frailty is dynamic in later life, yet prospective evidence linking frailty trajectories to incident stroke across diverse populations is limited. To investigate the association between frailty trajectories and incident stroke risk in adults aged 50 years and older using data from three nationally representative cohorts. We analyzed harmonized data from three longitudinal cohorts: the English Longitudinal Study of Ageing (ELSA), the Health and Retirement Study (HRS), and the China Health and Retirement Longitudinal Study (CHARLS). Frailty was assessed using a deficit-accumulation frailty index at each wave. Frailty trajectories were identified using latent class mixed models, which classified participants into three groups: Low, Moderate, and Increasing-to-high. Incident stroke was ascertained through self-reported physician diagnosis. Associations between frailty trajectory group membership and incident stroke were assessed using Cox proportional hazards models in the pooled dataset, stratified by cohort, and adjusted for demographic, socioeconomic, lifestyle, and laboratory covariates. Among 19,666 participants, the median follow-up was 7.5 years (IQR 7.0-8.0), and 1,131 (5.8%) incident strokes occurred. In the fully adjusted model, compared with the Low trajectory group, the Moderate trajectory group had a significantly higher risk of incident stroke (HR 2.05, 95% CI 1.73-2.43), as did the Increasing-to-high group (HR 3.51, 95% CI 2.99-4.12) (both P < 0.001). Cohort-specific analyses showed consistent directions of association. Frailty trajectories were strongly associated with incident stroke risk across three prospective cohorts. Longitudinal frailty monitoring may help identify individuals at elevated stroke risk and inform targeted prevention strategies.
We aimed to evaluate the global burden, spatial disparities, and risk factors of early-onset ischemic stroke (EOIS). Using data from the Global Burden of Disease Study 2021, we estimated incidence, mortality, and DALYs. Health inequality was measured with Slope Index of Inequality (SII) and Concentration Index (CII). Frontier analysis assessed national efficiency. Age-period-cohort and decomposition models analyzed trends and drivers. Between 1990 and 2021, global age-standardized incidence, mortality, and DALYs for EOIS declined, but absolute cases rose due to population growth and aging. Males and populations in Central Asia and Eastern Europe had the highest burden. East Asia saw rising age-standardized incidence. Health inequalities widened globally, with countries like Nauru and Kiribati showing the largest gaps. High-SDI countries such as Lithuania and the U.S. demonstrated unmet healthcare efficiency. Incidence and mortality increased with age, especially in men over 35. Population aging and growth were key drivers. Leading risk factors included high LDL and hypertension, while high BMI, high ambient temperature, and sugar-sweetened beverages emerged as growing risks. Low whole grain intake was a major dietary risk. The absolute burden of EOIS has increased due to demographic shifts. Significant socio-demographic and regional disparities persist, with men and certain regions facing disproportionately high risks. Metabolic risks remain central, while emerging factors are gaining importance.