Annals of Clinical and Translational Neurology最新文献

{"title":"Real-World Comparison of High-Efficacy Versus Non-High-Efficacy Therapies in Multiple Sclerosis","authors":"Sarmad Al-Araji,&nbsp;Marcello Moccia,&nbsp;Alessia Bianchi,&nbsp;Charmaine Yam,&nbsp;Weaam Hamed,&nbsp;Suraya Mohamud,&nbsp;Alan J. Thompson,&nbsp;Frederik Barkhof,&nbsp;Ahmed T. Toosy,&nbsp;Olga Ciccarelli","doi":"10.1002/acn3.70130","DOIUrl":"10.1002/acn3.70130","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>The choice of the first disease modifying treatment (DMT) in multiple sclerosis (MS) is a topic of great interest, and whether high-efficacy DMTs should be the first choice remains debated. We compared treatment outcomes (no evidence of disease activity [NEDA] and its components) between treatment-naïve relapsing–remitting MS (RRMS) patients commencing high-efficacy therapies (HET) and non-high-efficacy therapies (non-HET), using propensity score matching.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This is an observational prospective study of two real-world, single-centre, longitudinal cohorts: (1) Relapsing–remitting MS (RRMS) patients initiated dimethyl fumarate, fingolimod, glatiramer acetate and natalizumab between 2002 and 2020; (2) RRMS patients initiated ocrelizumab between 2019 and 2021. We selected treatment-naïve patients and had at least 2 years of follow-up. We compared the two groups at years 1 and 2 using Cox and Logistic regression models as appropriate.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>After propensity score matching, we included 448 patients: 110 HET and 338 non-HET. The probability of losing NEDA was 57% and 39% lower in the HET group at year 1 and 2 (HR = 0.43; 95% CI = 0.35, 0.52; <i>p</i> &lt; 0.01 and HR = 0.61; 95% CI = 0.45, 0.84; <i>p</i> &lt; 0.01, respectively). The probability of relapse in the HET group was 94% and 71% lower at year 1 and 2 (OR = 0.06; 95% CI = 0.01, 0.28; <i>p</i> &lt; 0.01 and OR = 0.29; 95% CI = 0.10, 0.84; <i>p</i> &lt; 0.02, respectively). The EDSS in the HET group was 30% and 18% lower at year 1 and 2 (Coeff = −0.30; 95% CI = −0.42, −0.18; <i>p</i> &lt; 0.01 and Coeff = −0.16; 95% CI = −0.34, 0.02; <i>p</i> &lt; 0.09, respectively). The probability of MRI activity in the HET group was 82% lower at year 1 (OR = 0.18; 95% CI = 0.04, 0.86; <i>p</i> &lt; 0.03).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>This study demonstrated that treatment-naïve RRMS patients should be considered for high-efficacy therapies based on a greater suppression of disease activity at 2 years.</p>\u0000 </section>\u0000 </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"12 10","pages":"2077-2085"},"PeriodicalIF":3.9,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/acn3.70130","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144648068","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fixel-Based Analysis of Diffusion Imaging as a Quantitative Marker of Disease State in Spinocerebellar Ataxia","authors":"David J. Arpin,&nbsp;S. H. Subramony,&nbsp;the READISCA Consortium,&nbsp;David E. Vaillancourt,&nbsp;Tetsuo Ashizawa,&nbsp;Alexandra Durr,&nbsp;Thomas Mareci,&nbsp;Thomas Klockgether,&nbsp;Jennifer Faber,&nbsp;Henry L. Paulson,&nbsp;Gülin Öz,&nbsp;Matthew R. Burns","doi":"10.1002/acn3.70116","DOIUrl":"10.1002/acn3.70116","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>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>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>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 (<i>n</i> = 16), pre-ataxic (<i>n</i> = 10 SCA1, <i>n</i> = 24 SCA3), and ataxic patients (<i>n</i> = 14 SCA1, <i>n</i> = 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>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>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>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>These results demonstrate that fixel metrics offer sensitive disease-specific measures of early SCA disease state that correlate with standard clinical measures.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Trial Registration</h3>\u0000 \u0000 <p>Clinical Trial Readiness for SCA1 and SCA3 (READISCA), NCT03487367. https://clinicaltrials.gov/ct2/show/NCT03487367.</p>\u0000 </section>\u0000 </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"12 9","pages":"1846-1857"},"PeriodicalIF":3.9,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/acn3.70116","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NMDAR-Antibody Encephalitis Diagnosed With Primary Central Nervous System Lymphoma: A Case Series","authors":"Soo Hyun Ahn,&nbsp;Cynthea Prima,&nbsp;Tae Min Kim,&nbsp;Soon-Tae Lee,&nbsp;Kon Chu","doi":"10.1002/acn3.70090","DOIUrl":"10.1002/acn3.70090","url":null,"abstract":"<p><i>N</i>-methyl-D-aspartate receptor-antibody encephalitis (NMDAR encephalitis) is one of the most common forms of autoimmune encephalitis, with a paraneoplastic relationship described in approximately 38%. Primary central nervous system lymphoma (PCNSL) is a rare hematologic malignancy that is not often considered as the underlying neoplasm in this autoimmune disease. We report three cases of suspected NMDAR encephalitis diagnosed in the context of PCNSL. Our cases highlight clinical features to suspect the coexistence of these two rare conditions and demonstrate the potential role PCNSL can play as the paraneoplastic source condition.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"12 9","pages":"1913-1918"},"PeriodicalIF":3.9,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/acn3.70090","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144937138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","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,&nbsp;Fares Fahd,&nbsp;Hani Tamim,&nbsp;Salem Hannoun,&nbsp;Mark Bal,&nbsp;Elham El-Hallak,&nbsp;Samia J. Khoury","doi":"10.1002/acn3.70142","DOIUrl":"10.1002/acn3.70142","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>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>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>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>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>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>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>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>\u0000 </section>\u0000 </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"12 10","pages":"2086-2096"},"PeriodicalIF":3.9,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/acn3.70142","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":"OA","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,&nbsp;Kilian Hett,&nbsp;Amy Cooper,&nbsp;Amy E. Brown,&nbsp;Jessica Iregui,&nbsp;Manus J. Donahue,&nbsp;M. Erik Landman,&nbsp;Italo Biaggioni,&nbsp;Margaret Bradbury,&nbsp;Cynthia Wong,&nbsp;David Stamler,&nbsp;Daniel O. Claassen","doi":"10.1002/acn3.70106","DOIUrl":"10.1002/acn3.70106","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>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>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>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, <i>n</i> = 4) or dementia with Lewy bodies (DLB, <i>n</i> = 1). Cross-sectional comparisons included additional MSA cases (<i>n</i> = 26), healthy controls (<i>n</i> = 23), pure autonomic failure (<i>n</i> = 23), PD (<i>n</i> = 56), and DLB (<i>n</i> = 8). Lentiform nucleus, cerebellum, and brainstem volumes were extracted using deep learning-based segmentation. Z-scores were computed using a normative dataset (<i>n</i> = 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>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>MSA patients exhibited significantly lower MSA-AI scores compared to all other diagnostic groups (<i>p</i> &lt; 0.001). The MSA-AI effectively distinguished MSA from related synucleinopathies, correlated with baseline clinical severity (<i>ρ</i> = −0.57, <i>p</i> &lt; 0.001), and predicted disease progression (<i>ρ</i> = −0.55, <i>p</i> = 0.03). Longitudinal reductions in MSA-AI were associated with worsening clinical scores over 12 months (<i>ρ</i> = −0.61, <i>p</i> = 0.01).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>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>\u0000 </section>\u0000 </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"12 9","pages":"1823-1833"},"PeriodicalIF":3.9,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/acn3.70106","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":"OA","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,&nbsp;Yunyi Hao,&nbsp;Bin Gao,&nbsp;Xiaojing Zhang,&nbsp;Yani Zhang,&nbsp;Jiaokun Jia,&nbsp;Xue Xia,&nbsp;Yuhao Guo,&nbsp;Sijia Li,&nbsp;Jianwei Wu,&nbsp;Kaijiang Kang,&nbsp;Xingquan Zhao","doi":"10.1002/acn3.70141","DOIUrl":"10.1002/acn3.70141","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Purpose</h3>\u0000 \u0000 <p>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>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>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 &gt; 6 mL or &gt; 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>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Result</h3>\u0000 \u0000 <p>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 <i>p</i> &lt; 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], <i>p</i> = 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>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The SRI and DCV can serve as effective substitutes for traditional imaging signs in predicting hematoma expansion.</p>\u0000 </section>\u0000 </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"12 10","pages":"2068-2076"},"PeriodicalIF":3.9,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/acn3.70141","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":"OA","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,&nbsp;Hao Zhang,&nbsp;Chao Gao,&nbsp;Qiuhua Yu,&nbsp;Moli Fan,&nbsp;Lin-Jie Zhang,&nbsp;Haipeng Zhang,&nbsp;Hengri Cong,&nbsp;Yuzhen Wei,&nbsp;Chotima Böttcher,&nbsp;Alexej Verkhratsky,&nbsp;Friedemann Paul,&nbsp;Fu-Dong Shi,&nbsp;Tian Song","doi":"10.1002/acn3.70118","DOIUrl":"10.1002/acn3.70118","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>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>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>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>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>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, <i>p</i> = 0.003).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>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>\u0000 </section>\u0000 </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"12 9","pages":"1813-1822"},"PeriodicalIF":3.9,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/acn3.70118","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Digital Activity Markers in Chronic Inflammatory Demyelinating Polyneuropathy","authors":"Lars Masanneck,&nbsp;Jan Voth,&nbsp;Noëmi Gmahl,&nbsp;Konstantin Jendretzky,&nbsp;Niklas Huntemann,&nbsp;Noah M. Werner,&nbsp;Linea Schmidt,&nbsp;Menekse Oeztuerk,&nbsp;Paula Quint,&nbsp;Christina B. Schroeter,&nbsp;Hans Peter Hartung,&nbsp;Thomas Skripuletz,&nbsp;Gerd Meyer zu Hörste,&nbsp;Tobias Ruck,&nbsp;Sven G. Meuth,&nbsp;Marc Pawlitzki","doi":"10.1002/acn3.70137","DOIUrl":"10.1002/acn3.70137","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>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>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>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>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>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 <i>ρ</i> = 0.74) and inversely with INCAT (Spearman's <i>ρ</i> = −0.54). Additional smartwatch metrics correlated with quality of life domains, whereas smartphone-derived metrics of a validation cohort exhibited weaker correlations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>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>\u0000 </section>\u0000 </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"12 10","pages":"2045-2055"},"PeriodicalIF":3.9,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/acn3.70137","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Validated Model to Predict Severe Weight Loss in Amyotrophic Lateral Sclerosis","authors":"David G. Lester,&nbsp;Kevin Talbot,&nbsp;Martin R. Turner,&nbsp;Alexander G. Thompson,&nbsp;the Pooled Resource Open-Access ALS Clinical Trials Consortium","doi":"10.1002/acn3.70129","DOIUrl":"10.1002/acn3.70129","url":null,"abstract":"<p>Severe weight loss in amyotrophic lateral sclerosis (ALS) is common, multifactorial, and associated with shortened survival. Using longitudinal weight data from over 6000 patients with ALS across three cohorts, we built an accelerated failure time model to predict the risk of future severe (≥ 10%) weight loss using five single-timepoint clinical predictors: symptom duration, revised ALS Functional Rating Scale, site of onset, forced vital capacity, and age. Model performance and generalisability were evaluated using internal–external cross-validation and random-effects meta-analysis. The overall concordance statistic was 0.71 (95% CI 0.63–0.79), and the calibration slope and intercept were 0.91 (0.69–1.13) and 0.05 (−0.11–0.21). This study highlights clinical factors most associated with severe weight loss in ALS and provides the basis for a stratification tool.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"12 9","pages":"1907-1912"},"PeriodicalIF":3.9,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/acn3.70129","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144937150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In Vitro Modeling of Natural Killer Cell Cytotoxicity to Inform Personalized ALS Therapeutics","authors":"Benjamin J. Murdock,&nbsp;Jihyun Park,&nbsp;Dae-Gyu Jang,&nbsp;Bangyao Zhao,&nbsp;Samuel J. Teener,&nbsp;Ian F. Webber-Davis,&nbsp;Lili Zhao,&nbsp;Eva L. Feldman,&nbsp;Stephen A. Goutman","doi":"10.1002/acn3.70127","DOIUrl":"10.1002/acn3.70127","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Natural killer (NK) cells might contribute to motor neuron death in amyotrophic lateral sclerosis (ALS) through direct cytotoxicity, a process that could be inhibited with the FDA-approved JAK/STAT pathway inhibitor, tofacitinib. This study aimed to verify that tofacitinib can suppress NK cell cytotoxicity, investigate if immune cell profiles can predict responsiveness to tofacitinib, and assess the role of NK cell cytotoxicity in ALS progression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Primary NK cells were isolated from peripheral blood samples of ALS participants and healthy controls. NK cells were then co-cultured with target cancer cells, with or without tofacitinib, to assess their cytotoxic activity. Flow cytometry was used to generate immune profiles for each participant, based on 154 immune markers, to explore correlations with NK cell cytotoxicity and response to tofacitinib. The potential association between NK cell cytotoxicity and disease severity, as measured by the revised ALS Functional Rating Scale, was also assessed. All analyses were stratified by age and sex.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Tofacitinib effectively reduced the cytotoxicity of primary NK cells isolated from the blood of ALS participants (<i>n</i> = 80) and healthy controls (<i>n</i> = 71), with immune cell profiles correlating with the response to tofacitinib. However, NK cell cytotoxicity was lower in ALS participants compared to healthy controls and showed no association with ALS progression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>These findings confirm that tofacitinib suppresses NK cell cytotoxicity, and that immune profiling may help identify treatment responder groups. However, further research is needed to fully understand the role and timing of NK cell activity in ALS pathogenesis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"12 10","pages":"2036-2044"},"PeriodicalIF":3.9,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/acn3.70127","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144590095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}