Annals of Clinical and Translational Neurology最新文献

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The Case of a 25-Year-Old Woman With Isolated Head Tremor. 一例25岁女性孤立性头部震颤。
IF 3.9 2区 医学
Annals of Clinical and Translational Neurology Pub Date : 2025-10-09 DOI: 10.1002/acn3.70221
Ying Zhao, Zhihong Xu, Xingyu Zhuang, Yuying Zhao, Chuanzhu Yan, Kunqian Ji
{"title":"The Case of a 25-Year-Old Woman With Isolated Head Tremor.","authors":"Ying Zhao, Zhihong Xu, Xingyu Zhuang, Yuying Zhao, Chuanzhu Yan, Kunqian Ji","doi":"10.1002/acn3.70221","DOIUrl":"https://doi.org/10.1002/acn3.70221","url":null,"abstract":"<p><p>This study reported a 25-year-old woman with isolated head tremors as the main manifestation, along with type 1 diabetes, bilateral hearing loss, and leukoencephalopathy, who was diagnosed with mitochondrial disease due to a single large mtDNA deletion (m.8647-16082del).</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145256946","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}
引用次数: 0
Clinical Characteristics and Outcomes of Early-Onset Versus Late-Onset LGI1-Antibody Encephalitis. 早发性lgi1抗体脑炎与晚发性lgi1抗体脑炎的临床特点和结局。
IF 3.9 2区 医学
Annals of Clinical and Translational Neurology Pub Date : 2025-10-08 DOI: 10.1002/acn3.70223
Yu Kong, Shasha Yu, Jing Zhang, Yu Zu, Yujing Zhang, Jing Lv, Xuyang Cao, Xuedan Feng
{"title":"Clinical Characteristics and Outcomes of Early-Onset Versus Late-Onset LGI1-Antibody Encephalitis.","authors":"Yu Kong, Shasha Yu, Jing Zhang, Yu Zu, Yujing Zhang, Jing Lv, Xuyang Cao, Xuedan Feng","doi":"10.1002/acn3.70223","DOIUrl":"https://doi.org/10.1002/acn3.70223","url":null,"abstract":"<p><strong>Background: </strong>Leucine-rich glioma-inactivated 1 antibody (LGI1-Ab) encephalitis predominantly affected older individuals, but has also been reported in younger patients. However, the demographic, clinical, and prognostic characteristics of early-onset LGI1-Ab encephalitis have yet to be systematically elucidated. This study aims to systematically describe the clinical features and outcomes of early-onset LGI1-Ab encephalitis and compare them with those of later-onset cases.</p><p><strong>Methods: </strong>A total of 105 patients with LGI1-Ab encephalitis admitted to the Department of Neurology at Beijing Fengtai You'anmen Hospital were enrolled in this study between January 2019 and December 2024. All patients were divided into early-onset (age at onset younger than 50 years) and late-onset (age at onset 50 years or older) groups. Demographic, clinical, paraclinical, and prognostic data were compared between the two groups.</p><p><strong>Results: </strong>Among the cohort, 30 (28.5%) patients had early-onset LGI1-Ab encephalitis, with a female predominance (17, 56.7%). Epileptic seizures, psychiatric and behavioral symptoms, and memory impairment were the most common symptoms both at disease onset and throughout the disease course. Compared to later-onset patients, early-onset patients exhibited a lower prevalence of faciobrachial dystonic seizures (FBDS) (p = 0.041) and hyponatremia (p = 0.003). Additionally, they had higher serum albumin (p = 0.012), lower CSF protein (p = 0.006), lower age-normalized QAlb (p = 0.001), and fewer epileptic waves (p = 0.041). As for prognosis, memory deficits (11/30, 36.7%) were the most common residual symptom at follow-up, and early-onset patients were less likely to relapse (p = 0.038).</p><p><strong>Conclusions: </strong>This study provides the first systematic characterization of early-onset LGI1-Ab encephalitis. Compared to late-onset cases, early-onset patients showed a lower incidence of hyponatremia, milder blood-brain barrier disruption, and fewer clinical relapses.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145243277","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}
引用次数: 0
Diffusion Tractography Biomarker for Epilepsy Severity in Children With Drug-Resistant Epilepsy. 弥散束造影对耐药癫痫患儿癫痫严重程度的生物标志物。
IF 3.9 2区 医学
Annals of Clinical and Translational Neurology Pub Date : 2025-10-08 DOI: 10.1002/acn3.70217
Jeong-Won Jeong, Min-Hee Lee, Hiroshi Uda, Yoon Ho Hwang, Michael Behen, Aimee Luat, Csaba Juhász, Eishi Asano
{"title":"Diffusion Tractography Biomarker for Epilepsy Severity in Children With Drug-Resistant Epilepsy.","authors":"Jeong-Won Jeong, Min-Hee Lee, Hiroshi Uda, Yoon Ho Hwang, Michael Behen, Aimee Luat, Csaba Juhász, Eishi Asano","doi":"10.1002/acn3.70217","DOIUrl":"https://doi.org/10.1002/acn3.70217","url":null,"abstract":"<p><strong>Objective: </strong>To develop a novel deep-learning model of clinical DWI tractography that can accurately predict the general assessment of epilepsy severity (GASE) in pediatric drug-resistant epilepsy (DRE) and test if it can screen diverse neurocognitive impairments identified through neuropsychological assessments.</p><p><strong>Methods: </strong>DRE children and age-sex-matched healthy controls were enrolled to construct an epilepsy severity network (ESN), whose edges were significantly correlated with GASE scores of DRE children. An ESN-based biomarker called the predicted GASE score was obtained using dilated deep convolutional neural network with a relational network (dilated DCNN+RN) and used to quantify the risk of neurocognitive impairments using global/verbal/non-verbal neuropsychological assessments of 36/37/32 children performed on average 3.2 ± 2.7 months prior to the MRI scan. To warrant the generalizability, the proposed biomarker was trained and evaluated using separate development and independent test sets, with the random score learning experiment included to assess potential overfitting.</p><p><strong>Results: </strong>The dilated DCNN+RN outperformed other state-of-the art methods to create the predicted GASE scores with significant correlation (r = 0.92 and 0.83 for development and test sets with clinical GASE scores) and minimal overfitting (r = -0.25 and 0.00 for development and test sets with random GASE scores). Both univariate and multivariate models demonstrated that compared with the clinical GASE scores, the predicted GASE scores provide better model fit and discriminatory ability, suggesting more adjusted and accurate estimate of epilepsy severity contributing to the overall risk.</p><p><strong>Interpretation: </strong>The proposed biomarker shows strong potential for early identification of DRE children at risk of neurocognitive impairments, enabling timely, personalized interventions to prevent long-term effects.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145249057","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}
引用次数: 0
CSF Levels of NPTX2 Are Associated With Less Brain Atrophy Over Time in Cognitively Unimpaired Individuals. 随着时间的推移,在认知功能未受损的个体中,脑脊液NPTX2水平与较少的脑萎缩有关。
IF 3.9 2区 医学
Annals of Clinical and Translational Neurology Pub Date : 2025-10-08 DOI: 10.1002/acn3.70216
Juan P Vazquez, Corinne Pettigrew, Yuxin Zhu, Claire Anderson, Guray Erus, Christos Davatzikos, Michael Miller, Abhay Moghekar, Sungtaek Oh, Chan-Hyun Na, Marilyn Albert, Paul Worley, Anja Soldan
{"title":"CSF Levels of NPTX2 Are Associated With Less Brain Atrophy Over Time in Cognitively Unimpaired Individuals.","authors":"Juan P Vazquez, Corinne Pettigrew, Yuxin Zhu, Claire Anderson, Guray Erus, Christos Davatzikos, Michael Miller, Abhay Moghekar, Sungtaek Oh, Chan-Hyun Na, Marilyn Albert, Paul Worley, Anja Soldan","doi":"10.1002/acn3.70216","DOIUrl":"https://doi.org/10.1002/acn3.70216","url":null,"abstract":"<p><strong>Introduction: </strong>Neuronal pentraxin 2 (NPTX2) is a synaptic protein involved in synaptic plasticity and regulation of neuronal excitability. Lower baseline cerebrospinal fluid (CSF) NPTX2 levels have been shown to be associated with an earlier onset of mild cognitive impairment (MCI), a pre-dementia syndrome, even after CSF Alzheimer's Disease (AD) biomarkers (amyloid beta (Aβ<sub>42/40</sub>), and phosphorylated tau (p-tau<sub>181</sub>)) were considered. To date, however, it is not known whether CSF NPTX2 levels among cognitively unimpaired individuals are associated with longitudinal brain atrophy.</p><p><strong>Objective(s): </strong>Evaluate the association between baseline CSF NPTX2 levels and measures of long-term brain atrophy in participants who were cognitively unimpaired at baseline.</p><p><strong>Methods: </strong>Analyses included 213 participants (M baseline age = 57.2 years, 62% female) from the prospective longitudinal BIOCARD study with 13.9 years (max = 22.6 years) of magnetic resonance imaging (MRI) follow-up, on average. CSF NPTX2 was measured as a composite of three correlated peptides obtained by quantitative parallel reaction monitoring mass spectrometry. MRI brain atrophy was measured longitudinally with three composites. This included two spatial patterns of atrophy: (1) a composite of AD-signature regions (SPARE-AD) and (2) a composite of regions sensitive to brain aging (SPARE-BA), with higher values indicating more atrophy. Additionally, (3) a medial temporal lobe (MTL) composite included volumes of the amygdala, hippocampus, and entorhinal cortex. Linear mixed effect models assessed the association of baseline NPTX2 levels with the rate of change in the brain atrophy measures.</p><p><strong>Results: </strong>When covarying biomarkers of AD pathology (i.e., the ratio of CSF p-tau<sub>181</sub>/(Aβ<sub>1-42</sub>/Aβ<sub>1-40</sub>), age, sex, APOE4 genetic status, and years of education), lower baseline NPTX2 levels were associated with greater atrophy over time in both AD-vulnerable regions (SPARE-AD, standardized estimate = -0.008, p = 0.034) as well as regions sensitive to brain aging (SPARE-BA, standardized estimate = -0.011, p = 0.014). These associations were independent of participants having follow-up diagnoses of MCI or dementia.</p><p><strong>Conclusion: </strong>Our findings suggest that after accounting for biomarkers of AD pathology, CSF NPTX2 is associated with slower longitudinal atrophy in AD-signature and aging-related regions. These findings are consistent with the view that NPTX2 may be a resilience factor in the presence of pathology and modifies rates of neurodegeneration.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145249040","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}
引用次数: 0
Interleukin-6 as a Key Biomarker in Facioscapulohumeral Dystrophy: Evidence From Longitudinal Analyses. 白介素-6作为面肩肱骨营养不良的关键生物标志物:来自纵向分析的证据。
IF 3.9 2区 医学
Annals of Clinical and Translational Neurology Pub Date : 2025-10-07 DOI: 10.1002/acn3.70210
Jonathan Pini, Emanuela Martinuzzi, Sandra Dhifallah, Abderhmane Slioui, Angela Puma, Luisa Villa, Michele Cavalli, Andra Ezaru, Jérémy Garcia, Manuela Gambella, Federico Torre, Luca Jacopo Pavan, Nicolas Glaichenhaus, Sabrina Sacconi
{"title":"Interleukin-6 as a Key Biomarker in Facioscapulohumeral Dystrophy: Evidence From Longitudinal Analyses.","authors":"Jonathan Pini, Emanuela Martinuzzi, Sandra Dhifallah, Abderhmane Slioui, Angela Puma, Luisa Villa, Michele Cavalli, Andra Ezaru, Jérémy Garcia, Manuela Gambella, Federico Torre, Luca Jacopo Pavan, Nicolas Glaichenhaus, Sabrina Sacconi","doi":"10.1002/acn3.70210","DOIUrl":"https://doi.org/10.1002/acn3.70210","url":null,"abstract":"<p><strong>Objective: </strong>Facioscapulohumeral muscular dystrophy type 1 (FSHD1) is a progressive neuromuscular disorder with no approved treatments. Identifying reliable biomarkers is critical to monitor disease severity, activity, and progression. Interleukin-6 (IL-6) has been proposed as a candidate biomarker, but longitudinal validation is limited.</p><p><strong>Methods: </strong>We analyzed pooled data from two prospective longitudinal cohorts: CTRN-FSHD France (NCT04038138) and Cytokine FSHD (NCT04694456), each comprising 30 genetically confirmed ambulant FSHD1 patients. Serum IL-6 levels and clinical assessments were collected at baseline (M0), 12 months (M12), and 18 months (M18); whole-body muscle MRI (T1-weighted and STIR sequences) was obtained at M0 and M12. Associations between IL-6 levels and clinical severity scores, functional measures, and MRI-derived muscle composition were evaluated.</p><p><strong>Results: </strong>Serum IL-6 levels correlated significantly with clinical severity metrics, including Clinical Severity Score, 6-Minute Walk Test, Manual Muscle Testing, and Motor Function Measure Domain 1 at all time points. Higher IL-6 levels were associated with increased muscle fat infiltration and free water content compatible with muscle edema on MRI. Longitudinal analyses showed that increases in IL-6 over 12 months were significantly correlated with changes in T1 (fat infiltration) and STIR (muscle edema) composite scores, reflecting structural and inflammatory disease progression.</p><p><strong>Interpretation: </strong>These findings validate IL-6 as a biomarker of FSHD1 severity and underscore its potential as an activity and progression biomarker. The correlation between IL-6, clinical scores, and MRI-based muscle composition changes highlights its potential utility for monitoring disease evolution and evaluating therapeutic responses in FSHD1 patients.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145243261","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}
引用次数: 0
Systemic T Cell Receptor Profiling Reveals Adaptive Immune Activation and Potential Immune Signatures of Diagnosis and Brain Atrophy in Epilepsy. 系统性T细胞受体谱分析揭示癫痫诊断和脑萎缩的适应性免疫激活和潜在免疫特征。
IF 3.9 2区 医学
Annals of Clinical and Translational Neurology Pub Date : 2025-10-07 DOI: 10.1002/acn3.70203
Yong-Won Shin, Sang Bin Hong, Yong Woo Shin, Inpyeong Hwang, Jaeseong Oh, Jihyeon Choi, Narae Kim, Jangsup Moon, Keun-Hwa Jung, Kyung-Il Park, Ki-Young Jung, Kon Chu, Sang Kun Lee
{"title":"Systemic T Cell Receptor Profiling Reveals Adaptive Immune Activation and Potential Immune Signatures of Diagnosis and Brain Atrophy in Epilepsy.","authors":"Yong-Won Shin, Sang Bin Hong, Yong Woo Shin, Inpyeong Hwang, Jaeseong Oh, Jihyeon Choi, Narae Kim, Jangsup Moon, Keun-Hwa Jung, Kyung-Il Park, Ki-Young Jung, Kon Chu, Sang Kun Lee","doi":"10.1002/acn3.70203","DOIUrl":"https://doi.org/10.1002/acn3.70203","url":null,"abstract":"<p><strong>Objective: </strong>Epilepsy is increasingly associated with immune dysregulation and inflammation. The T cell receptor (TCR), a key mediator of adaptive immunity, shows repertoire alterations in various immune-mediated diseases. The unique TCR sequence serves as a molecular barcode for T cells, and clonal expansion accompanied by reduced overall TCR repertoire diversity reflects adaptive immune activation. We investigated peripheral TCR repertoire changes in epilepsy and their association with disease severity and brain atrophy.</p><p><strong>Methods: </strong>We profiled TCR α/β chain repertoires from peripheral blood mononuclear cells of 100 individuals, including 45 patients with epilepsy (14 with well-controlled epilepsy, 22 with drug-resistant epilepsy [DRE], and 9 with neuroinflammation-associated epilepsy [NIE]) and 55 unmatched healthy controls. NIE included new-onset epilepsy following possible autoimmune or infectious neuroinflammation. We comprehensively evaluated clonotype distribution, diversity, interindividual sharing, and V/J gene usage. Machine learning models evaluated the diagnostic potential of TCR repertoire features. Brain volumes were measured by MRI and correlated with TCR repertoire characteristics.</p><p><strong>Results: </strong>Patients with epilepsy showed significantly reduced TCR diversity, particularly in DRE or NIE. They also showed distinct patterns of V and J gene usage and decreased interindividual sharing of epilepsy-associated clonotypes. Machine learning models incorporating V/J usage and public clonotypes distinguished patients with epilepsy from controls with a mean classification accuracy of 0.80 (95% bias-corrected and accelerated bootstrap confidence interval (BCa CI), 0.69-0.86) and the area under the curve of 0.80 (95% BCa CI, 0.70-0.87). TCR diversity correlated with seizure frequency among patients without daily seizures or clinical evidence of neuroinflammation. Brain atrophy, notably in the thalamus and basal ganglia, was also associated with TCR repertoire alterations and specific V/J gene usage patterns.</p><p><strong>Interpretation: </strong>Peripheral TCR repertoire profiling reveals that systemic immune dysregulation is present in epilepsy and is associated with neurodegeneration. Our findings highlight the peripheral TCR repertoire as a disease-relevant immune signature with the potential to non-invasively interrogate epilepsy status and guide therapeutic interventions.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145243292","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}
引用次数: 0
Reply to: Commentary on "The Impact of Diabetes and Metabolic Syndrome Burden on Pain, Neuropathy Severity and Fiber Type". 回复:关于“糖尿病和代谢综合征负担对疼痛、神经病变严重程度和纤维类型的影响”的评论
IF 3.9 2区 医学
Annals of Clinical and Translational Neurology Pub Date : 2025-10-07 DOI: 10.1002/acn3.70150
Long Davalos, Brian C Callaghan, Amro M Stino
{"title":"Reply to: Commentary on \"The Impact of Diabetes and Metabolic Syndrome Burden on Pain, Neuropathy Severity and Fiber Type\".","authors":"Long Davalos, Brian C Callaghan, Amro M Stino","doi":"10.1002/acn3.70150","DOIUrl":"https://doi.org/10.1002/acn3.70150","url":null,"abstract":"","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145237586","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}
引用次数: 0
SNUPN-Related Muscular Dystrophy: Novel Phenotypic, Pathological and Functional Protein Insights. snupn相关的肌营养不良:新的表型,病理和功能蛋白的见解。
IF 3.9 2区 医学
Annals of Clinical and Translational Neurology Pub Date : 2025-10-06 DOI: 10.1002/acn3.70211
Nuria Muelas, Pablo Iruzubieta, Alberto Damborenea, Laura Pérez-Fernández, Inmaculada Azorín, Juan Carlos Jiménez García, Ana Töpf, Pilar Martí, Lorena Fores-Toribio, María Manterola, Rosana Blanco-Mañez, Oihane Pikatza-Menoio, Sonia Alonso-Martín, Volker Straub, Aitziber L Cortajarena, Adolfo López de Munain, David De Sancho, Lorea Blázquez, Juan J Vilchez
{"title":"SNUPN-Related Muscular Dystrophy: Novel Phenotypic, Pathological and Functional Protein Insights.","authors":"Nuria Muelas, Pablo Iruzubieta, Alberto Damborenea, Laura Pérez-Fernández, Inmaculada Azorín, Juan Carlos Jiménez García, Ana Töpf, Pilar Martí, Lorena Fores-Toribio, María Manterola, Rosana Blanco-Mañez, Oihane Pikatza-Menoio, Sonia Alonso-Martín, Volker Straub, Aitziber L Cortajarena, Adolfo López de Munain, David De Sancho, Lorea Blázquez, Juan J Vilchez","doi":"10.1002/acn3.70211","DOIUrl":"https://doi.org/10.1002/acn3.70211","url":null,"abstract":"<p><strong>Objective: </strong>SNUPN-related muscular dystrophy or LGMDR29 is a new entity that covers from a congenital or childhood onset pure muscular dystrophy to more complex phenotypes combining neurodevelopmental features, cataracts, or spinocerebellar ataxia. So far, 12 different variants have been described. Here we report the first family with SNUPN-related muscular dystrophy presenting an adult-onset myopathy as well as novel ultrastructural findings.</p><p><strong>Methods: </strong>Clinical evaluation, muscle and brain magnetic resonance imaging (MRI), and muscle histopathological and electron microscopy analysis were conducted. Functional studies including protein modelling and interaction, immunofluorescence and splicing analysis were also performed.</p><p><strong>Results: </strong>Two siblings carrying two novel deleterious variants in the SNUPN gene (p.Arg27Cys and p.Cys174Tyr) showed adult-onset proximo-distal and axial muscle weakness with early respiratory involvement. One patient presented with asymptomatic cerebellar atrophy. Muscle MRI identified involvement in the paravertebral, triceps brachii, sartorius and gracilis muscles. The histopathology revealed dystrophic changes and an abnormal pattern of cytoskeletal and myofibrillar proteins, while electron microscopy disclosed the proliferation of granules and vesicles associated with features of nuclear envelope and sarcolemma remodelling. Functional studies showed that SNUPN variants impair snurportin-1 function through reduced binding affinity to importin-β and impaired folding, leading to disturbed nuclear import of small nuclear ribonucleoproteins and downstream splicing.</p><p><strong>Interpretation: </strong>Our work expands the phenotype of SNUPN-related muscular dystrophy and provides more insights into their pathological profile. We advise SNUPN testing in patients with late-onset proximo-distal and axial weakness with early respiratory impairment and features reminding inclusion body myositis (IBM). Granular deposits suggestive of biomolecular condensates perturbed cell organelle traffic and membrane homeostasis, opening new avenues to understand the pathomechanisms involved in this novel disease.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145237562","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}
引用次数: 0
Relapsing-Remitting Multiple Sclerosis Is Associated With a Dysbiotic Oral Microbiome. 复发缓解型多发性硬化症与口腔微生物群失调有关
IF 3.9 2区 医学
Annals of Clinical and Translational Neurology Pub Date : 2025-10-06 DOI: 10.1002/acn3.70212
Sukirth M Ganesan, Meeta Yadav, Sudeep Ghimire, Peter C Lehman, Apurva J Patel, Sydney Woods, Heena Olalde, Jemmie Hoang, Mishelle Paullus, Catherine Cherwin, Christine Gill, Tracey Cho, Ashutosh K Mangalam
{"title":"Relapsing-Remitting Multiple Sclerosis Is Associated With a Dysbiotic Oral Microbiome.","authors":"Sukirth M Ganesan, Meeta Yadav, Sudeep Ghimire, Peter C Lehman, Apurva J Patel, Sydney Woods, Heena Olalde, Jemmie Hoang, Mishelle Paullus, Catherine Cherwin, Christine Gill, Tracey Cho, Ashutosh K Mangalam","doi":"10.1002/acn3.70212","DOIUrl":"https://doi.org/10.1002/acn3.70212","url":null,"abstract":"<p><strong>Objective: </strong>Multiple sclerosis (MS) is a chronic autoimmune disorder characterized by inflammation, demyelination, and neurological impairment. While the gut microbiota's role in MS is extensively studied, the association between the oral microbiota and MS remains underexplored, particularly in North American cohorts. This study aimed to investigate the microbiota (bacterial) composition as well as functional pathways and immune profiles of the oral cavity in 60 patients with relapsing-remitting MS (RRMS), stratified by treatment status, compared to 44 healthy controls (HC).</p><p><strong>Methods: </strong>Unstimulated saliva was collected for genomic DNA extraction and salivary cytokine quantification. Oral bacterial composition and diversity were analyzed using 16S rRNA sequencing, with functional pathways inferred using PICRUSt2. Salivary cytokine levels were measured via multiplex immunoassays. LEfSe and random forest models identified key discriminatory taxa, and correlations between microbiota and cytokines were assessed using Spearman's rank analysis.</p><p><strong>Results: </strong>RRMS patients exhibited distinct microbial communities compared to HC and a higher Bacteroidota to Firmicutes ratio. Key taxa such as Campylobacter, Lachnoanaerobaculum, and Porphyromonas were enriched in RRMS. Functional profiling revealed 49 differentially abundant pathways, including the enrichment of lipopolysaccharide biosynthesis in MS. Elevated levels of IFN-γ, IL-6, and other cytokines correlated with the altered microbiome. IL-21, elevated in HC, correlated with anti-inflammatory pathways, suggesting a protective role in immune homeostasis.</p><p><strong>Interpretation: </strong>This study provides, for the first time, insights into oral microbiome-host interactions in North American RRMS patients, underscoring the interplay between microbial dysbiosis, functional pathways, and immune dysregulation. The oral microbiome shows potential as a biomarker for MS-related immune alterations.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145231183","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}
引用次数: 0
NR4A1 Exerts Pro-Tumor Role in Glioblastoma via Inducing xCT/GPX4-Regulated Ferroptosis. NR4A1通过诱导xCT/ gpx4调控的铁凋亡在胶质母细胞瘤中发挥促瘤作用。
IF 3.9 2区 医学
Annals of Clinical and Translational Neurology Pub Date : 2025-10-06 DOI: 10.1002/acn3.70173
Peng Tao, Shikuan Din, Zhengkang Fu, Qian Sun, Xiwei Zhu, Yuxin Wei, Huan Qu, Xinyi Zhang, Jiaxuan Liu, Chuhua Fu, Qianxue Chen
{"title":"NR4A1 Exerts Pro-Tumor Role in Glioblastoma via Inducing xCT/GPX4-Regulated Ferroptosis.","authors":"Peng Tao, Shikuan Din, Zhengkang Fu, Qian Sun, Xiwei Zhu, Yuxin Wei, Huan Qu, Xinyi Zhang, Jiaxuan Liu, Chuhua Fu, Qianxue Chen","doi":"10.1002/acn3.70173","DOIUrl":"https://doi.org/10.1002/acn3.70173","url":null,"abstract":"<p><strong>Purpose: </strong>This study investigates NR4A1's paradoxical roles in glioblastoma (GBM) progression, focusing on its mechanistic link to ferroptosis regulation. We aimed to resolve conflicting reports of NR4A1 as both an oncogene and a tumor suppressor by defining its transcriptional control over xCT/GPX4-mediated iron homeostasis and its clinical relevance in glioma survival.</p><p><strong>Methods: </strong>TCGA cohort analysis (n = 163) correlated NR4A1 expression with survival endpoints (OS/PFI/DSS, log-rank p < 0.05). Functional validation employed U87/U251 GBM models for viability (CCK-8), proliferation (EdU/colony formation), and migration assays (Transwell/wound healing). RNA sequencing (DESeq2, FDR < 0.05) and ChIP-qPCR identified NR4A1-xCT transcriptional regulation. Ferroptosis was quantified via lipid peroxidation (MDA/GSH/Fe<sup>2+</sup> ELISA, C11 BODIPY), while Western blotting mapped the NR4A1/xCT/GPX4/P53 axis. Orthotopic xenografts (n = 6/group) evaluated therapeutic efficacy using biweekly tumor volumetry. All data were analyzed in triplicate (GraphPad Prism 8.0; t-test/ANOVA, *p < 0.05).</p><p><strong>Conclusion: </strong>NR4A1 drives GBM progression by transcriptionally activating xCT/GPX4 to suppress ferroptosis. Dual targeting of NR4A1 and ferroptosis pathways synergistically inhibits tumor growth (64% reduction vs. controls, p = 0.008), providing a mechanistic rationale for overcoming therapy resistance in GBM.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145237603","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}
引用次数: 0
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