BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) can occur in the elderly, but the efficacy and safety of conventional immunosuppressive therapies (ISTs) in this population remain unclear. METHODS: We conducted...BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) can occur in the elderly, but the efficacy and safety of conventional immunosuppressive therapies (ISTs) in this population remain unclear. METHODS: We conducted a retrospective target-trial emulation using the Korean National Health Insurance Service database from 2011 to 2022. We constructed 636 weekly emulated trials and included 1020 patients who initiated ISTs and 1965 untreated patients after propensity score matching. The primary outcome was relapse incidence and safety outcomes included serious infection and other adverse events. Age-stratified analyses were prespecified using 60 years as the cutoff. RESULTS: IST recipients had a lower annual relapse incidence than untreated patients, although the adjusted hazard ratio (aHR) did not reach statistical significance (aHR 0.57, 95% CI 0.28-1.19). Age-stratified analyses suggested a numerical relapse reduction in patients aged <60 years, but not in those aged ≥60 years, although statistical significance was not reached. Over the follow-up period, the overall risk of serious infection was similar between groups (aHR 1.11, 95% CI 0.84-1.46). Within the first 6 months after IST initiation, the risk of serious infection was increased, particularly among patients aged ≥60 years (aHR 5.80, 95% CI 2.05-16.40). CONCLUSIONS: Evidence was insufficient to determine whether the efficacy of ISTs is reduced in elderly patients with NMOSD. However, IST use was associated with an increased early risk of serious infection, especially among patients aged ≥60 years, suggesting that treatment decisions in older patients require more careful consideration.
BACKGROUND: The underlying mechanism of neuropsychiatric features of Long COVID remains unclear; however, the most compelling hypothesis is the contribution of excessive neuroinflammation induced by a systemic inflammato...BACKGROUND: The underlying mechanism of neuropsychiatric features of Long COVID remains unclear; however, the most compelling hypothesis is the contribution of excessive neuroinflammation induced by a systemic inflammatory response or cytokine storm. We aimed to investigate the neuropsychiatric features of Long COVID in older adults and the potential association with neuroinflammation measured by [F]FEPPA positron emission tomography (PET) targeting translocator protein (TSPO). METHODS: A total of 24 individuals aged 60 or older participated in the study: those with Long COVID symptoms and persistent subjective or objective cognitive impairments for more than six months (n = 12) and age-matched healthy adults without Long COVID (n = 12). After assessments with neuropsychiatric scales and cognitive testing batteries, three Long COVID and three healthy control participants, who were high-affinity binders to TSPO, underwent additional brain [F]FEPPA PET scans. RESULTS: Long COVID group (n = 12) showed significantly higher levels of depression and fatigue compared to the healthy control group (n = 12). With [F]FEPPA PET, the Long COVID group (n = 3) showed significantly higher binding levels in all compared brain regions, such as the prefrontal, temporal, parietal, and occipital neocortices, and the hippocampus, thalamus, and cerebellum, compared to the healthy control group (n = 3). CONCLUSION: Older adults with Long COVID showed greater neuropsychiatric symptoms, such as depression and fatigue, compared to healthy older adults. The [F]FEPPA PET findings suggest that their persistent neuropsychiatric symptoms could potentially be associated with chronic neuroinflammation.
BACKGROUND: Diffusion-weighted imaging (DWI) infarct volume and infarct growth are important imaging biomarkers in patients with acute ischemic stroke and treated with mechanical thrombectomy (MT), but manual measurement...BACKGROUND: Diffusion-weighted imaging (DWI) infarct volume and infarct growth are important imaging biomarkers in patients with acute ischemic stroke and treated with mechanical thrombectomy (MT), but manual measurement is time-consuming and resource-intensive. Deep learning (DL)-based automated segmentation may facilitate rapid and reliable assessment; however, its performance on hyperacute DWI and its prognostic value have not been fully validated. METHODS: We retrospectively analyzed consecutive patients with acute ischemic stroke treated with MT between September 2014 and December 2019 who underwent DWI on admission and at approximately 24 h. Infarct volumes were measured manually by stroke neurologists and automatically using a DL-based software. Agreement was assessed using Pearson's correlation, Bland-Altman analysis, and concordance correlation coefficient (CCC). Predictive abilities for good functional outcome at 3 months were compared between manual and automated measurements using C-statistics. RESULTS: A total of 371 patients (677 DWI scans) were included. Manual and automated infarct volumes showed very strong correlation (r = 0.94 for admission DWIs and 0.97 for follow-up DWIs) with minimal bias (-2.82 mL for admission and - 0.50 mL for follow-up). The CCC for manual-automated agreement was 0.935 for admission and 0.971 for follow-up, comparable to human inter- and intra-rater reliabilities. Agreement remained high across onset-to-imaging times. Predictive abilities for good outcome were similar between manual and automated admission DWI volume (C-statistics 0.867 vs. 0.861) and infarct growth (0.859 vs. 0.853). CONCLUSIONS: DL-based automated infarct volume measurement demonstrates substantial agreement with manual assessment and comparable prognostic performance, supporting its feasibility and reliability in hyperacute stroke management.
BACKGROUND: White matter hyperintensities (WMH) are common in idiopathic normal pressure hydrocephalus (iNPH), particularly in periventricular regions around the anterior horns. However, their quantitative evaluation usi...BACKGROUND: White matter hyperintensities (WMH) are common in idiopathic normal pressure hydrocephalus (iNPH), particularly in periventricular regions around the anterior horns. However, their quantitative evaluation using simple and reproducible methods and their association with cerebrospinal fluid (CSF) tap test responsiveness remain insufficiently studied. We investigated whether the extent of periventricular WMH around the anterior horn area is associated with responsiveness to the CSF tap test. METHODS: We retrospectively reviewed patients who underwent a CSF tap test and preprocedural MRI between January 2020 and September 2023. Periventricular WMH around the anterior horn area was manually quantified on axial T2-weighted fluid-attenuated inversion recovery images using freehand regions of interest. Gait and cognitive function were assessed using the 3-m Timed Up and Go test (3-TUG) and the Frontal Assessment Battery (FAB). Correlation, multivariable regression, and receiver operating characteristic (ROC) analyses were performed. RESULTS: Thirty-six patients were included. Inter-rater reliability for WMH measurements was good (intraclass correlation coefficient = 0.73). Larger WMH areas were associated with lower baseline FAB scores and longer disease duration. Although correlations with changes in 3-TUG or FAB scores were not significant, greater WMH burden was associated with smaller improvement after the CSF tap test. Multivariable analysis showed that WMH area independently predicted FAB score improvement. ROC analysis identified a WMH cutoff value of 254 mm for predicting ≥ 3-point FAB improvement (area under the curve = 0.728). CONCLUSIONS: Quantitative assessment of periventricular WMH around the anterior horn area may help predict cognitive responsiveness to the CSF tap test iNPH.
Duchenne muscular dystrophy (DMD) is a severe genetic disorder characterized by progressive muscle degeneration. This retrospective register and chart review study utilized data from Finnish registers and Helsinki Univer...Duchenne muscular dystrophy (DMD) is a severe genetic disorder characterized by progressive muscle degeneration. This retrospective register and chart review study utilized data from Finnish registers and Helsinki University Hospital to assess the epidemiology, treatment practices, and economic burden of DMD in Finland. Analysis of primary outcomes (incidence, prevalence, and mortality) included all males with a DMD diagnosis from 1996 to 2022 (N = 250). Secondary outcomes were studied in the cohort from 2013 to 2022. From 1996 to 2022, mean annual incidence of DMD was 0.98/5000 male newborns, and mean annual prevalence was 2.46/100,000 residents. Mean age at diagnosis was 6.5 years and median survival was 18.5 years after diagnosis. The most common causes of death were muscular dystrophy, pneumonia, and dilated cardiomyopathy. Secondary analyses of 175 patients found mean age at diagnosis was 5.8 years. Common comorbidities included respiratory failure (42.9%), scoliosis (39.4%), and pneumonia (38.3%). Annually, patients had a mean 7.0 primary and 11.0 secondary care contacts related to DMD; all-cause secondary care contacts contributed to 86.0% of patient healthcare costs. Diagnosis of DMD now occurs earlier compared with the beginning of the study period, and burden of disease and healthcare costs remain high and start at an early age.
BACKGROUND: Cerebral amyloid angiopathy (CAA) is a frequent cause of lobar intracerebral hemorrhage (ICH). While the Boston criteria version 2.0 enable in vivo CAA diagnosis using MRI features, the simplified Edinburgh C...BACKGROUND: Cerebral amyloid angiopathy (CAA) is a frequent cause of lobar intracerebral hemorrhage (ICH). While the Boston criteria version 2.0 enable in vivo CAA diagnosis using MRI features, the simplified Edinburgh CT criteria were proposed to overcome the limited access to MRI. We aimed to assess the agreement between them in a population-based setting. METHODS: Patients ≥50 years with lobar ICH were retrieved from the population-based Dijon Stroke Registry, France. Agreement between Edinburgh and Boston criteria was assessed using Cohen's kappa (κ), and a multinomial logistic regression was performed to investigate factors associated with discrepancies. Additionally, characteristics and outcomes were compared between included and excluded patients from the agreement analysis to investigate potential selection bias. RESULTS: Among 164 patients with lobar ICH, 71 had both brain CT and MRI available. Agreement between CT- and MRI-based criteria was poor (observed: 43.7%; κ = 0.16; SD: 0.075; 95% CI: 0.01-0.31). Patients with lack of agreement (n = 40) were older (median: 80.2 versus 73.7 years; p = 0.04), but the difference was no longer significant in multivariable model. Patients not included in the analysis (n = 93, mainly because of lack of MRI: n = 81) were older, had greater clinical, larger ICH volume, higher handicap at discharge, and lower 30-day survival than included patients. CONCLUSION: Agreement between CT and MRI criteria for CAA diagnosis in lobar ICH was poor, which raises questions about the reliability of CT alone for classifying CAA in ICH patients in our population-based registry.
INTRO: The heterogeneity of Essential Tremor (ET) complicates how it is diagnosed and studied. ET is often misdiagnosed as other neurological disorders and vice versa. We aimed to better understand ET by comparing brain...INTRO: The heterogeneity of Essential Tremor (ET) complicates how it is diagnosed and studied. ET is often misdiagnosed as other neurological disorders and vice versa. We aimed to better understand ET by comparing brain maps informed by ET common variants to those derived from related phenotypes. A further goal was to enhance the diagnostic precision of ET by accounting for shared genetic signals between ET and genetically overlapping phenotypes. METHODS: Phenotype variant association mapping to the brain was done for ET, Parkinson's disease (PD), dystonia, and cognition across adult mouse whole brain and cerebellum spatial transcriptomic data through gsMap. Separately, ET genome-wide association study (GWAS) summary statistics were conditioned on PD and cognition to account for shared genetic signals. Using both raw and conditioned GWASes, ET polygenic risk scores (PRS) were calculated across patient cohorts and controls, and their respective ability to classify ET at the 90th percentile was compared using McNemar's test. RESULTS: Spatial mappings of GWAS signals revealed many shared associations between phenotypes. The raw ET PRS model preformed 1.33% (95% CI: [0.30% - 2.35%]; p = 0.0129) better than the conditioned ET PRS model. CONCLUSION: We lack the ability to decern ET from related phenotypes using existing common variant disease associations. Efforts to isolate a core genetic signal for ET by de-noising shared associations reduced the accuracy of patient classification. Rare variants and lesser explored variant types may be key to unlocking informative variants for ET.
Schumacher FL, Cutter G, Burd CE
… +2 more, Archer K, Zhang Y
J Neurol Sci
· 2026 Jun · PMID 41924832
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Full text
Epigenetic clocks are composite measures of DNA methylation used as markers of biological age. This study found that epigenetic age acceleration (EAA) exhibits greater variability in individuals with multiple sclerosis (...Epigenetic clocks are composite measures of DNA methylation used as markers of biological age. This study found that epigenetic age acceleration (EAA) exhibits greater variability in individuals with multiple sclerosis (MS) compared to sex- and age-matched healthy controls (HC). Specifically, the standard deviation for PhenoAge in the secondary progressive (SP) MS group was 12.7, which is 1.5 times that of controls. A likelihood ratio test confirmed a significant difference in variance across relapsing remitting (RR) MS, SPMS, and HC groups, with a p-value of 0.017. This heterogeneity suggests future epigenetic aging studies in MS will require larger sample sizes and underscore the need for variance-aware sample size planning.