Annals of Clinical and Translational Neurology最新文献

{"title":"Fixel-Based Analysis of Diffusion Imaging as a Quantitative Marker of Disease State in Spinocerebellar Ataxia.","authors":"David J Arpin, S H Subramony, David E Vaillancourt, Tetsuo Ashizawa, Alexandra Durr, Thomas Mareci, Thomas Klockgether, Jennifer Faber, Henry L Paulson, Gülin Öz, Matthew R Burns","doi":"10.1002/acn3.70116","DOIUrl":"https://doi.org/10.1002/acn3.70116","url":null,"abstract":"<p><strong>Objective: </strong>Spinocerebellar ataxias (SCAs) are a group of genetically heterogeneous neurodegenerative diseases causing progressive deterioration and reduced quality of life. Therapeutic advances have been limited by a lack of sensitive anatomic, functional, or diffusion imaging-based biomarkers. This study aimed to identify white matter differences in the brains of preataxic and early-stage SCA1 and SCA3 mutation carriers using diffusion magnetic resonance imaging data from a multisite trial setting.</p><p><strong>Methods: </strong>Fixel-based analysis was used to estimate microscopic fiber density, macroscopic fiber-bundle cross-section, and a combined fiber density and fiber-bundle cross-section measure within 45 cerebral and cerebellar tracts. Multivariate ANOVAs compared controls (n = 16), pre-ataxic (n = 10 SCA1, n = 24 SCA3), and ataxic patients (n = 14 SCA1, n = 36 SCA3). Clinical variables were correlated with fixel metrics and receiver operating characteristic analyses identified white matter tracts sensitive to distinguishing controls from pre-ataxic SCA1 and SCA3.</p><p><strong>Results: </strong>We found widespread white matter deficits in pre-ataxic and ataxic patients compared to controls with regard to fiber density, fiber-bundle cross-section, and combined measures, all of which were associated with clinical measures of ataxia severity. We also found the combined fiber density and fiber-bundle cross-section measure from cerebellar tracts distinguished controls from pre-ataxia with high sensitivity and specificity for both SCA1 (receiver operating characteristic area under the curve = 0.96) and SCA3 (area under the curve = 0.97). The receiver operating characteristic analyses revealed that cerebellar tracts resulted in greater area under the curve than cortico-spinal and transcallosal tracts.</p><p><strong>Interpretation: </strong>These results demonstrate that fixel metrics offer sensitive disease-specific measures of early SCA disease state that correlate with standard clinical measures.</p><p><strong>Trial registration: </strong>Clinical Trial Readiness for SCA1 and SCA3 (READISCA), NCT03487367. https://clinicaltrials.gov/ct2/show/NCT03487367.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144641317","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cognitive Resilience in Apolipoprotein ε4 Carrier Women Predicted by Neuron-Derived Extracellular Vesicles.","authors":"Apostolos Manolopoulos, Maja Mustapic, Carlos Nogueras-Ortiz, Francheska Delgado-Peraza, Krishna A Pucha, Pamela J Yao, Joseph Blommer, Michael P Vreones, William York, De' Larrian Knight, Stephen R Rapp, Aladdin H Shadyab, JoAnn E Manson, Ramon Casanova, Robert B Wallace, Luigi Ferrucci, Susan M Resnick, Dimitrios Kapogiannis","doi":"10.1002/acn3.70143","DOIUrl":"https://doi.org/10.1002/acn3.70143","url":null,"abstract":"<p><strong>Objective: </strong>The Apolipoprotein (APOE) ε4 allele is the strongest genetic risk factor for late-onset Alzheimer's disease (AD); however, many ε4 carriers remain cognitively intact into old age. Leveraging plasma neuron-derived extracellular vesicles (NDEVs), we sought to identify biomarkers of cognitive resilience and their interplay with APOE genotype.</p><p><strong>Methods: </strong>In this case-control study nested within the Women's Health Initiative (WHI), we analyzed 1130 plasma samples from 676 women in the WHI Memory Study (WHIMS)/Long Life Study (LLS), with APOE ε4 or ε3/ε3 genotypes. At baseline, all participants were cognitively intact and at LLS visit, 13-17 years later, were classified as still cognitively intact (resilient) or having become impaired at age > 80 or ≤ 80 years. We isolated NDEVs using immunoaffinity capture for the neuronal marker L1CAM and quantified AD pathogenic proteins (Aβ₄₂, total Tau, p181-Tau), insulin signaling (pSer312-IRS-1), TNFR1/NFκB pathway mediators and targets, and mitochondrial Complex V. Linear mixed models assessed group differences, adjusting for NDEV yield, age, and education, with FDR correction.</p><p><strong>Results: </strong>No group differences were found for Aβ₄₂, Tau proteins, or pS312-IRS-1. Resilient ε4 carriers had higher baseline levels of phosphorylated TNFR1, NFκB, c-Myc, and FADD than ε4 carriers who eventually developed impairment at > 80 or ≤ 80 years. Additionally, resilient ε4 carriers had higher baseline Complex V levels than ε4 carriers impaired at age > 80.</p><p><strong>Interpretation: </strong>Augmented neuronal TNFR1/NFκB signaling and Complex V levels may promote cognitive resilience in ε4 carrier women. Boosting these mechanisms may have preventive and therapeutic potential against cognitive decline in this high-risk population.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144641315","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative Effect of Standard Versus Extended Interval Dosing of Rituximab or Ocrelizumab in Multiple Sclerosis.","authors":"Nabil K El Ayoubi, Fares Fahd, Hani Tamim, Salem Hannoun, Mark Bal, Elham El-Hallak, Samia J Khoury","doi":"10.1002/acn3.70142","DOIUrl":"https://doi.org/10.1002/acn3.70142","url":null,"abstract":"<p><strong>Objective: </strong>We aimed to investigate the comparative effectiveness of standard versus personalized extended interval dosing of anti-CD20 therapy on clinical and sub-clinical outcomes in multiple sclerosis.</p><p><strong>Methods: </strong>Clinical information was collected prospectively on Research Electronic Data Capture. Patients with age ≥ 18 years old, confirmed diagnosis of multiple sclerosis, treatment with B-cell depleting drug (Rituximab and Ocrelizumab), and minimum follow-up of 12 months with at least 3 clinical visits and at least 3 infusions of medication were included and divided into an extended interval dosing group, a standard interval dosing group, and a converters group who switched from standard to extended interval dosing. Retinal measures were obtained using spectral domain Optical Coherence Tomography. Magnetic resonance imaging acquisitions were performed in two centers using a standardized conventional imaging protocol for multiple sclerosis.</p><p><strong>Results: </strong>Patients had a median clinical follow-up of 3.5 (0.44-7.3) years, retinal OCT follow-up of 2.6 (1.4) years, and MRI follow-up of 2.6 (1.1) years. Annualized changes in clinical measures, retinal measures, and brain volumetric measures were similar between the 3 groups. Multivariate regression analyses also showed no differences.</p><p><strong>Interpretation: </strong>We found no differences in clinical or sub-clinical outcomes between patients treated with standard interval dosing, patients converting from standard to extended interval dosing, and patients on extended interval dosing of B-cell depleting drugs.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144641316","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Associations of Stroke With Risk of Epilepsy: Results From the Atherosclerosis Risk in Communities (ARIC) Study.","authors":"Jiping Zhou, Asma A Ladak, Connor A Law, Michelle C Johansen, Anny Reyes, Silvia Koton, Sean Kelly, Jeubin Huang, Kamakshi Lakshminarayan, Rebecca F Gottesman, Emily Johnson, Andrea L C Schneider","doi":"10.1002/acn3.70144","DOIUrl":"https://doi.org/10.1002/acn3.70144","url":null,"abstract":"<p><strong>Objective: </strong>To estimate the risk of epilepsy associated with stroke in a community-based cohort, with consideration of stroke type, number, and severity.</p><p><strong>Methods: </strong>Data from 15,100 Atherosclerosis Risk in Communities (ARIC) Study participants without stroke at baseline (1987-1989) were analyzed through 12/31/2022. Adjudicated stroke events were modeled as time-varying exposures. Epilepsy was defined using International Classification of Diseases Ninth/Tenth Revisions codes. Adjusted Fine and Gray proportional hazards models were used to estimate the risk of epilepsy associated with stroke.</p><p><strong>Results: </strong>At baseline, the mean age of participants was 54 years, 55% were female, and 26% were of Black race. Over a median of 27 years, 1553 incident all-cause strokes occurred. The risk of epilepsy was higher among individuals with versus without incident stroke (HR = 1.75, 95% CI = 1.50-2.04). There was evidence for interaction by age (p-interaction = 0.03) whereby the risk of epilepsy associated with stroke was higher among individuals with younger versus older baseline age. Compared to no stroke, the point estimate for the risk of epilepsy associated with subarachnoid hemorrhage (HR = 2.94, 95% CI = 1.67-5.17) was higher than that for the risk of epilepsy associated with ischemic stroke (HR = 1.65, 95% CI = 1.40-1.94) and hemorrhagic stroke (HR = 1.47, 95% CI = 0.95, 2.27). The risk of epilepsy was similar by the number of incident strokes but was greater with increasing ischemic stroke severity.</p><p><strong>Interpretation: </strong>The risk of epilepsy was increased after an incident stroke. This work identifies high-risk subgroups, including younger individuals, individuals with subarachnoid hemorrhage, and individuals with more severe ischemic strokes, who may benefit from closer clinical monitoring for seizures/epilepsy after a stroke.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144641314","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Discovery and Treatment of Action Potential-Independent Myotonia in Hyperkalemic Periodic Paralysis.","authors":"Chris Dupont, Adam Deardorff, Murad Nawaz, Andrew A Voss, Mark M Rich","doi":"10.1002/acn3.70134","DOIUrl":"https://doi.org/10.1002/acn3.70134","url":null,"abstract":"<p><strong>Objective: </strong>Hyperkalemic periodic paralysis (hyperKPP) is characterized by attacks of transient weakness. A subset of hyperKPP patients suffers from transient involuntary contraction of muscle (myotonia). The goal of this study was to determine mechanisms causing myotonia in hyperKPP.</p><p><strong>Methods: </strong>Intracellular electrophysiology, single-fiber Ca²⁺ imaging, and whole muscle contractility studies were performed in a mouse model of hyperKPP.</p><p><strong>Results: </strong>Myotonia in hyperkPP was caused by both involuntary myogenic action potentials (AP myotonia) lasting less than 5 min and action potential-independent myotonia (non-AP myotonia) lasting over 1 h. Non-AP myotonia was caused by prolonged subthreshold depolarization and elevated intracellular Ca²⁺ in the absence of action potentials. Treatment with dantrolene effectively mitigated non-AP myotonia, suggesting that the source of Ca²⁺ was the sarcoplasmic reticulum. Although non-AP myotonia occurred in the absence of action potentials, Na⁺ channel blockers were effective as therapy.</p><p><strong>Discussion: </strong>We propose myotonia in hyperKPP occurs via two mechanisms: (1) suprathreshold depolarization triggering action potentials that are detectable with EMG and (2) sustained subthreshold depolarization resulting in Na⁺ overload and Ca²⁺ leak from the sarcoplasmic reticulum. Notably, clinical diagnostics such as EMG cannot detect the second mechanism as it occurs in the absence of action potentials. Currently, only a minority of patients with hyperKPP are treated with Na⁺ channel blockers and none are treated with dantrolene. Our data suggest hyperKPP patients, as well as patients with a number of other neuromuscular disorders, may benefit from trials of these therapies, even if they do not have myotonia detectable clinically or by EMG.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144625091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The MSA Atrophy Index (MSA-AI): An Imaging Marker for Diagnosis and Clinical Progression in Multiple System Atrophy.","authors":"Paula Trujillo, Kilian Hett, Amy Cooper, Amy E Brown, Jessica Iregui, Manus J Donahue, M Erik Landman, Italo Biaggioni, Margaret Bradbury, Cynthia Wong, David Stamler, Daniel O Claassen","doi":"10.1002/acn3.70106","DOIUrl":"https://doi.org/10.1002/acn3.70106","url":null,"abstract":"<p><strong>Objective: </strong>Reliable biomarkers are essential for tracking disease progression and advancing treatments for multiple system atrophy (MSA). In this study, we propose the MSA Atrophy Index (MSA-AI), a novel composite volumetric measure to distinguish MSA from related disorders and monitor disease progression.</p><p><strong>Methods: </strong>Seventeen participants with an initial diagnosis of probable MSA were enrolled in the longitudinal bioMUSE study and underwent 3T MRI, biofluid analysis, and clinical assessments at baseline, 6, and 12 months. Final diagnoses were determined after 12 months using clinical progression, imaging, and fluid biomarkers. Ten participants retained an MSA diagnosis, while five were reclassified as either Parkinson disease (PD, n = 4) or dementia with Lewy bodies (DLB, n = 1). Cross-sectional comparisons included additional MSA cases (n = 26), healthy controls (n = 23), pure autonomic failure (n = 23), PD (n = 56), and DLB (n = 8). Lentiform nucleus, cerebellum, and brainstem volumes were extracted using deep learning-based segmentation. Z-scores were computed using a normative dataset (n = 469) and integrated into the MSA-AI. Group differences were tested with linear regression; longitudinal changes and clinical correlations were assessed using mixed-effects models and Spearman correlations.</p><p><strong>Results: </strong>MSA patients exhibited significantly lower MSA-AI scores compared to all other diagnostic groups (p < 0.001). The MSA-AI effectively distinguished MSA from related synucleinopathies, correlated with baseline clinical severity (ρ = -0.57, p < 0.001), and predicted disease progression (ρ = -0.55, p = 0.03). Longitudinal reductions in MSA-AI were associated with worsening clinical scores over 12 months (ρ = -0.61, p = 0.01).</p><p><strong>Interpretation: </strong>The MSA-AI is a promising imaging biomarker for diagnosis and monitoring disease progression in MSA. These findings require validation in larger, independent cohorts.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144635790","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"BCS1L-Associated Disease: 5'-UTR Variant Shifts the Phenotype Towards Axonal Neuropathy.","authors":"Rotem Orbach, Nunziata Maio, Russell J Butterfield, A Reghan Foley, Sarah Silverstein, Yan Li, Katherine Chao, Tanya J Lehky, Abigail Potticary, Tracey A Rouault, Sandra Donkervoort, Carsten G Bönnemann","doi":"10.1002/acn3.70108","DOIUrl":"https://doi.org/10.1002/acn3.70108","url":null,"abstract":"<p><strong>Objectives: </strong>To investigate the consequences of a pathogenic missense variant (c.838C>T; p.L280F) and a 5'-UTR regulatory variant (c.-122G>T) in BCS1L on disease pathogenesis and to understand how regulatory variants influence disease severity and clinical presentation.</p><p><strong>Methods: </strong>Deep phenotyping, research-based whole genome sequencing, biochemical characterization of identified variants, and studies in patient-derived fibroblast cultures were applied to uncover the underlying genetic cause and molecular defects in siblings with a genetically uncharacterized complex neurologic condition.</p><p><strong>Results: </strong>Genome sequencing identified a paternally inherited missense variant (c.838C>T; p.L280F) and a maternally inherited 5'-UTR variant (c.-122G>T) in BCS1L in two affected siblings. Although the missense variant disrupts complex III assembly, the 5'-UTR variant allows residual wild-type BCS1L expression, likely mitigating disease severity. Biochemical studies in patient-derived fibroblasts confirmed the pathogenicity of both variants and demonstrated a moderate in vitro response to a coenzyme Q10 analog.</p><p><strong>Interpretation: </strong>This study expands the clinical spectrum of BCS1L-related disorders to include a comparatively milder phenotype with central and peripheral nervous system involvement. Our findings demonstrate that the 5'-UTR variant modulates disease severity by enabling residual wild-type BCS1L expression, partially mitigating the pathogenic effects of the missense variant. These insights underscore the importance of evaluating both protein coding and regulatory variants in mitochondrial disease diagnostics and pathogenesis.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144635789","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quantitative Shape Irregularity and Density Heterogeneity Predict Hematoma Expansion in Patients With Intracerebral Hemorrhage.","authors":"Zeqiang Ji, Yunyi Hao, Bin Gao, Xiaojing Zhang, Yani Zhang, Jiaokun Jia, Xue Xia, Yuhao Guo, Sijia Li, Jianwei Wu, Kaijiang Kang, Xingquan Zhao","doi":"10.1002/acn3.70141","DOIUrl":"https://doi.org/10.1002/acn3.70141","url":null,"abstract":"<p><strong>Purpose: </strong>This study aimed to explore the association between quantitative shape irregularity and density heterogeneity of hematomas and hematoma expansion (HE) for intracerebral hemorrhage (ICH) patients.</p><p><strong>Methods: </strong>This cohort study included patients arriving within 24 h of symptom onset between August 2021 and July 2022 as the derivation cohort and those between July 2023 and February 2024 as the external validation cohort. HE is defined as a hematoma increase of > 6 mL or > 33% from the baseline to the follow-up CT scan between 24 and 48 h. The least absolute shrinkage and selection operator (LASSO) regression was applied to select the traditional image signs to fit the logistic regression as Model 1. Afterwards, the surface regularity index (SRI) and density coefficient of variation (DCV) of hematoma were added to form Model 2. Finally, we used the SRI and DCV to replace the selected traditional image signs as Model 3. The performance and clinical utilities were evaluated and compared in the external validation cohort.</p><p><strong>Result: </strong>The three models demonstrated good discrimination in both the derivation cohort and the validation cohort, with Model 2 and Model 3 showing significant improvements in area under the receiver operating characteristic curve (AUROC) and in clinical utility compared to Model 1 (Model 2 AUROC: 0.859 [95% CI: 0.802, 0.926] vs. Model 1 AUROC: 0.713 [95% CI: 0.625, 0.814], Delong test p < 0.001; Model 3 AUROC: 0.840 [95% CI: 0.776, 0.912] vs. Model 1 AUROC: 0.713 [95% CI: 0.625, 0.814], p = 0.006). The SRI and DCV can improve the prediction of HE based on traditional clinical indicators and imaging signs, also serving as possible alternatives to traditional imaging signs.</p><p><strong>Conclusions: </strong>The SRI and DCV can serve as effective substitutes for traditional imaging signs in predicting hematoma expansion.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144625092","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glial Fibrillary Acidic Protein Astrocytopathy Based on a Two-Center Chinese Cohort Study.","authors":"Ti Wu, Hao Zhang, Chao Gao, Qiuhua Yu, Moli Fan, Lin-Jie Zhang, Haipeng Zhang, Hengri Cong, Yuzhen Wei, Chotima Böttcher, Alexej Verkhratsky, Friedemann Paul, Fu-Dong Shi, Tian Song","doi":"10.1002/acn3.70118","DOIUrl":"https://doi.org/10.1002/acn3.70118","url":null,"abstract":"<p><strong>Objective: </strong>Glial fibrillary acidic protein astrocytopathy (GFAP-A) is a recently defined nosological form belonging to the class of autoimmune inflammatory disorders affecting the central nervous system (CNS). Here, we report the clinical and MRI characteristics, treatment, and prognosis of a GFAP-A cohort from two centers in China.</p><p><strong>Methods: </strong>We retrospectively analyzed the data from 38 adult patients with positive GFAP antibodies and diagnosed as GFAP-A between June 2019 and September 2024. Clinical features, semiquantitative antibody test results, MRI features, treatment approaches, and prognosis were collected.</p><p><strong>Results: </strong>Among the 38 patients, 24 were male, and the median age at disease onset was 49.5 years. The clinical phenotype included encephalomyelitis (28.9%), myelitis (23.7%), encephalitis (18.4%), meningoencephalomyelitis (18.4%), meningitis/spinal meningitis (7.9%), and peripheral neuropathy (2.6%). In enhanced MRI images, 4 (10.5%) of the patients showed enhancement of the cerebral meninges, 2 (5.3%) had enhancement of the ependyma, and 5 (13.2%) had enhancement of the spinal cord pia mater. 77.1% of the patients responded to the glucocorticoid treatment, while 65.8% had a monophasic course. Spearman correlation analysis showed that CSF-specific oligoclonal bands were significantly correlated with 1-year relapse (CI = 0.527, p = 0.003).</p><p><strong>Interpretation: </strong>The clinical manifestations of GFAP-A are highly diverse, encompassing encephalitis, myelitis, and meningitis, including spinal meningitis. The enhancement of the spinal pia mater and ependyma on MRI was confirmed. Most patients exhibit a positive response to glucocorticoid therapy. The presence of CSF-specific oligoclonal bands could potentially serve as an indicator for predicting recurrence.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144606931","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Digital Activity Markers in Chronic Inflammatory Demyelinating Polyneuropathy.","authors":"Lars Masanneck, Jan Voth, Noëmi Gmahl, Konstantin Jendretzky, Niklas Huntemann, Noah M Werner, Linea Schmidt, Menekse Oeztuerk, Paula Quint, Christina B Schroeter, Hans Peter Hartung, Thomas Skripuletz, Gerd Meyer Zu Hörste, Tobias Ruck, Sven G Meuth, Marc Pawlitzki","doi":"10.1002/acn3.70137","DOIUrl":"https://doi.org/10.1002/acn3.70137","url":null,"abstract":"<p><strong>Objective: </strong>To evaluate the utility of smartwatch and smartphone-based activity metrics for assessing disease severity and quality of life in patients with chronic inflammatory demyelinating polyneuropathy (CIDP).</p><p><strong>Methods: </strong>In the electronic monitoring of disease activity in patients with CIDP (EMDA-CIDP) trial, we performed a prospective observational study from January 2023 to July 2024 at university hospitals in Düsseldorf and Münster, with an independent validation cohort in Hannover. Eligible participants were adults with CIDP on stable intravenous immunoglobulin (IVIG) therapy. Clinical evaluations included established disability scales (I-RODS and INCAT) and quality of life assessments. Activity metrics were captured via consumer-grade smartwatches, with adherence criteria applied to ensure data quality. A real-world smartphone-based cohort of 20 patients was used as a comparator.</p><p><strong>Results: </strong>Among 46 participants (median age 64 Years [IQR 57-69]; 24% female), smartwatch-derived maximum daily-step count emerged as a robust indicator of disease severity. In 43 patients meeting wearable adherence criteria, maximum daily steps showed strong correlations with clinical scores, positively with I-RODS (Spearman's ρ = 0.74) and inversely with INCAT (Spearman's ρ = -0.54). Additional smartwatch metrics correlated with quality of life domains, whereas smartphone-derived metrics of a validation cohort exhibited weaker correlations.</p><p><strong>Interpretation: </strong>These results indicate that smartwatches many patients already use can yield valuable, objective data for assessing disease status in CIDP. Integrating smartwatch-derived metrics into clinical assessments may enhance traditional evaluations and deepen understanding of disease progression and patient quality of life. These promising results warrant additional, larger-scale studies in the future.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144598976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}