搜索结果：Journal of clinical neurology (Seoul, Korea)

Clinical utility and dynamics of plasma biomarkers in early-onset dementia remain underexplored. To investigate plasma biomarker trajectories and their associations with clinical outcomes in early-onset Alzheimer disease (EOAD) and frontotemporal dementia (FTD). This multicenter, prospective cohort study analyzed participants in phase 1 of the Longitudinal Study of Early-onset Dementia and Family Members (LEAF), which was conducted from April 2021 through December 2023 in 34 centers across South Korea. Patients with &#x3b2;-amyloid-positive EOAD and FTD were included and underwent annual blood sampling and clinical assessment, within a follow-up period of approximately 2 years. Data were analyzed between June 2025 and March 2026. Levels of plasma phosphorylated tau 217 (p-tau217), glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL) biomarkers were analyzed using assays. (1) Associations of baseline biomarkers with clinical outcomes (assessed with the Mini-Mental State Examination [MMSE] and the Clinical Dementia Rating-Sum of Boxes [CDR-SB] for the EOAD group, or the frontotemporal lobar degeneration [FTLD]-modified CDR-SB for the FTD group), (2) biomarker trajectories, and (3) association of biomarker level changes and clinical outcomes. A total of 322 participants with p-tau217, GFAP, and NfL analyses were stratified into the EOAD or FTD group based on their diagnosis. The EOAD group (n&#x2009;=&#x2009;245) had a mean (SD) age of 61.8 (5.4) years and included 163 females (66.5%), while the FTD group (n&#x2009;=&#x2009;77) had a mean (SD) age of 65.1 (7.3) years and included 45 females (62.3%). In the EOAD group, higher log2-transformed baseline p-tau217, GFAP, and NfL were each associated with faster decline in the MMSE score (association estimate [SE], -0.390 [0.127], P&#x2009;=&#x2009;.002; -0.775 [0.164], P&#x2009;<&#x2009;.001; and -0.679 [0.182], P&#x2009;<&#x2009;.001, respectively) and the CDR-SB score (estimate [SE], 0.401 [0.099], P&#x2009;<&#x2009;.001; 0.535 [0.126], P&#x2009;<&#x2009;.001; and 0.693 [0.122], P&#x2009;<&#x2009;.001, respectively). In the FTD group, GFAP and NfL were associated with MMSE decline (estimate [SE], -2.118 [0.566], P&#x2009;<&#x2009;.001 and -2.360 [0.428], P&#x2009;<&#x2009;.001, respectively), whereas p-tau217 was not (estimate [SE], 0.071 [0.418], P&#x2009;=&#x2009;.87). No biomarker was associated with FTLD-modified CDR-SB score change. Longitudinally, all mean (SD) biomarker levels increased in the EOAD group (p-tau217: 0.253 [0.077] pg/mL, P&#x2009;=&#x2009;.001; GFAP: 0.173 [0.040] pg/mL, P&#x2009;<&#x2009;.001; NfL: 0.149 [0.045] pg/mL, P&#x2009;=&#x2009;.001), whereas in the FTD group, only NfL level showed an upward pattern (0.251 [0.127] pg/mL, P&#x2009;=&#x2009;.05). Annualized biomarker changes were associated with worsening clinical outcomes in the EOAD group, but not in the FTD group. GFAP and NfL level increases were associated with MMSE score decline (estimate [SE], -0.005 [0.002], P&#x2009;=&#x2009;.007 and -0.010 [0.003], P&#x2009;=&#x2009;.001, respectively), while p-tau217 level increases were associated with CDR-SB score worsening (estimate [SE], 0.072 [0.024], P&#x2009;=&#x2009;.003) in the EOAD group. In this cohort study of patients with EOAD and FTD, baseline p-tau217, GFAP, and NfL were consistently associated with clinical outcomes in the EOAD group, whereas GFAP and NfL were associated with cognition only in the FTD group. These findings demonstrate distinct characteristics of plasma biomarkers in EOAD and FTD, supporting their potential utility for risk stratification.

ADSS1 myopathy (previously referred to as ADSSL1 myopathy) is a rare autosomal recessive muscle disease caused by mutations in the ADSS1 gene, which encodes an enzyme critical for purine nucleotide synthesis. First characterized in Korean patients in 2016, the disease exhibits phenotypic variability in its clinical presentation. We conducted a retrospective cohort study of 30 patients with genetically confirmed ADSS1 myopathy (18 males and 12 females) at Gangnam Severance Hospital from 2002 to 2024. The patients were classified into proximal-onset (n&#x2009;=&#x2009;9) and distal-onset (n&#x2009;=&#x2009;20) groups based on the location of initial muscle weakness, with one patient presenting with isolated hyperCKemia. Clinical assessments, genetic analyses, and muscle MRI were performed on 10 patients to evaluate clinical-radiological correlations. The median age at symptom onset was 8.0 years [Interquartile range (IQR): 7.0-14.0] with a median disease duration of 24.0 years [IQR: 17.0-34.0]. The most common initial symptoms were slow running (66.7%), early fatigue (16.7%), and gait disturbances (10.0%). Facial involvement was observed in 80.0% of the patients and oropharyngeal dysfunction in 56.7%. The median serum creatine kinase level was 214.0 IU/L [IQR: 125.0-394.0]. Genetic analysis revealed five pathogenic ADSS1 variants, with c.781G&#x2009;>&#x2009;A (51.7% of alleles) and c.919del (40.0% of alleles) being the most prevalent. Most patients (73.3%) were compound heterozygous for the two variants. Despite the clinical heterogeneity between the proximal- and distal-onset groups, none of the clinical differences were statistically significant. Muscle MRI revealed a remarkably consistent pattern of preferential involvement of the distal lower limb muscles, particularly the gastrocnemius and soleus muscles, regardless of the initial clinical presentation. This study, which represents the largest Korean ADSS1 myopathy cohort to date, highlights the striking discordance between clinical phenotypes and radiological findings. Although the clinical presentations varied considerably, MRI revealed consistent distal dominant muscle involvement patterns across all patients. This suggests that the underlying pathological process follows a predictable anatomical distribution independent of the initial symptomatic muscle groups. Our findings support the utility of muscle MRI as a valuable diagnostic tool for ADSS1 myopathy and suggest its conceptualization as a unified disease entity with a common pathophysiological mechanism involving selective muscle vulnerability based on metabolic requirements.

Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as non-alcoholic fatty liver disease, is one of the most prevalent liver diseases globally, contributing to both economic and health-related challenges. We aimed to evaluate the global, regional, and national burden of MASLD from 1990 to 2023, quantify the contribution of identified modifiable risk factors, and project future prevalence up to the year 2050. Estimates of MASLD prevalence and disability-adjusted life-years (DALYs) were produced by age, sex, region, Socio-demographic Index (SDI), and Healthcare Access and Quality (HAQ) index across 204 countries and territories from 1990 to 2023 as part of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023. The MASLD burden attributable to three risk factors (smoking, high BMI, and high fasting plasma glucose) was assessed as part of the GBD comparative risk assessment. As a secondary analysis, we used these estimates to forecast MASLD prevalence up to 2050 using fasting plasma glucose and mean BMI as predictors. Furthermore, to examine the relative contributions of population ageing, population growth, and changes in MASLD prevalence rate to the forecasted changes in case counts from 2023 to 2050, we conducted a decomposition analysis. In 2023, approximately 1&#xb7;3 billion (95% uncertainty interval [UI] 1&#xb7;2 to 1&#xb7;4) individuals were estimated to be living with MASLD (ie, 16&#xb7;1% of the global population), with an age-standardised prevalence rate of 14&#x2009;429&#xb7;3 (95% UI 13&#x2009;268&#xb7;3 to 15&#x2009;990&#xb7;6) per 100&#x2009;000 population, representing a percentage increase of 142&#xb7;7% (95% UI 139&#xb7;2 to 146&#xb7;7) in crude numbers from 1990 (0&#xb7;5 billion [0&#xb7;5 to 0&#xb7;6]) and of 28&#xb7;6% (27&#xb7;8 to 29&#xb7;5) in the rate (11&#x2009;217&#xb7;2 [10&#x2009;276&#xb7;8 to 12&#x2009;467&#xb7;0] per 100&#x2009;000 in 1990). An estimated 3&#xb7;6 million (2&#xb7;8 to 4&#xb7;5) total DALYs were attributable to MASLD worldwide in 2023, corresponding to an age-standardised DALY rate of 39&#xb7;6 (31&#xb7;2 to 49&#xb7;9) per 100&#x2009;000 population. Despite a 116&#xb7;3% (93&#xb7;3 to 139&#xb7;4) increase in crude DALYs (from 1&#xb7;7 million [1&#xb7;3 to 2&#xb7;1] in 1990), its age-standardised estimate remained consistent (1&#xb7;8% [-8&#xb7;6 to 12&#xb7;8]) from 1990 (38&#xb7;9 [30&#xb7;1 to 49&#xb7;8] per 100&#x2009;000) to 2023. There was substantial variation in age-standardised estimates across regions. North Africa and the Middle East had the highest prevalence rate (29&#x2009;246&#xb7;1 [26&#x2009;848&#xb7;3 to 32&#x2009;048&#xb7;7] per 100&#x2009;000) and Andean Latin America showed the highest DALY rate (152&#xb7;3 [114&#xb7;1 to 194&#xb7;7] per 100&#x2009;000). By contrast, the high-income Asia Pacific region had the lowest prevalence rate (8653&#xb7;5 [7923&#xb7;7 to 9592&#xb7;8] per 100&#x2009;000) and east Asia had the lowest DALY rate (16&#xb7;3 [13&#xb7;5 to 19&#xb7;9] per 100&#x2009;000) among all GBD regions. North Africa and the Middle East showed disproportionately higher prevalence rates relative to other regions with similar SDIs. Lower SDIs and HAQs were associated with higher age-standardised DALY rates. The age-standardised prevalence rate was consistently higher in males (15&#x2009;616&#xb7;4 [14&#x2009;349&#xb7;2 to 17&#x2009;263&#xb7;3] per 100&#x2009;000 people in 2023) than in females (13&#x2009;245&#xb7;2 [12&#x2009;132&#xb7;0 to 14&#x2009;692&#xb7;6] per 100&#x2009;000 people), and peaked at age 80-84 years in both sexes. The number of MASLD prevalent cases was the highest in younger adults, peaking at age 35-39 years for males and age 55-59 years for females. Among the risk factors for MASLD, high fasting plasma glucose presented the largest contribution to the age-standardised DALY rate of total MASLD in 2023 (2&#xb7;2 [95% UI 1&#xb7;6 to 3&#xb7;1] per 100&#x2009;000 people), followed by high BMI (1&#xb7;4 [0&#xb7;6 to 2&#xb7;4] per 100&#x2009;000 people) and smoking (1&#xb7;0 [0&#xb7;3 to 1&#xb7;8] per 100&#x2009;000 people). Our forecasting model estimates that 1&#xb7;8 billion (95% UI 1&#xb7;6 to 2&#xb7;0) individuals are likely to have MASLD by 2050, representing a 42&#xb7;0% increase from 2023. The age-standardised prevalence rate is expected to increase to 15&#x2009;774&#xb7;9 (95% UI 14&#x2009;613&#xb7;9 to 17&#x2009;336&#xb7;2) per 100&#x2009;000 people in 2050, representing an average annual percentage change of 0&#xb7;3% (95% UI 0&#xb7;3-0&#xb7;3). According to our decomposition analysis, this change will be primarily due to population growth, particularly in sub-Saharan Africa and North Africa and Middle East, and less by population ageing or epidemiological change. With a global prevalence of 16&#xb7;1% and approximately 1&#xb7;3 billion people already living with MASLD in 2023, the condition has and will continue to have substantial health and economic impacts worldwide. An inverse association between the HAQ Index and age-standardised DALY rates suggests that countries with lower health-care access and quality might be less well positioned to manage the growing MASLD burden, underscoring the need for strengthened health-system capacity in these settings. Gates Foundation.

Breast cancer is a leading cause of mortality and morbidity among females worldwide. As part of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023, we provided an updated comprehensive assessment of the epidemiological trends, disease burden, and risk factors associated with breast cancer globally, regionally, and nationally from 1990 to 2023. Breast cancer incidence, mortality, prevalence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs) were estimated by age and sex for 204 countries and territories from 1990 to 2023. Mortality estimates were generated using GBD Cause of Death Ensemble models, leveraging data from population-based cancer registration systems, vital registration systems, and verbal autopsies. Mortality-to-incidence ratios were calculated to derive both mortality and incidence estimates. Prevalence was calculated by combining incidence and modelled survival estimates. YLLs were established by multiplying age-specific deaths with the GBD standard life expectancy at the age of death. YLDs were estimated by applying disability weights to prevalence estimates. The sum of YLLs and YLDs equalled the number of DALYs. Breast cancer burden attributable to seven risk factors was examined through the comparative risk assessment framework. The GBD forecasting framework was used to forecast breast cancer incidence and mortality from 2024 to 2050. Age-standardised rates were calculated for each metric using the GBD 2023 world standard population. In 2023, there were an estimated 2&#xb7;30 million (95% uncertainty interval [UI] 2&#xb7;01 to 2&#xb7;61) breast cancer incident cases, 764&#x2008;000 deaths (672&#x2008;000 to 854&#x2008;000), and 24&#xb7;1 million (21&#xb7;3 to 27&#xb7;5) DALYs among females globally. In the World Bank low-income group, where a low age-standardised incidence rate (ASIR) was estimated (44&#xb7;2 per 100&#x2008;000 person-years [31&#xb7;2 to 58&#xb7;4]), the age-standardised mortality rate (ASMR) was the highest (24&#xb7;1 per 100&#x2008;000 [16&#xb7;8 to 31&#xb7;9]). The highest ASIR was in the high-income group (75&#xb7;7 per 100&#x2008;000 [67&#xb7;1 to 84&#xb7;0]), and the lowest ASMR was in the upper-middle-income group (11&#xb7;2 per 100&#x2008;000 [10&#xb7;2 to 12&#xb7;3]). Between 1990 and 2023, the ASIR in the low-income group increased by 147&#xb7;2% (38&#xb7;1 to 271&#xb7;7), compared with a 1&#xb7;2% (-11&#xb7;5 to 17&#xb7;2) change in the high-income group. The ASMR decreased in the high-income group, changing by -29&#xb7;9% (-33&#xb7;6 to -25&#xb7;9), but increased by 99&#xb7;3% (12&#xb7;5 to 202&#xb7;9) in the low-income group. The increase in age-standardised DALY rates followed that of ASMRs. Risk factors such as dietary risks, tobacco use, and high fasting plasma glucose contributed to 28&#xb7;3% (16&#xb7;6 to 38&#xb7;9) of breast cancer DALYs in 2023. The risk factors with a decrease in attributable DALYs between 1990 and 2023 were high alcohol use and tobacco. By 2050, the global incident cases of breast cancer among females were forecast to reach 3&#xb7;56 million (2&#xb7;29 to 4&#xb7;83), with 1&#xb7;37 million (0&#xb7;841 to 2&#xb7;02) deaths. The stable incidence and declining mortality rates of female breast cancer in high-income nations reflect success in screening, diagnosis, and treatment. In contrast, the concurrent rise in incidence and mortality in other regions signals health system deficits. Without effective interventions, many countries will fall short of the WHO Global Breast Cancer Initiative's ambitious target of achieving an annual reduction of 2&#xb7;5% in age-standardised mortality rates by 2040. The mounting breast cancer burden, disproportionately affecting some of the world's most vulnerable populations, will further exacerbate health inequalities across the globe without decisive immediate action. Gates Foundation, St Jude Children's Research Hospital.

Restless legs syndrome (RLS) shows substantial heterogeneity in symptoms, comorbidity, and treatment response. This study aimed to identify clinically meaningful phenotypic subgroups of idiopathic RLS using an unsupervised, data-driven clustering and to evaluate associations with longitudinal clinical outcomes. We retrospectively analyzed 360 patients with idiopathic RLS who had &#x2265;1 year of follow-up. Hierarchical agglomerative clustering based on Gower distance was performed using seven baseline variables selected a priori: onset age, sex, family history of RLS, International RLS rating scale (IRLS) score, painful RLS sensations, psychiatric comorbidity, and serum ferritin. Four distinct phenotypic clusters were identified: (1) late-onset RLS in women without family history, (2) painful RLS phenotype, (3) late-onset RLS in men without family history, and (4) early-onset familial RLS. Overall RLS severity, as measured by IRLS, did not differ significantly across clusters. During the follow-up, the painful RLS phenotype showed more frequent daytime symptoms, greater opioid use, and a higher proportion of refractory course than the late-onset female phenotype. Among late-onset patients, women reported more psychiatric symptoms and poorer sleep-related quality of life than men despite comparable RLS severity. The early-onset familial phenotype also demonstrated relatively frequent opioid use, despite the absence of baseline painful symptoms. Unsupervised clustering identified four clinically interpretable phenotypes of idiopathic RLS distinguished primarily by onset age, family history, painful sensations, and sex. These phenotypes, defined by baseline clinical characteristics, were associated with differences in longitudinal treatment patterns and disease course, supporting a phenotype-informed RLS management.

Optimal clinical application of the minimal clinically important difference (MCID) for the MMN-Rasch-built Overall Disability Scale&#xa9; (MMN-RODS) scale is unknown. We retrospectively studied subjects with MMN from 2 UK&#xa0;neuropathy centres. Raw and centile MMN-RODS scores were collected, at initial, two intermediate, and latest assessment, and distribution-based MCIDs determined at studied time-points. The sensitivities of raw, centile and individualised MCIDs, were compared. We included 32 consecutive subjects with MMN on individualised immunoglobulin dosing regimens. First intermediate, second intermediate, and latest assessments were performed at a median of 17.0, 54.1 and 74.6&#xa0;months from onset, respectively. Progressive amelioration of mean raw MMN-RODS score occurred between initial and latest assessment. The distribution-based raw MMN-RODS MCID was of 3, 4 and 5, and the distribution-based centile MMN-RODS MCID was of 6, 7 and 7, at first intermediate, second intermediate and latest assessment, respectively. At first intermediate assessment, raw and individualised MCIDs were equally sensitive, and both more sensitive than centile MCID (McNemar's Test: p&#x2009;<&#x2009;0.001, p&#x2009;<&#x2009;0.001). Raw MCID, centile MCID and individualised MCID, all had equivalent sensitivity at the second intermediate and latest assessment. Neither initial MMN-RODS score, nor amplitude of treatment-induced changes in early disease stages, independently predicted total improvement amplitude or final outcome. MMN-RODS MCID cut-offs may require adaption to assessment timing. In earlier stages, raw/individualised MCID may be more sensitive than centile MCID, whereas all three methods may subsequently be equivalent. Initial disability and early treatment response do not predict achievable total improvement amplitude nor final outcome.

Consciousness is central to the human condition, but its inherent characteristics and underlying mechanisms remain poorly understood. Advances in neuroscience based on the concept of the vegetative state have expanded the understanding of disorders of consciousness (DoC), particularly the minimally conscious state (MCS) and emergence from the MCS. Despite this progress, diagnostic uncertainty persists due to the subtlety of clinical signs and variable outcomes. Although standardized behavioral scales remain the gold standard for diagnosing DoC, advanced imaging and electrophysiological tools increasingly highlight the importance of multimodal assessments. These approaches have demonstrated that patients who appear unresponsive in behavioral assessments may voluntarily engage in mental activities that can be detected using functional magnetic resonance imaging and electroencephalography, potentially revealing covert consciousness and suggesting possible therapeutic strategies. This review consolidates the current evidence on the diagnosis, prognosis, and mechanisms of DoC across various neurological conditions. We highlight the role of brain networks in producing diverse phenotypes as well as the need for well-designed studies that can improve multimodal diagnostic strategies. Building on recent initiatives aimed at standardizing definitions, prognostic guidelines, data collection, and clinical management practices, we show that further multimodal neuroimaging research is essential to improving diagnoses, prognostication, and outcomes for patients with DoC and their families.

Blood pressure (BP) management following successful reperfusion after endovascular thrombectomy (EVT) is critical in achieving favorable clinical outcomes. Individualized BP management using predictive modeling by machine learning may further improve prediction of functional outcomes. This study was a retrospective analysis of data from the Outcome in Patients Treated with Intra-Arterial Thrombectomy-Optimal Blood Pressure Control (OPTIMAL-BP) trial, a randomized controlled trial comparing between intensive and conventional BP management during the 24&#xa0;h after successful recanalization by EVT from June 18, 2020, to November 28, 2022. The trial was conducted across 19 centers in South Korea. Machine learning models were developed to predict functional independence (90-day modified Rankin Scale 0 to 2). Model performance was compared between clinical variables only and systolic blood pressure (SBP) metrics in addition to clinical variables. In addition, the Shapley additive explanations (SHAP) analysis was performed to provide model explanation and understand the importance of SBP metrics. A total of 288 patients (61.1% men, median age 75 years [interquartile range, 65-81]) were included. Among the six algorithms, the deep neural network model incorporating SBP metrics performed best on validation, achieving an area under the curve of 0.86 (95% confidence interval, 0.76-0.92) which was significantly better than the model using only clinical variables (area under the curve 0.80 [95% confidence interval, 0.69-0.88], P = .037). Among SBP metrics, SHAP analysis identified time rate of SBP and minimum SBP as important features, with time rate showing greater influence in the intensive group and minimum SBP in the conventional group. Integrating SBP metrics with clinical variables significantly improved machine learning performance in predicting functional outcomes after successful EVT. Explainable artificial intelligence (AI) identified time rate and minimum SBP as key predictors of outcome. Trial Registration Information: ClinicalTrials.gov (NCT04205305; registered December 17, 2019).

Central disorders of hypersomnolence (CDH) significantly impair quality of life, yet the burden of depressive symptoms across their subtypes remains poorly understood. We aimed to examine the clinical profiles and risk factors for depression burden among patients with narcolepsy type 1 (NT1), narcolepsy type 2 (NT2), and idiopathic hypersomnia (IH). We included 171 patients from 11 tertiary sleep centers in South Korea and 69 patients with CDH from Seoul National University Hospital. We analyzed data from polysomnography and the multiple sleep latency test. Depression burden was assessed using the Beck Depression Inventory-II (BDI-II) or Patient Health Questionnaire-9 (PHQ-9) (n&#xa0;=&#xa0;119). Multivariable logistic regression was performed to identify independent risk factors for depression burden. The prevalence of depression burden (BDI-II &#x2265;16 or PHQ-9&#xa0;&#x2265;&#xa0;10) and clinical insomnia (Insomnia Severity Index &#x2265;15) were 52.9% and 38.7%, respectively. The risk of depression burden was most pronounced in patients with IH (63.9%), whereas the NT2 group (36.7%) showed a significantly lower risk (OR 0.26; 95% CI 0.09-0.78, with IH as the reference). Clinical insomnia (OR 5.08; 95% CI 2.10-12.29), and young adults aged 19-29&#xa0;years (OR 3.12; 95% CI 1.02-9.86) were significant risk factors for depression burden. More than half of patients with CDH experience a substantial depressive burden, which is most prominent in those with IH. These findings highlight the importance of regular psychiatric screening and integrated multidisciplinary care to improve clinical outcomes and quality of life.

Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) has been increasingly recognized, yet concerns remain regarding the overuse and misinterpretation of MOG-IgG testing. The recently published MOGAD diagnostic criteria emphasize selective testing and rigorous interpretation in the context of compatible clinical syndromes and supportive features. We investigated, in real-world practice, the extent to which these criteria are appropriately applied and the frequency and characteristics of their misapplication at a referral center. We retrospectively reviewed patients referred to the National Cancer Center with externally reported MOG-IgG positivity between January 2021 and December 2024. External assay results were based on laboratory-specific cutoffs, which had not been verified against clinically validated thresholds. Final diagnoses were determined by expert consensus after comprehensive evaluation, applying the 2023 international MOGAD diagnostic criteria. Fifty-seven patients with external MOG-IgG positivity were referred, of whom 48 (84.2%) had been labeled as MOGAD. Upon re-evaluation, only 39 patients (68.4%) met the diagnostic criteria. Of the 18 non-confirmed patients, 5 (27.8%) manifested nonspecific symptoms incompatible with core demyelinating events, 9 patients (50.0%) received an alternative diagnosis, and 4 (22.2%) presented core events but lacked supportive features. Over one-third of patients with externally reported positive results did not meet diagnostic criteria, illustrating the risk of non-targeted MOG-IgG testing and overinterpretation of antibody results. Selective test utilization and strict adherence to diagnostic criteria in the context of appropriate clinical syndromes and supportive findings are essential to prevent overdiagnosis and inappropriate treatment.

Spinal and bulbar muscular atrophy (SBMA) is a rare X-linked neuromuscular disorder characterized by slowly progressive motor decline. However, there is no specific fluid marker that reflects the severity or progression of the disease. Therefore, identifying measurable markers that reflect disease progression remains a major unmet need in SBMA management. Plasma samples from 21 Korean patients with SBMA were collected at baseline and after 3 years. Untargeted and targeted metabolomics profiling was performed, and plasma sphingosine-1-phosphate (S1P) was the final candidate biomarker. S1P was then quantified using liquid chromatography-mass spectrometry. Associations between longitudinal S1P changes and clinical parameters, including the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R), serum creatine kinase (CK), 6-minute walk test (6MWT), and forced vital capacity (FVC), were examined. Plasma S1P levels significantly declined in the fast progression group over 3 years, while remaining relatively stable in the slow progression group. Longitudinal changes in plasma S1P showed weak-to-moderate positive trends with clinical measurements, including ALSFRS-R, FVC, and 6MWT, and a negative trend with serum CK at follow-up. Plasma S1P represents a promising quantitative biomarker for monitoring SBMA progression. Validation in larger cohorts and mechanistic studies of S1P regulation are warranted to establish its role in clinical management.

Body pain significantly affects the quality of life. However, the relationship between headache and pain across broad body regions remains unclear. This population-based cross-sectional study aimed to investigate the prevalence and impact of body pain in migraine and tension-type headache (TTH). We analyzed baseline data from 2,548 participants in the Korean population-based Circannual Change in Headache and Sleep study. Participants were classified into migraine (n&#x2009;=&#x2009;145), TTH (n&#x2009;=&#x2009;805), and no-headache (n&#x2009;=&#x2009;920) groups. Body pain was assessed across 19 regions using the Widespread Pain Index (WPI). Multivariable analyses adjusted for age, sex, and psychiatric symptoms were performed. Body pain was more widespread in the migraine and TTH than in the no-headache group, showing a gradient of migraine&#x2009;>&#x2009;TTH&#x2009;>&#x2009;no-headache (P&#x2009;<&#x2009;0.001). Migraine was most strongly associated with neck pain (odds ratio [OR] 2.84, P&#x2009;=&#x2009;0.008), whereas TTH showed the strongest association with upper back pain (OR 2.74, P&#x2009;=&#x2009;0.008). Higher WPI and body-pain intensity were associated with higher headache intensity, more monthly headache days, more monthly severe headache days, and higher HIT-6 scores, as well as poorer quality of life and greater depression, anxiety, and insomnia (all P&#x2009;<&#x2009;0.001). Axial body pain was associated with higher monthly headache days in migraine, whereas upper body pain was associated with higher monthly headache/severe headache days in TTH. Body pain is more prevalent and widespread in patients with migraine and TTH and is associated with a greater disease burden, potentially reflecting central sensitization. Distinct patterns of regional pain, particularly neck pain in migraine and upper back pain in TTH, may provide clinically relevant insights into underlying nociceptive mechanisms.

Cognitive reserve has been shown to modulate the onset and progression of Alzheimer disease (AD) symptoms. Although its role in sporadic AD is well-studied, how cognitive reserve influences the timing and progression of symptoms in dominantly inherited AD (DIAD) remains unclear. This study aimed to quantify cognitive reserve in DIAD carriers and test whether higher cognitive reserve is associated with later symptom onset and slower functional decline. We analyzed data from the Dominantly Inherited Alzheimer's Network study. Cognitive reserve was modeled using a residual-based latent variable approach, decomposing cognitive performance into demographic (CogD), biomarker (CogB), and reserve or residual (CogR) components. Primary outcomes were age at clinical symptom onset (CDR >0) and longitudinal change in the Clinical Dementia Rating-Sum of Boxes (CDR-SBs). Data were analyzed using Cox proportional hazards models and linear mixed-effects models, adjusting for estimated years from onset (EYO). A total of 710 Dominantly Inherited Alzheimer Network (DIAN) participants were included in the analysis, comprising 271 non-DIAD carriers (nMC), 284 asymptomatic DIAD carriers (aMC), and 155 symptomatic DIAD carriers. In asymptomatic carriers, using a zero-inflation model adjusted for EYO showed that a 1 SD increase in the reserve component (CogR) was associated with a 4.06-fold increase in the odds of being clinically unimpaired (CDR-SB = 0; 95% CI 1.84-8.95). Similarly, a 1 SD increase in the demographic (CogD) and biomarker (CogB) components increased the odds of being CDR-SB = 0 by 2.60 (95% CI 1.10-6.16) and 5.16 (95% CI 2.00-13.33), respectively. Among symptomatic carriers, only the reserve and the biomarker components were significant. A 1 SD increase in CogR was associated with a 0.81-fold reduction in baseline CDR-SB score (95% CI 0.72-0.92), and a 1 SD increase in CogB was associated with a 0.60-fold reduction in CDR-SB (95% CI 0.50-0.71). Our findings indicate that higher cognitive reserve values are associated with delayed conversion to mild cognitive impairment and slower progression on clinical dementia rating scales. These findings suggest that cognitive reserve plays a protective role in modifying the clinical trajectory of genetically determined AD.

Information on childhood cancer burden is crucial for effective cancer policy planning. Unfortunately, observed paediatric cancer data are not available in every country, and previous global burden estimates have not discretely reported several common cancers of childhood. We aimed to inform efforts to address childhood cancer burden globally by analysing results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023, which now include nine additional cancer causes compared with previous GBD analyses. GBD 2023 data sources for cancer estimation included population-based cancer registries, vital registration systems, and verbal autopsies. For childhood cancers (defined as those occurring at ages 0-19 years), mortality was estimated using cancer-specific ensemble models and incidence was estimated using mortality estimates and modelled mortality-to-incidence ratios (MIRs). Years of life lost (YLLs) were estimated by multiplying age-specific cancer deaths by the standard life expectancy at the age of death. Prevalence was estimated using survival estimates modelled from MIRs and multiplied by sequelae-specific disability weights to estimate years lived with disability (YLDs). Disability-adjusted life-years (DALYs) were estimated as the sum of YLLs and YLDs. Estimates are presented globally and by geographical and resource groupings, and all estimates are presented with 95% uncertainty intervals (UIs). Globally, in 2023, there were an estimated 377&#x2008;000 incident childhood cancer cases (95% UI 288&#x2008;000-489&#x2008;000), 144&#x2008;000 deaths (131&#x2008;000-162&#x2008;000), and 11&#xb7;7 million (10&#xb7;7-13&#xb7;2) DALYs due to childhood cancer. Deaths due to childhood cancer decreased by 27&#xb7;0% (15&#xb7;5-36&#xb7;1) globally, from 197&#x2008;000 (173&#x2008;000-218&#x2008;000) in 1990, but increased in the WHO African region by 55&#xb7;6% (25&#xb7;5-92&#xb7;4), from 31&#x2008;500 (24&#x2008;900-38&#x2008;500) to 49&#x2008;000 (42&#x2008;600-58&#x2008;200) between 1990 and 2023. In 2023, age-standardised YLLs due to childhood cancer were inversely correlated with country-level Socio-demographic Index. Childhood cancer was the eighth-leading cause of childhood deaths and the ninth-leading cause of DALYs among all cancers in 2023. The percentage of DALYs due to uncategorised childhood cancers was reduced from 26&#xb7;5% (26&#xb7;5-26&#xb7;5) in GBD 2017 to 10&#xb7;5% (8&#xb7;1-13&#xb7;1) with the addition of the nine new cancer causes. Target cancers for the WHO Global Initiative for Childhood Cancer (GICC) comprised 47&#xb7;3% (42&#xb7;2-52&#xb7;0) of global childhood cancer deaths in 2023. Global childhood cancer burden remains a substantial contributor to global childhood disease and cancer burden and is disproportionately weighted towards resource-limited settings. The estimation of additional cancer types relevant in childhood provides a step towards alignment with WHO GICC targets. Efforts to decrease global childhood cancer burden should focus on addressing the inequities in burden worldwide and support comprehensive improvements along the childhood cancer diagnosis and care continuum. St Jude Children's Research Hospital, Gates Foundation, and St Baldrick's Foundation.

Meningitis remains the leading infectious cause of neurological disabilities globally, disproportionately affecting children younger than 5 years and populations in the African meningitis belt. Whereas previous global estimates focused on ten pathogen categories, this study presents the most comprehensive analysis to date, assessing the meningitis burden attributable to 17 causative pathogens based on the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023 framework. GBD is a systematic, scientific effort aimed at quantifying the comparative magnitude of health loss caused by diseases, injuries, and risk factors across age groups, sexes, and geographical locations over time. We estimated meningitis mortality using the Cause of Death Ensemble model (CODEm) and morbidity using DisMod-MR 2.1, incorporating data from vital registration, verbal autopsy, surveillance, hospital data, and systematic reviews. Aetiology-specific estimates were generated with pathogen-linked case-fatality ratios and splined binomial regression models. Risk factor attribution was based on established risk-outcome pairs and population attributable fractions. In 2023, there were 259&#x2009;000 (95% uncertainty interval 202&#x2009;000-335&#x2009;000) global deaths and 2&#xb7;54 million (2&#xb7;20-2&#xb7;93) incident cases of meningitis. Children younger than 5 years accounted for more than a third of deaths (86&#x2009;600 [53&#x2009;300-149&#x2009;000]). Streptococcus pneumoniae, Neisseria meningitidis, non-polio enteroviruses, and other viruses were the leading causes of death, while non-polio enteroviruses caused the most cases. The four WHO-defined preventable meningitis pathogens of interest (S pneumoniae, N meningitidis, Haemophilus influenzae, and Group B streptococcus) contributed to 98&#x2009;700 deaths (77&#x2009;000-127&#x2009;000) and 594&#x2009;000 cases (514&#x2009;000-686&#x2009;000). Low birthweight, short gestation, and household air pollution were the top risk factors for meningitis-related mortality. Although mortality and incidence have declined significantly since 1990, progress is insufficient to meet WHO 2030 targets. Despite marked progress in reducing bacterial meningitis via global vaccination campaigns, a substantial meningitis burden persists, attributable both to common pathogens such as S pneumoniae and N meningitidis and to emerging non-bacterial pathogens such as Candida spp and drug-resistant fungi. Achieving WHO goals will require sustained investment in surveillance, vaccination, maternal screening, and health-system strengthening, especially in high-burden settings. Gates Foundation, Wellcome Trust, and UK Department of Health and Social Care.

Poststroke dysarthria, a common speech impairment, affects up to half of all stroke survivors, often reducing their ability to communicate, and adversely affecting their quality of life. Although conventional speech therapy for poststroke dysarthria is effective, access is often limited by time and geographical constraints. Here, digital speech therapy may serve as a remotely deliverable alternative for selected patients. However, few trials have assessed its efficacy, safety, and usability. This study aimed to evaluate whether a smartphone-based speech therapy app is noninferior to conventional workbook-based therapy in improving speech intelligibility among individuals with poststroke dysarthria. This single-blind, randomized controlled, noninferiority trial was performed at 3 hospitals in South Korea. Adults (&#x2265;19 y) with poststroke dysarthria who were cognitively intact, without aphasia, and able to use a smartphone were eligible. Participants were enrolled between July 20, 2023, and April 15, 2024. Participants were randomly assigned (1:1), stratified by stroke phase, using a block randomization method, to receive either a smartphone-based digital therapy app or a conventional workbook-based therapy for 4 weeks. The primary outcome was speech intelligibility (0-100 perceptual rating) after the intervention. Primary analysis was intention-to-treat using analysis of covariance. A noninferiority margin of 19 points was pre-defined. A total of 73 participants were enrolled (median age 62.00 years). Among them, 38 were assigned to the digital speech therapy group and 35 to the control group. Intelligibility scores improved from 80.48 (SD 18.92) to 92.08 (SD 12.38) in the intervention group, and from 80.94 (SD 16.74) to 88.11 (SD 18.06) in the control group. The adjusted between-group difference was 4.49 (95% CI 0.61-8.37), and the lower bound of the 95% CI was above the prespecified noninferiority margin (-19), which supported noninferiority. No significant between-group differences were observed in the secondary outcomes related to speech function or psychological status. The system usability score was 89.6, and adherence in the digital speech therapy group was 64.6% based on app logs, with no treatment-related adverse events. Digital speech therapy was noninferior to conventional workbook-based therapy in improving speech intelligibility and was feasible across acute to early subacute and chronic stroke phases in cognitively intact stroke survivors with predominantly mild-to-moderate dysarthria. However, feasibility and efficacy in older stroke survivors with cognitive deficits or co-occurring aphasia, or in those unable to use smartphones, remain to be established.

This study aims to evaluate the global burden of adverse effects of medical treatment (AEMT) using data from the Global Burden of Disease Study (GBD) 2021. Data were extracted from the GBD 2021, covering 204 countries/territories from 1990 to 2021. AEMT was defined using ICD-9 and ICD-10 codes, encompassing complications from medical procedures, treatments, or healthcare exposures. Estimates were categorized into fatal and non-fatal outcomes and stratified by age, sex, year, and covariates, including the Socio-demographic Index (SDI). Mortality-incidence ratios (MIRs), defined as the ratio of mortality calculated by dividing the number of deaths by the total incident cases, were analyzed. In 2021, the global age-standardized prevalence, incidence, disability-adjusted life years (DALYs), and mortality rates of AEMT were 11.48 (95% uncertainty interval [UI], 8.86-14.13), 150.44 (131.19-171.81), 64.19 (51.06-73.11), and 1.53 (1.29-1.68) per 100,000 population, respectively. DALY rates were highest in the early neonatal group (4,789.47 per 100,000 population [95% UI, 3,682.00-5,963.30]), while mortality rates followed a U-shaped pattern across age groups. In 2021, MIRs were highest at both ends of the age range: the early neonatal group (0.58 [95% UI, 0.55-0.58]) and the 95+ age group (0.05 [0.04-0.06]). This pattern was consistent across all SDI quintiles, with higher MIRs observed in lower SDI quintiles. The significantly higher prevalence and incidence rates of AEMT among the older population in high SDI quintiles, compared to lower SDI quintiles, could be attributed to the healthcare overutilization, highlighting the need for policy adjustments.

BackgroundWoohwangchungsimwon (WCW) is a traditional Korean herbal formula commonly used to treat anxiety and restlessness. However, its potential role in managing behavioral and psychological symptoms of dementia (BPSD) in Alzheimer's disease (AD) is unclear.ObjectiveThis study evaluated the efficacy and safety of WCW as an adjunctive treatment for BPSD in patients with mild probable AD already receiving donepezil.MethodsSeventy-four patients receiving donepezil 5&#x2005;mg daily were randomized 1:1 into an intervention group (WCW add-on, n&#x2009;=&#x2009;37) or a control group (no additional treatment, n&#x2009;=&#x2009;37) for 24 weeks. The primary outcome was the change in BPSD measured using the Neuropsychiatric Inventory (NPI). Secondary outcomes were cognitive function and emotional and physical well-being, including depression, anxiety, insomnia, quality of life, and severity of dementia. Safety was assessed via adverse events and laboratory results.ResultsSixty-three participants were included. The WCW group demonstrated significantly improved total NPI scores versus controls, particularly in the irritability/lability subdomain. Analysis of covariance (ANCOVA) confirmed these findings in both the full analysis set (FAS) and per-protocol set (PPS). T-test and rank ANCOVA showed significance in the PPS and a trend in the FAS. The general quality of life dementia scale showed a trend toward improvement. No significant differences in adverse events or laboratory results were observed.ConclusionsWCW may be a safe and effective adjunctive therapy for BPSD in patients with mild probable AD. Future studies should adopt more rigorous designs and include patients with broader disease severity to enhance clinical applicability.Trial registrationThe trial was registered with the Clinical Research Information Service (CRIS) on December 10, 2020 (KCT0005669).

Facial palsy is a debilitating condition that can lead to significant functional, aesthetic, and psychosocial impairments. Thus, this study aimed to systematically explore treatment preferences and values among Korean patients with facial palsy and develop clinically applicable recommendations to enhance patient-centered care. A cross-sectional questionnaire survey was conducted between June and July 2025 at a facial palsy clinic in a secondary referral hospital. A total of 51 patients with peripheral facial palsy completed a structured 21-item survey addressing preferences related to assessment and diagnosis, treatment modalities, multidisciplinary care, communication, information sources, and recovery concerns. The internal consistency of the questionnaire was evaluated using Cronbach's alpha (&#x3b1;). Participants (mean age 43.1 &#xb1; 12.4 years; 68.6% female) prioritized objective assessment methods and accurate prognostic information, favoring standardized tools and electrophysiological testing. Regarding treatment preferences, 82.4% supported active steroid therapy and 74.5% preferred combined steroid-antiviral treatment. Surgery was generally viewed as a last resort, with 51.0% favoring non-surgical rehabilitation even in chronic cases-those persisting for more than six months. Multidisciplinary care and clear, detailed communication were highly valued. The primary recovery concern was permanent facial sequelae (64.7%). Meanwhile, the internal consistency of the survey, which covered diverse and independent domains, was rather poor (Cronbach's &#x3b1; = 0.548), reflecting the multidimensional nature of the patient preferences. Korean patients with facial palsy express a strong fear of permanent sequelae, which shapes the preferences of patients toward objective information and treatments with high efficacy. Moreover, the patients were found to favor comprehensive multidisciplinary care, clear and transparent communication, and collaborative relationships with healthcare providers. These findings provide important insights for developing patient-centered clinical guidelines tailored to Korean patients with facial palsy.