Annals of Clinical and Translational Neurology最新文献

{"title":"SGlycosylation Gene Signatures as Prognostic Biomarkers in Glioblastoma.","authors":"Tong Zhao, Hongliang Ge, Chenchao Lin, Xiyue Wu, Jianwu Chen","doi":"10.1002/acn3.70068","DOIUrl":"https://doi.org/10.1002/acn3.70068","url":null,"abstract":"<p><strong>Objective: </strong>Glioblastoma (GBM) is an aggressive brain tumor characterized by significant heterogeneity. This study investigates the role of glycosylation-related genes in GBM subtyping, prognosis, and response to therapy.</p><p><strong>Methods: </strong>We analyzed mRNA expression data and clinical information from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Glycosylation-related genes were selected for differential expression analysis, sample clustering, and survival analysis. Immune cell infiltration and drug sensitivity were evaluated using CIBERSORT and oncoPredict, respectively. A prognostic model was constructed with Lasso regression.</p><p><strong>Results: </strong>GBM samples were stratified into two glycosylation-related subtypes, showing distinct survival outcomes, with higher glycosylation expression correlating with poorer prognosis. Immune microenvironment analysis revealed differences in T-cell infiltration and immune checkpoint expression between subtypes, indicating variable immunotherapy responses. The prognostic model based on glycosylation genes demonstrated significant predictive value for patient survival.</p><p><strong>Conclusion: </strong>Glycosylation-related gene expression contributes to GBM heterogeneity and is a valuable biomarker for prognosis and treatment stratification. This study provides insights into personalized treatment approaches for GBM based on glycosylation-related molecular subtypes.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144092243","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 Impact of Diabetes and Metabolic Syndrome Burden on Pain, Neuropathy Severity and Fiber Type.","authors":"Long Davalos, Brian C Callaghan, Lavanya Muthukumar, Simone Thomas, Evan L Reynolds, A Gordon Smith, J Robinson Singleton, Ahmet Höke, Senda Ajroud-Driss, Mazen M Dimachkie, Stefanie Geisler, David M Simpson, Amro M Stino","doi":"10.1002/acn3.70072","DOIUrl":"https://doi.org/10.1002/acn3.70072","url":null,"abstract":"<p><strong>Objective: </strong>Determine the association between diabetes and metabolic syndrome (MetS) burden (number of MetS criteria fulfilled) and pain, neuropathy severity, and fiber type involvement in individuals with established polyneuropathy.</p><p><strong>Methods: </strong>The Peripheral Neuropathy Research Registry was queried for individuals with type 1 and type 2 diabetes (DPN) and non-diabetic peripheral neuropathy (cryptogenic sensory polyneuropathy and prediabetes) using cross-sectional observational data. Associations between diabetes or MetS burden and pain presence (yes/no), neuropathy severity (Total Neuropathy Score reduced), and fiber type involvement (pinprick, vibration, and proprioception examination-small, large, mixed) using logistic, linear, and multinomial regression models were determined.</p><p><strong>Results: </strong>A total of 1112 participants were included (265 DPN, 847 non-diabetic peripheral neuropathy [NDPN]). Compared to NDPN, DPN participants were more likely to have pain, higher neuropathy severity, and mixed fiber involvement. In adjusted models, diabetes was associated with pain (odds ratio [OR] 1.85, CI: 1.15-3.03) and severity (point estimate [PE] 0.84, CI: 0.27-1.42), but not fiber type involvement. As the MetS burden increased, pain, neuropathy severity, and mixed fiber type involvement increased (p < 0.05 for trend). In adjusted models, MetS burden was associated with pain (OR 1.23, CI: 1.06-1.41) but not severity or fiber type involvement.</p><p><strong>Interpretation: </strong>Participants with DPN were more likely to have pain, greater neuropathy severity, and possibly more mixed fiber involvement than those with NDPN. Similarly, increasing MetS burden also led to more painful neuropathy and possibly more severe neuropathy with more mixed fiber involvement.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144092244","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":"Military Service Roles and ALS Among Veterans: A Matched Case-Control Study.","authors":"Asaf Honig, Roy Dayan, Amir Knaani, Hagai Levine, Marc Gotkine","doi":"10.1002/acn3.70079","DOIUrl":"https://doi.org/10.1002/acn3.70079","url":null,"abstract":"<p><p>While military service is an established risk factor for amyotrophic lateral sclerosis (ALS), it remains unclear whether this association is linked to combat. We conducted a matched case-control study comparing 191 ALS patients who were veterans of the Israeli Defense Forces (IDF) with known military service type and 1910 matched controls. The ALS group had higher rates of combat service (46.0% vs. 22.7%) and parachuting (10.5% vs. 1.1%) in comparison with controls (p < 0.001 for both). In a multivariate model, combat service was associated with ALS (odds ratio 2.49, confidence interval [1.49-4.16], p < 0.01). The higher prevalence of combat roles among ALS patients expands our understanding of military service factors that contribute to ALS risk.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144092259","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":"Nuclei-Specific Amygdala Enlargement Is Linked to Psychiatric Comorbidities in Drug-Resistant Focal Epilepsy.","authors":"Hélène Mourre, Julia Makhalova, Lisa Soncin, Elodie Garnier, Hugo Dary, Arnaud Le Troter, Roy A M Haast, Benoit Testud, Marie Arthuis, Samuel Medina Villalon, Stanislas Lagarde, Francesca Pizzo, Christian Bénar, Jean-Philippe Ranjeva, Maxime Guye, Fabrice Bartolomei","doi":"10.1002/acn3.70071","DOIUrl":"https://doi.org/10.1002/acn3.70071","url":null,"abstract":"<p><strong>Objective: </strong>Amygdala enlargement has been the subject of controversial studies regarding its significance in terms of pathogenicity both in epilepsy and in psychiatric comorbidities such as anxiety, depression, and post-traumatic stress disorder. However, no causal link has been established in either direction, and the role of distinct amygdala nuclei remains unknown. We investigated volumetric changes of the amygdala and its nine main nuclei and their associations with psychiatric comorbidities in patients with drug-resistant focal epilepsy.</p><p><strong>Methods: </strong>Eighty-seven adult patients with drug-resistant focal epilepsy, available 7 T MRI, and completed standardized psychiatric assessments were included. Whole amygdala and nuclei volumes were quantified and compared to healthy controls. Correlations between the amygdala or nuclei volumes and psychiatric scores were analyzed, as well as the prevalence and severity of each comorbidity depending on the presence of enlargement.</p><p><strong>Results: </strong>Amygdala enlargement was present in 41% of patients, with bilateral enlargement observed in 30% of these cases, while atrophy was noted in 2%. Bilateral enlargement correlated with higher posttraumatic stress disorder and depression scores. Central nucleus enlargement was associated with a greater prevalence of depression and more severe anxiety. Bilateral enlargement of distinct nuclei in the basolateral group was linked to more severe depression or posttraumatic stress disorder.</p><p><strong>Interpretation: </strong>These findings suggest that bilateral amygdala enlargement, particularly in specific nuclei, may serve as a morphological marker of psychiatric comorbidities in epilepsy. Further research is needed to explore the specific roles of amygdala nuclei in psycho-epileptogenesis.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144092235","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":"Corrigendum to \"Clinical Phenotyping of Long COVID Patients Evaluated in a Specialized Neuro-COVID Clinic\".","authors":"","doi":"10.1002/acn3.70069","DOIUrl":"https://doi.org/10.1002/acn3.70069","url":null,"abstract":"","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144092256","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":"Patient Selection in Deep Brain Stimulation: A Role for Transcranial Direct Current Stimulation to Enhance the Levodopa Challenge?","authors":"Lukas L Goede, Patricia Zvarova, Bahne H Bahners, Andreas Horn","doi":"10.1002/acn3.70073","DOIUrl":"https://doi.org/10.1002/acn3.70073","url":null,"abstract":"<p><p>Dopaminergic medication and deep brain stimulation (DBS) improve motor symptoms in Parkinson's disease (PD), but levodopa response alone may not predict DBS outcomes. We retrospectively analyzed 19 PD patients undergoing levodopa challenges with and without prior transcranial direct current stimulation targeting a defined PD response network. Levodopa improved motor performance more after tDCS than sham (41.72% vs. 31.52%; p < 0.001). In ten patients who later received DBS, the combined levodopa-tDCS response accounted for DBS outcomes (p = 0.02). These findings suggest that targeted tDCS enhances levodopa effects and may be of potential use to optimize DBS candidate selection.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144092239","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":"Letter to: Real-World Clinical Experience With Serum MOG and AQP4 Antibody Testing by Live Versus Fixed Cell-Based Assay.","authors":"Adrian Budhram","doi":"10.1002/acn3.70062","DOIUrl":"https://doi.org/10.1002/acn3.70062","url":null,"abstract":"","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144074993","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":"HPDL Variant Type Correlates With Clinical Disease Onset and Severity.","authors":"Eun Hye Lee, Olivia Kim-Mcmanus, Jennifer H Yang, Richard Haas, Maha S Zaki, Ghada M H Abdel-Salam, Yuji Nakamura, Mohamed S Abdel-Hamind, Darius Ebrahimi-Fakhari, Julian E Alecu, Nicola Brunetti-Pierri, Varunvenkat M Srinivasan, Vykuntaraju K Gowda, Stephanie Gross, Yasemin Alanay, Paria Najarzadeh Totbati, Manya Yadavilli, Liana Friedman, Naomi Meave Ojeda, Joseph G Gleeson","doi":"10.1002/acn3.70047","DOIUrl":"https://doi.org/10.1002/acn3.70047","url":null,"abstract":"<p><strong>Objective: </strong>Recently, a mitochondrial encephalopathy due to biallelic HPDL variants was described, associated with a broad range of clinical manifestations ranging from severe, infantile-onset neurodegeneration to adolescence-onset hereditary spastic paraplegia. HPDL converts 4-hydroxyphenylpyruvate acid (4-HPPA) into 4-hydroxymandelate (4-HMA), necessary for the synthesis of the mitochondrial electron transporter CoQ10. This suggests a possible bypass of the metabolic block by 4-HMA treatment; however, genotype-phenotype correlations are lacking.</p><p><strong>Methods: </strong>We established an HPDL Patient Registry to prepare for a future clinical trial. Here we report the clinical features of 13 enrolled participants and compare them with 86 previously reported patients. We establish three major clinical classes: severe, intermediate, and mild, presenting onset in early infancy, childhood, and adolescence, respectively. The biallelic genotypes were classified into truncating/truncating, truncating/missense, and missense/missense variants, mapped onto the predicted 3D protein structure, and correlated with severity.</p><p><strong>Results: </strong>Patients with biallelic truncating variants presented with severe phenotypes and earlier ages of onset. Missense variants were often associated with milder phenotypes, except those with variants predominantly located in or near the VOC2 domain containing iron-binding sites or the C-terminus, which had more severe phenotypes. In addition, p.Met1? variants were also correlated with more severe phenotypes.</p><p><strong>Interpretation: </strong>This study demonstrates the correlation of age of onset and disease severity with genotype for HPDL-related conditions. Patients with truncating variants and specific missense variants correlated with severe, early-onset features, whereas the presence of at least one missense variant located outside of the iron-binding sites correlated with milder presentations.</p><p><strong>Trial registration: </strong>Clinicaltrials.gov HPDL registry: https://clinicaltrials.gov/study/NCT05848271.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144075009","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":"Myostatin Levels in SMA Following Disease-Modifying Treatments: A Multi-Center Study.","authors":"Fiorella Piemonte, Sara Petrillo, Anna Capasso, Giorgia Coratti, Adele D'Amico, Michela Catteruccia, Maria Carmela Pera, Concetta Palermo, Marika Pane, Emanuela Abiusi, Gianpaolo Cicala, Marianna Villa, Chiara Bravetti, Chiara Arpaia, Agnese Novelli, Salvatore Falqui, Stefania Fiori, Giulia Napoli, Silvia Baroni, Francesco Danilo Tiziano, Enrico Bertini, Giacomo Comi, Stefania Corti, Eugenio Mercuri","doi":"10.1002/acn3.70070","DOIUrl":"https://doi.org/10.1002/acn3.70070","url":null,"abstract":"<p><strong>Objective: </strong>This study investigated myostatin levels in SMA patients receiving disease-modifying therapies (DMTs) to understand their relationship with treatment duration and functional status.</p><p><strong>Methods: </strong>Our study includes both cross-sectional and longitudinal analyses of myostatin levels in treated SMA patients. The longitudinal cohort included 46 treatment-naive patients assessed at baseline and 12 months post-treatment. Myostatin levels were measured using ELISA. Age-matched controls (n = 89) were included for comparison. The cross-sectional study included 128 patients with variable durations of treatment (from 0.4 to 7.2 years). In both cohorts, myostatin levels were correlated with SMA type, functional status, and clinical outcomes.</p><p><strong>Results: </strong>Baseline myostatin levels were significantly lower than controls (p < 0.001), except during the neonatal period in presymptomatic patients. After 12 months of treatment, there were no significant changes compared to baseline levels (p = 0.1652). The only substantial changes were observed in presymptomatic neonates, who showed a reduction of myostatin despite treatment intervention. There was a significant correlation between myostatin levels, functional status, and SMA type both in the cross-sectional and longitudinal groups.</p><p><strong>Interpretation: </strong>This study demonstrates lower myostatin levels in SMA patients compared to controls. The association between myostatin levels, functional status, and SMA type suggests its possible role as a disease severity biomarker. The utility of myostatin as a biomarker for DMT response remains controversial; while we observed no significant increase in myostatin levels following treatment, we also did not observe the progressive reduction previously reported in untreated patients.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144075051","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":"Reply to Letter: Real-World Clinical Experience With Serum MOG and AQP4 Antibody Testing by Live Versus Fixed Cell-Based Assay.","authors":"Yana Said, Conlan Tran, LuAnn Rezavi, Patrizio Caturegli, Eoin P Flanagan, Elias S Sotirchos","doi":"10.1002/acn3.70061","DOIUrl":"https://doi.org/10.1002/acn3.70061","url":null,"abstract":"","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144075052","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}