Neuroepidemiology

BACKGROUND: Determining the prevalence of neuromuscular disorders for the general population is important to identify the scope of burden on society and enable comparisons with other health conditions. This systematic review aims to identify and collate the findings of studies published between 1960 and 2013 on the prevalence of all types of muscular dystrophies. SUMMARY: Relevant articles were identified through electronic database searches and manual searches of reference lists. There were 38 articles from across 19 countries that met the inclusion criteria. The total combined prevalence for all muscular dystrophies for studies classified as having a low risk of bias ranged between 19.8 and 25.1 per 100,000 person-years. Myotonic dystrophy (0.5-18.1 per 100,000), Duchenne muscular dystrophy (1.7-4.2) and facioscapulohumeral muscular dystrophy (3.2-4.6 per 100,000) were found to be the most common types of disorder. There was wide variation in study methodology, case ascertainment, and verification procedures and populations studied, all of which may contribute to the wide prevalence range, in addition to the likely variation in prevalence by country. Key Messages: Greater consistency in the conduct and reporting of neuroepidemiological studies is urgently needed to enable comparisons to be made between studies, countries, and over time.

AIM: To estimate the prevalence of Alzheimer's disease (AD) and other dementias in the USA using a nationally representative sample. METHODS: The Aging, Demographics, and Memory Study sample was composed of 856 individuals aged 71 years and older from the nationally representative Health and Retirement Study (HRS) who were evaluated for dementia using a comprehensive in-home assessment. An expert consensus panel used this information to assign a diagnosis of normal cognition, cognitive impairment but not demented, or dementia (and dementia subtype). Using sampling weights derived from the HRS, we estimated the national prevalence of dementia, AD and vascular dementia by age and gender. RESULTS: The prevalence of dementia among individuals aged 71 and older was 13.9%, comprising about 3.4 million individuals in the USA in 2002. The corresponding values for AD were 9.7% and 2.4 million individuals. Dementia prevalence increased with age, from 5.0% of those aged 71-79 years to 37.4% of those aged 90 and older. CONCLUSIONS: Dementia prevalence estimates from this first nationally representative population-based study of dementia in the USA to include subjects from all regions of the country can provide essential information for effective planning for the impending healthcare needs of the large and increasing number of individuals at risk for dementia as our population ages.

Epilepsy is a chronic disease of the brain characterized by an enduring (i.e., persisting) predisposition to generate seizures, unprovoked by any immediate central nervous system insult, and by the neurobiologic, cognitive, psychological, and social consequences of seizure recurrences. Epilepsy affects both sexes and all ages with worldwide distribution. The prevalence and the incidence of epilepsy are slightly higher in men compared to women and tend to peak in the elderly, reflecting the higher frequency of stroke, neurodegenerative diseases, and tumors in this age-group. Focal seizures are more common than generalized seizures both in children and in adults. The etiology of epilepsy varies according to the sociodemographic characteristics of the affected populations and the extent of the diagnostic workup, but a documented cause is still lacking in about 50% of cases from high-income countries (HIC). The overall prognosis of epilepsy is favorable in the majority of patients when measured by seizure freedom. Reports from low/middle-income countries (LMIC; where patients with epilepsy are largely untreated) give prevalence and remission rates that overlap those of HICs. As the incidence of epilepsy appears higher in most LMICs, the overlapping prevalence can be explained by misdiagnosis, acute symptomatic seizures and premature mortality. Studies have consistently shown that about one-half of cases tend to achieve prolonged seizure remission. However, more recent reports on the long-term prognosis of epilepsy have identified differing prognostic patterns, including early and late remission, a relapsing-remitting course, and even a worsening course (characterized by remission followed by relapse and unremitting seizures). Epilepsy per se carries a low mortality risk, but significant differences in mortality rates are expected when comparing incidence and prevalence studies, children and adults, and persons with idiopathic and symptomatic seizures. Sudden unexplained death is most frequent in people with generalized tonic-clonic seizures, nocturnal seizures, and drug refractory epilepsy.

BACKGROUND: Global stroke epidemiology is changing rapidly. Although age-standardized rates of stroke mortality have decreased worldwide in the past 2 decades, the absolute numbers of people who have a stroke every year, and live with the consequences of stroke or die from their stroke, are increasing. Regular updates on the current level of stroke burden are important for advancing our knowledge on stroke epidemiology and facilitate organization and planning of evidence-based stroke care. OBJECTIVES: This study aims to estimate incidence, prevalence, mortality, disability-adjusted life years (DALYs) and years lived with disability (YLDs) and their trends for ischemic stroke (IS) and hemorrhagic stroke (HS) for 188 countries from 1990 to 2013. METHODOLOGY: Stroke incidence, prevalence, mortality, DALYs and YLDs were estimated using all available data on mortality and stroke incidence, prevalence and excess mortality. Statistical models and country-level covariate data were employed, and all rates were age-standardized to a global population. All estimates were produced with 95% uncertainty intervals (UIs). RESULTS: In 2013, there were globally almost 25.7 million stroke survivors (71% with IS), 6.5 million deaths from stroke (51% died from IS), 113 million DALYs due to stroke (58% due to IS) and 10.3 million new strokes (67% IS). Over the 1990-2013 period, there was a significant increase in the absolute number of DALYs due to IS, and of deaths from IS and HS, survivors and incident events for both IS and HS. The preponderance of the burden of stroke continued to reside in developing countries, comprising 75.2% of deaths from stroke and 81.0% of stroke-related DALYs. Globally, the proportional contribution of stroke-related DALYs and deaths due to stroke compared to all diseases increased from 1990 (3.54% (95% UI 3.11-4.00) and 9.66% (95% UI 8.47-10.70), respectively) to 2013 (4.62% (95% UI 4.01-5.30) and 11.75% (95% UI 10.45-13.31), respectively), but there was a diverging trend in developed and developing countries with a significant increase in DALYs and deaths in developing countries, and no measurable change in the proportional contribution of DALYs and deaths from stroke in developed countries. CONCLUSION: Global stroke burden continues to increase globally. More efficient stroke prevention and management strategies are urgently needed to halt and eventually reverse the stroke pandemic, while universal access to organized stroke services should be a priority. © 2015 S. Karger AG, Basel.

The REasons for Geographic And Racial Differences in Stroke (REGARDS) Study is a national, population-based, longitudinal study of 30,000 African-American and white adults aged > or =45 years. The objective is to determine the causes for the excess stroke mortality in the Southeastern US and among African-Americans. Participants are randomly sampled with recruitment by mail then telephone, where data on stroke risk factors, sociodemographic, lifestyle, and psychosocial characteristics are collected. Written informed consent, physical and physiological measures, and fasting samples are collected during a subsequent in-home visit. Participants are followed via telephone at 6-month intervals for identification of stroke events. The novel aspects of the REGARDS study allow for the creation of a national cohort to address geographic and ethnic differences in stroke.

Population incidence of Guillain-Barré syndrome (GBS) is required to assess changes in GBS epidemiology, but published estimates of GBS incidence vary greatly depending on case ascertainment, definitions, and sample size. We performed a meta-analysis of articles on GBS incidence by searching Medline (1966-2009), Embase (1988-2009), Cinahl (1981-2009) and CABI (1973-2009) as well as article bibliographies. We included studies from North America and Europe with at least 20 cases, and used population-based data, subject matter experts to confirm GBS diagnosis, and an accepted GBS case definition. With these data, we fitted a random-effects negative binomial regression model to estimate age-specific GBS incidence. Of 1,683 nonduplicate citations, 16 met the inclusion criteria, which produced 1,643 cases and 152.7 million person-years of follow-up. GBS incidence increased by 20% for every 10-year increase in age; the risk of GBS was higher for males than females. The regression equation for calculating the average GBS rate per 100,000 person-years as a function of age in years was exp[-12.0771 + 0.01813(age in years)] × 100,000. Our findings provide a robust estimate of background GBS incidence in Western countries. Our regression model may be used in comparable populations to estimate the background age-specific rate of GBS incidence for future studies.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is relatively rare, yet the economic and social burden is substantial. Having accurate incidence and prevalence estimates would facilitate efficient allocation of healthcare resources. OBJECTIVE: To provide a comprehensive and critical review of the epidemiological literature on ALS. METHODS: MEDLINE and EMBASE (1995-2011) databases of population-based studies on ALS incidence and prevalence reporting quantitative data were analyzed. Data extracted included study location and time, design and data sources, case ascertainment methods and incidence and/or prevalence rates. Medians and interquartile ranges (IQRs) were calculated, and ALS case estimates were derived using 2010 population estimates. RESULTS: In all, 37 articles met the inclusion criteria. In Europe, the median incidence rate (/100,000 population) was 2.08 (IQR 1.47-2.43), corresponding to an estimated 15,355 (10,852-17,938) cases. Median prevalence (/100,000 population) was 5.40 (IQR 4.06-7.89), or 39,863 (29,971-58,244) prevalent cases. CONCLUSIONS: Disparity in rates among ALS incidence and prevalence studies may be due to differences in study design or true variations in population demographics such as age and geography, including environmental factors and genetic predisposition. Additional large-scale studies that use standardized case ascertainment methods are needed to more accurately assess the true global burden of ALS.

BACKGROUND: The objective of this study was to establish a prospective population-based cohort to investigate the prevalence, incidence and risk factors for mild cognitive impairment (MCI) and dementia. METHODS: The Olmsted County, Minn., population, aged 70-89 years on October 1, 2004, was enumerated using the Rochester Epidemiology Project. Eligible subjects were randomly selected and invited to participate. Participants underwent a comprehensive in-person evaluation including the Clinical Dementia Rating Scale, a neurological evaluation and neuropsychological testing. A consensus diagnosis of normal cognition, MCI or dementia was made by a panel using previously published criteria. A subsample of subjects was studied via telephone interview. RESULTS: Four hundred and two subjects with dementia were identified from a detailed review of their medical records but were not contacted. At baseline, we successfully evaluated 703 women aged 70-79 years, 769 women aged 80-89 years, 730 men aged 70-79 years and 517 men aged 80-89 years (total n = 2,719). Among the participants, 2,050 subjects were evaluated in person and 669 via telephone. CONCLUSIONS: Strengths of the study are that the subjects were randomly selected from a defined population, the majority of the subjects were examined in person, and MCI was defined using published criteria. Here, we report the design and sampling, participation, baseline measures and sample characteristics.

BACKGROUND: Stroke is a leading cause of death and disability in globally and particularly in low- and middle-income countries, and this burden is increasing. The burden of stroke pathological subtypes varies in terms of incidence, disability and mortality. Previous Global Burden of Diseases, Injuries, and Risk Factors Studies (GBD) reports did not provide separate global burden and trends estimates for haemorrhagic stroke by primary intracerebral haemorrhage (PICH) and subarachnoid haemorrhage (SAH). AIM: To summarise the GBD 2017 findings for the burden and 27-year trends for ischaemic stroke (IS), intracerebral haemorrhage and SAH by age, sex and country income level in 21 world regions and associated risk factors. METHODS: Data on stroke incidence, prevalence, mortality and disability-adjusted life-years (DALY) lost and the burden of IS, PICH and SAH were derived from all available datasets from the GBD 2017 studies. Data were analysed in terms of absolute numbers and age-standardised rates per 100,000 (95% uncertainty interval [UI]), with estimates stratified by age, sex and economic development level by the World Bank classification. We also analysed changes in the patterns of incidence, mortality and DALYs estimates between 1990 and 2017. RESULTS: In 2017, there were 11.9 million incident (95% UI 11.1-12.8), 104.2 million prevalent (98.6-110.2), 6.2 million fatal (6.0-6.3) cases of stroke and 132.1 million stroke-related DALYs (126.5-137.4). Although stroke incidence, prevalence, mortality and DALY rates declined from 1990 to 2017, the absolute number of people who developed new stroke, died, survived or remained disabled from stroke has almost doubled. The bulk of stroke burden (80% all incident strokes, 77% all stroke survivors, 87% of all deaths from stroke and 89 of all stroke-related DALYs) in 2017 was in low- to middle-income countries. Globally in 2017, IS constituted 65%, PICH -26% and SAH -9% of all incident strokes. DISCUSSION: The latest GBD estimates of stroke burden in 195 countries supersede previous GBD stroke burden findings and provide most accurate data for stroke care planning and resource allocation globally, regionally and for 195 countries. Stroke remains the second leading cause of deaths and disability worldwide. The increased stroke burden continues to exacerbate a huge pressure on people affected by stroke, their families and societies. It is imperative to develop and implement more effective primary prevention strategies to reduce stroke burden and its impact.

BACKGROUND: Hereditary cerebellar ataxias (HCA) and hereditary spastic paraplegias (HSP) are two groups of neurodegenerative disorders that usually present with progressive gait impairment, often leading to permanent disability. Advances in genetic research in the last decades have improved their diagnosis and brought new possibilities for prevention and future treatments. Still, there is great uncertainty regarding their global epidemiology. SUMMARY: Our objective was to assess the global distribution and prevalence of HCA and HSP by a systematic review and meta-analysis of prevalence studies. The MEDLINE, ISI Web of Science and Scopus databases were searched (1983-2013) for studies performed in well-defined populations and geographical regions. Two independent reviewers assessed the studies and extracted data and predefined methodological parameters. Overall, 22 studies were included, reporting on 14,539 patients from 16 countries. Multisource population-based studies yielded higher prevalence values than studies based primarily on hospitals or genetic centres. The prevalence range of dominant HCA was 0.0-5.6/10(5), with an average of 2.7/10(5) (1.5-4.0/10(5)). Spinocerebellar ataxia type 3 (SCA3)/Machado-Joseph disease was the most common dominant ataxia, followed by SCA2 and SCA6. The autosomal recessive (AR) HCA (AR-HCA) prevalence range was 0.0-7.2/10(5), the average being 3.3/10(5) (1.8-4.9/10(5)). Friedreich ataxia was the most frequent AR-HCA, followed by ataxia with oculomotor apraxia or ataxia-telangiectasia. The prevalence of autosomal dominant (AD) HSP (AD-HSP) ranged from 0.5 to 5.5/10(5) and that of AR-HSP from 0.0 to 5.3/10(5), with pooled averages of 1.8/10(5) (95% CI: 1.0-2.7/10(5)) and 1.8/10(5) (95% CI: 1.0-2.6/10(5)), respectively. The most common AD-HSP form in every population was spastic paraplegia, autosomal dominant, type 4 (SPG4), followed by SPG3A, while SPG11 was the most frequent AR-HSP, followed by SPG15. In population-based studies, the number of families without genetic diagnosis after systematic testing ranged from 33 to 92% in the AD-HCA group, and was 40-46% in the AR-HCA, 45-67% in the AD-HSP and 71-82% in the AR-HSP groups. KEY MESSAGES: Highly variable prevalence values for HCA and HSP are reported across the world. This variation reflects the different genetic make-up of the populations, but also methodological heterogeneity. Large areas of the world remain without prevalence studies. From the available data, we estimated that around 1:10,000 people are affected by HCA or HSP. In spite of advances in genetic research, most families in population-based series remain without identified genetic mutation after extensive testing. © 2014 S. Karger AG, Basel.

BACKGROUND: Head injury has been proposed as a potential modifiable risk factor for amyotrophic lateral sclerosis (ALS); however, prior studies have yielded inconsistent findings. We aimed to re-evaluate this association through an updated systematic review and meta-analysis, incorporating the latest evidence and exploring the influence of injury severity, frequency, timing, and definition. METHODS: A systematic search of PubMed, Scopus, Web of Science, Embase, EBSCO, and ProQuest from inception to January 2026 was conducted. Observational studies (cohort and case-control) reporting the association between head injury and ALS risk were included. Pooled effect estimates were generated using random-effects models. Subgroup, sensitivity, cumulative, and publication bias analyses were performed. RESULTS: Twenty-nine studies encompassing 5,033,215 participants were included. These comprised 22 case-control studies and seven cohort studies. Case-control meta-analysis showed that head injury was associated with 36% higher odds of ALS (AOR = 1.36; 95% CI: 1.24-1.48; I² = 20.4%). Cohort studies showed a positive but non-significant association (RR = 1.59; 95% CI: 0.93-2.71). Subgroup analyses showed significant associations within mild, moderate, and severe injury categories and among studies with clearly defined traumatic brain injury exposure. Single head injury was associated with higher odds of ALS (AOR = 1.22; 95% CI: 1.11-1.34). CONCLUSION: Head injury was associated with an increased risk of ALS across multiple analyses, including different injury severity levels and exposure definitions. However, the observational nature of available evidence and the possibility of reverse causation and residual confounding limit causal interpretation. Further prospective studies and mechanistic investigations are required to clarify the potential relationship between head injury and ALS development.

INTRODUCTION: As recommended in the National Institute of Neurological Disorders and Stroke TBI Classification and Nomenclature Initiative, retrospective identification of traumatic brain injury (TBI) from electronic medical record (EMR) data offers major potential for research and surveillance. Enterprise data warehouses integrating structured and unstructured EMR data could support this work, yet few studies have evaluated their use for TBI case ascertainment. This study describes a manual chart review protocol to identify acute TBI among patients receiving head CT scan from a large health system's enterprise data warehouse. METHODS: We identified encounters potentially related to TBI using clinical documentation files (e.g., Emergency Department Triage, History & Physical, Discharge Summary) within our institution's enterprise data warehouse. Two independent raters applied the protocol to 126 patients who presented in 2019 and underwent head computed tomography (CT). Sampling was limited to patients receiving a head CT scan to enrich the cohort with both TBI and non‑TBI cases. We developed a decision tree workflow to guide documentation of a plausible mechanism of head injury accompanied by clinical symptoms and/or clinically indicated neuroimaging. Criteria were adapted from the American Congress of Rehabilitation Medicine definition of mild TBI and modified for retrospective EMR data. Raters classified each case as (1) no evidence of acute TBI, (2) sufficient evidence of acute TBI, or (3) inconclusive evidence due to missing data or confounding conditions (e.g., syncope). RESULTS: Inter‑rater reliability demonstrated strong agreement across raters (88.1% agreement; Cohen's κ = 0.80 (95% CI: 0.71-0.89), p < 0.0001); inter-rater reliability was similar across subgroups of age (± 65 years), sex, and payor (government/non-government insurance). Among the 126 cases reviewed, there was agreement on sufficient evidence of acute TBI for 49 cases (86.0% agreement between rater 1 and 2), no evidence of acute TBI for 54 cases (96.4% agreement), and inconclusive evidence for 8 cases (61.5% agreement). Sensitivity analyses reweighting the sample to parent cohort marginal distributions produced similar results (94.2% agreement, κ = 0.74 (95% CI: 0.58-0.90). CONCLUSION: This manual chart review protocol showed strong inter‑rater reliability for identifying acute TBI using EMR data. Future research should examine external reliability in other health systems and compare its performance with International Classification of Diseases‑based definitions and prospective diagnosis. As enterprise data warehouses become more ubiquitous, reliable case ascertainment protocols such as this could facilitate standardized, scalable retrospective identification of TBI, supporting retrospective TBI cohort studies.

INTRODUCTION: Post-stroke epilepsy (PSE) affects 2-20% of stroke survivors. Whether post-stroke aphasia (PSA) is associated with a further increase in this risk remains unclear. This study aimed to compare PSE risk between stroke patients with and without aphasia. METHODS: Using Taiwan National Health Insurance claims data, patients aged ≥18 years hospitalized for a first stroke between 2003 and 2007 were identified. Those with and without PSA, free from epilepsy during admission or within 90 days after discharge, were followed until December 31, 2020. Propensity score-matched cohorts were also established. Cox proportional hazards models were used to estimate hazard ratios (HR) for PSE. Adjusted rate differences (aRDs) were calculated to quantify excess risk. RESULTS: With a median follow-up of 7.56 years for the PSA group (N=23,431) and 8.67 years for the non-aphasia group (N=130,058), the incidence of PSE was higher in patients with aphasia than in those without aphasia (13.02 vs. 4.56 per 1,000 person-years; aRD 2.96, 95% confidence interval [CI] 2.60-3.37). Excess risk was higher in males than in females (aRD 3.11 vs. 2.38 per 1,000 person-years), higher in younger than in older adults (aRD 3.52, 2.42, and 2.88 per 1,000 person-years in <45, 45-64, and ≥65-year groups, respectively), and higher in hemorrhagic than in ischemic stroke (3.52 vs. 2.64 per 1,000 person-years). The association was strongest during the first year after stroke and declined thereafter. CONCLUSION: Patients with post-stroke aphasia are at increased risk of epilepsy, regardless of age, sex, and stroke type.

BACKGROUND: Stroke in young adults (15-49 years) is a major public health problem in LMICs, but subtype-specific analyses and long-term projections using the latest GBD estimates remain limited. METHODS: Using GBD 2023 estimates, we assessed incidence, prevalence, deaths, and disability-adjusted life years (DALYs) for stroke and its subtypes across 129 LMICs from 1990 to 2023. Temporal trends, age- and sex-specific patterns, economic and geographic variations, health inequality, and drivers of change were evaluated. ARIMA models were used to generate trend-based projections for 2024-2045. RESULTS: From 1990 to 2023, incident and prevalent stroke cases among young adults in LMICs increased by 63% and 60%, respectively, whereas death and DALY rates declined (estimated annual percentage change [EAPC]: -0.93% and -0.92%). Intracerebral hemorrhage (ICH) remained the leading contributor to deaths and DALYs in 2023, while ischemic stroke (IS) accounted for the largest number of prevalent cases, and only IS showed increasing incidence and prevalence rates. Males generally had higher rates, with the disparity becoming more pronounced with age. Population growth was the principal driver of the rising absolute burden in low- and lower-middle-income countries, while favorable epidemiological change offset demographic pressure in upper-middle-income countries. By 2045, death and DALY rates were projected to decline further, but IS incidence and prevalence were projected to remain on an upward trend. CONCLUSION: Among young adults in LMICs, the absolute numbers of incident and prevalent stroke cases increased despite declining death and DALY rates. Prevention strategies should prioritize early-life vascular risk control, particularly for IS.

BACKGROUND: The association between transient ischemic attack (TIA) and stroke is well-established but the association with coronary heart disease (CHD) is incompletely characterized. Studying the association between TIA and CHD can also help improve risk stratification and personalized treatment strategies for patients with TIA. We undertook this analysis to determine the incidence, timing and long-term trends of post-TIA CHD and congestive heart failure (CHF) risk. METHODS: Prospective longitudinal cohort study design within the Framingham Heart Study. TIA- and CHD- free participants were matched on age and sex (ratio 3:1) to CHD-free participants with first incident TIA. The main outcomes were: 10-year risk of CHD, major CHD, CHF, and stroke comparing TIA cases with matched controls; and time trends of cardiac outcomes and stroke risk assessed in 3 epochs: 1948-1985, 1986-1999 and 2000-2019. RESULTS: 286 participants with TIA (116 (41%) men, mean age 73.1±10.8 years) were matched to 858 controls without TIA. 54 (19%) participants had CHD, 35 (12%) major CHD, 37 (13%) CHF, 83 (29%) stroke. Participants with TIA had significantly higher risk of CHD (adjusted Hazard Ratio 1.55, 95% CI (1.06-2.28 p=0.03) and stroke (adjusted HR 4.01 (2.73-5.87), p<0.0001), but not of major CHD or CHF. 35 strokes (42%) occurred within 3 months; 44 (81.5%) CHD events occurred >12 months. CHD (HR 0.64, 95% CI (0.52-0.80), p<0.0001) incidence showed a significant decline over time between 1948-2019 driven by controls; it did not decline significantly among TIA cases (HR 0.80 (0.56-1.15), p=0.22. CONCLUSIONS: We found that among patients with TIA CHD events are concentrated beyond the first year, a temporal pattern distinct from the early clustering of post-TIA stroke risk and not well captured in current post-TIA management frameworks. These findings support the need for sustained cardiovascular prevention strategies after TIA that extend beyond current pathways focused on short-term stroke risk reduction.

BACKGROUND: Multiple sclerosis (MS) is a leading cause of nontraumatic neurological disability in young and middle-aged adults, with the Nordic region exhibiting among the highest burdens globally. However, systematic comparisons of MS burden across all five Nordic countries using standardized methodologies remain scarce. METHODS: Using data from the Global Burden of Disease Study 2023, we analyzed MS burden in Denmark, Finland, Iceland, Norway, and Sweden from 1990 to 2023. Core indicators included incidence, prevalence, deaths, and disability-adjusted life years. We calculated estimated annual percentage changes (EAPCs), performed joinpoint regression to identify trend inflection points, conducted decomposition analysis to quantify drivers of burden changes, and employed Bayesian age-period-cohort models to project burden to 2050. RESULTS: From 1990 to 2023, MS burden in the Nordic region increased steadily. In 2023, age-standardized prevalence was 130.52 per 100,000 population (50,107 cases), with an EAPC of 0.9335. Incidence rose to 4.95 per 100,000 (EAPC = 0.7845), while ASDR increased modestly (EAPC = 0.2550). Finland showed the fastest growth in incidence and prevalence, whereas Sweden and Iceland exhibited stabilization after 2012 and 2014, respectively. Decomposition analysis revealed that population growth and epidemiological changes were the primary drivers of increased burden, contributing 38.39-71.08% and 23.85-71.62% to prevalence growth, respectively. Projections to 2050 indicate that prevalence will increase by 19.5%-156.01 per 100,000 (67,846 cases), with a narrowing but persistent female predominance. CONCLUSION: The rising MS burden in the Nordic region is driven primarily by population growth and epidemiological changes. Universal healthcare has enabled early access to disease-modifying therapies, sustaining low ASDR in most countries. However, aging populations and prolonged survival present emerging challenges, underscoring the need for tailored national strategies and cross-Nordic collaboration.

BACKGROUND: Huntington's disease (HD) is a rare, autosomal dominant neurodegenerative disorder caused by a CAG repeat expansion in the HTT gene. Despite its defined genetic basis, epidemiological coverage remains heterogeneous across Europe. OBJECTIVE: To assess the temporal and regional distribution of genetically confirmed HD cases in Hungary (2003-2021) and the impact of healthcare accessibility and the COVID-19 pandemic on diagnostic activity. METHODS: We analyzed 480 genetically confirmed patients (217 males, 263 females) with pathogenic HTT expansions (>36 CAG repeats). Diagnostic incidence (per 100,000 person-years) and prevalence (per 100,000 population) were calculated using national demographic data. Associations between CAG repeat length and age at onset were examined, and spatial analyses assessed regional distribution relative to specialized centers. RESULTS: Mean annual diagnostic incidence was 0.32 per 100,000 person-years and prevalence 4.73 per 100,000. Median CAG repeat length was 44 (IQR: 41-47), with median age at onset of 45 years, showing an inverse correlation (R² = 0.41, p < 0.0001). Diagnostic incidence was within the lower-to-mid European range, while prevalence was comparable to Western Europe. Regional disparities were evident, with 65% of cases within 70 km of tertiary centers. Diagnostic activity declined by ∼25% during the pandemic. CONCLUSIONS: Although the genetic and clinical characteristics of Huntington's disease in Hungary are comparable to other European populations, the observed epidemiological patterns appear to be influenced by healthcare accessibility. Inequitable access to specialized neurological services may affect case identification and diagnostic timing, and is likely to contribute to differences in epidemiological estimates in rare neurodegenerative disorders.

Introduction Ninety-day functional outcome is a strong predictor of long-term survival after stroke, but whether survival differs across calendar-year cohorts within a national stroke population at similar levels of post-stroke disability remains unclear. We therefore examined whether long-term survival from 90 days to 3 years after stroke differed between 2013 and 2020, stratified by functional outcome at 90 days. Methods In this nationwide register-based cohort study using the Swedish Stroke Register (Riksstroke), we included patients with ischemic stroke (IS) or intracerebral hemorrhage (ICH) admitted in 2013 or 2020 who were prestroke independent (mRS 0-2) and survived 90 days. The primary outcome was all-cause mortality between day 90 and 3 years after stroke. Multivariable Cox regression models estimated adjusted hazard ratios (aHRs) and assessed whether the association between calendar-year cohort and mortality differed by 90-day mRS. Results Among 27 452 patients (24 574 IS and 2 878 ICH), adjusted 3-year survival improved for 90-day survivors in 2020 compared with 2013 after IS (aHR 0.86, 95% CI 0.80-0.92), whereas no improvement was observed after ICH (aHR 0.98, 95% CI 0.80-1.19). In IS, higher survival in 2020 was observed both among functionally independent patients (mRS 0-2; aHR 0.76, 95% CI 0.68-0.86; 3-year survival 93.4% vs 91.9%) and those with dependency at 90 days (mRS 3-5; aHR 0.84, 95% CI 0.77-0.91; 76.3% vs 71.7%). In contrast, survival was not significantly different after ICH (mRS 0-2: 90.7% vs 91.1%; mRS 3-5: 78.5% vs 77.8%). Across both stroke subtypes, 90-day disability remained strongly associated with long-term mortality. Conclusion Post-90-day survival after IS was higher in the 2020 than the 2013 cohort and was observed across the full spectrum of post-stroke disability. Findings suggest that gains in survival are not limited to patients with favorable recovery but extend across levels of post-stroke disability, potentially reflecting improvements in post-acute stroke care and secondary prevention. In contrast, no corresponding improvement was observed across functional outcome levels after ICH. Further studies are needed to confirm these findings and investigate their underlying mechanisms.

INTRODUCTION: Atrial fibrillation (AF) increases the risk of anticoagulation-associated intracerebral hemorrhage (ICH), yet contemporary national mortality trends specific to this overlap remain undercharacterized. Temporal, demographic, and geographic trends in ICH mortality among patients with concomitant AF in the United States from 1999 to 2025, with projections to 2040, were examined. METHODS: A retrospective analysis of death certificate data from the Centers for Disease Control and Prevention Wide-ranging Online Data for Epidemiologic Research (CDC WONDER) database was conducted, identifying deaths listing ICH (International Classification of Diseases, Tenth Revision [ICD-10] code I61) and AF (ICD-10 code I48) in any cause-of-death field. Age-adjusted mortality rates were calculated per 100,000 population and stratified by sex, race/ethnicity, census region, and urbanization. Joinpoint regression assessed temporal trends, and autoregressive integrated moving average (ARIMA) models projected rates through 2040. RESULTS: From 1999 to 2025, 52,967 deaths were identified. The overall age-adjusted mortality rate rose from 0.4 to 0.7 per 100,000 between 1999 and 2021 (annual percent change [APC] 1.53%, p=0.016) before stabilizing through 2025. Mortality was consistently higher among men and rose significantly across the study period among Black or African American individuals (APC 1.83%, p<0.000001). Nonmetropolitan areas and the West and South regions carried the highest burden, while the Northeast declined after 2015. State rates ranged from 0.3 in Louisiana to 1.1 in Vermont, and most deaths occurred in medical facilities. CONCLUSIONS: Mortality from ICH among patients with AF rose substantially before stabilizing, with persistent disparities by sex, race, and geography. Projections through 2040 indicate stable rates but a growing absolute burden, underscoring the need for equitable hypertension control and anticoagulation management.