Annals of Clinical and Translational Neurology最新文献

{"title":"A Comprehensive Overview of the Clinical, Electrophysiological, and Neuroimaging Features of BPAN: Insights From a New Case Series","authors":"Seda Susgun,&nbsp;Ozgu Kizek,&nbsp;Sibel Aylin Ugur Iseri,&nbsp;Ibrahim Kamaci,&nbsp;Ayse Deniz Elmali,&nbsp;Pinar Iscen,&nbsp;Berfin Gulkaya Guzel,&nbsp;Gul Yalcin Cakmakli,&nbsp;Bulent Elibol,&nbsp;Berril Donmez,&nbsp;Raif Cakmur,&nbsp;Pinar Topaloglu,&nbsp;Turkish NBIA Study Group,&nbsp;Nerses Bebek,&nbsp;Murat Emre,&nbsp;Zuhal Yapici","doi":"10.1002/acn3.70220","DOIUrl":"10.1002/acn3.70220","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Neurodegeneration with brain iron accumulation (NBIA) comprises a genetically and clinically heterogeneous group of rare neurological disorders characterized particularly by iron accumulation in the basal ganglia. To date, 15 genes have been associated with NBIA. Among them, <i>WDR45</i>, linked to beta-propeller protein-associated neurodegeneration (BPAN), represents the only X-linked dominant subtype of NBIA. Herein, clinical, electrophysiological, and neuroimaging evaluations were used to broaden the understanding of BPAN in a newly reported case series.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This study included 10 individuals with BPAN, categorized into three age groups. <i>WDR45</i> variant data retrieved from next-generation sequencing or Sanger sequencing were reviewed and reassessed. Comprehensive clinical evaluations including magnetic resonance imaging (MRI), fluorodeoxyglucose positron emission tomography (FDG-PET), and video electroencephalographic monitoring were conducted.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The clinical manifestations were highly heterogeneous, with cognitive impairment being a consistent finding among the patients, with variable severity. The associated <i>WDR45</i> variants are likely to exert loss-of-function effects. Electroencephalogram (EEG) abnormalities included age-dependent background slowing and epileptiform discharges. MRI indicated a characteristic pattern, while two patients lacked these typical findings. FDG-PET imaging demonstrated hypometabolism extending beyond cerebral structures, with predominant cerebellar and pontine involvement in pediatric patients and frontoparietal hypometabolism in adults.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This study contributes further to our understanding of the heterogeneous clinical spectrum of BPAN. Genotype–phenotype correlation in BPAN remains unclear due to the absence of sufficiently large cohorts in the literature, including the present study. Nevertheless, even within this small sample, the phenotypic heterogeneity observed among individuals harboring the same genotype highlights the biological complexity of the disease. Neuroimaging findings may reflect progressive and widespread neurological involvement in an age-dependent pattern, whereas EEG data suggest that epilepsy severity tends to decrease after adolescence.</p>\u0000 </section>\u0000 </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"13 3","pages":"453-465"},"PeriodicalIF":3.9,"publicationDate":"2026-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12968449/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145297739","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":"Prediction Model for Etiologic Differentiation of Isolated Vestibular Syndrome in Emergency Settings","authors":"Guo Wenting,&nbsp;Du Liping,&nbsp;Yang Yi,&nbsp;Hu Jin,&nbsp;Ye Bijun,&nbsp;Wang Jianer,&nbsp;Liu Shuangsi,&nbsp;Guo Shunyuan,&nbsp;Cai Xiaofeng,&nbsp;Wang Huiyuan,&nbsp;Wu Bin,&nbsp;Yu Xiang,&nbsp;Shi Tianming","doi":"10.1002/acn3.70213","DOIUrl":"10.1002/acn3.70213","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This study aimed to develop and validate a predictive model for differentiating central from peripheral etiologies in patients with isolated vestibular syndrome (VS).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this multicenter retrospective cohort study, 506 patients with isolated VS from five hospitals were divided into derivation (<i>n</i> = 301) and validation (<i>n</i> = 205) cohorts. Multivariable logistic regression was performed to determine independent predictors of central VS. These predictors were assigned weights to construct the SAV₃E score. The performance of the SAV₃E was assessed using the area under the curve (AUC), calibration, and decision curve analysis (DCA) and compared with that of the TriAGe+ and STANDING models.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The SAV₃E score incorporated five predictors: absence of vestibular vagal symptoms (OR, 0.233; 95% CI, 0.084–0.648; <i>p</i> = 0.005), prior stroke (OR, 15.204; 95% CI, 4.455–51.884; <i>p</i> &lt; 0.001), ABCD₂ score of 4–7 (OR, 1.903; 95% CI, 1.206–3.004; <i>p</i> = 0.006), central video oculography nystagmus (OR, 38.377; 95% CI, 8.631–170.644; <i>p</i> &lt; 0.001), and positive video head impulse test (OR, 0.078; 95% CI, 0.033–0.188; <i>p</i> &lt; 0.001). It displayed good discriminative performance with AUCs 0.910 and 0.886 in the derivation and validation cohorts, respectively. It outperformed TriAGe+ (AUC: 0.706) and STANDING (AUC: 0.779) models. Furthermore, calibration analysis revealed good model fit across cohorts (Hosmer-Lemeshow test results: derivation cohort, <i>p</i> = 0.899; validation cohort, <i>p</i> = 0.789). DCA confirmed good clinical utility across a wide range of probability thresholds (derivation cohort: 0.01–0.86, validation cohort: 0.01–1.00).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The SAV₃E score is a validated tool aimed at differentiating central versus peripheral VS, with the potential to improve diagnostic accuracy for urgent etiologies such as stroke.</p>\u0000 </section>\u0000 </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"13 3","pages":"504-516"},"PeriodicalIF":3.9,"publicationDate":"2026-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12968455/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145367225","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":"Accelerated Progression of Gait Impairment in Parkinson's Disease and REM Sleep Without Atonia","authors":"Sommer L. Amundsen-Huffmaster,&nbsp;Jae Woo Chung,&nbsp;Maria E. Linn-Evans,&nbsp;Matthew N. Petrucci,&nbsp;Chiahao Lu,&nbsp;Destiny J. Weaver,&nbsp;Joshua De Kam,&nbsp;Scott E. Cooper,&nbsp;Paul J. Tuite,&nbsp;Aleksandar Videnovic,&nbsp;Michael J. Howell,&nbsp;Colum D. MacKinnon","doi":"10.1002/acn3.70214","DOIUrl":"10.1002/acn3.70214","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>People with Parkinson's disease (PD) and rapid eye movement (REM) sleep without atonia (RSWA) often have more severe gait disturbances compared to PD without RSWA. The association between the presence and expression of RSWA and the rate of progression of gait impairment in PD is unknown. This study examined the changes in spatiotemporal gait metrics over 3 years in people with mild-to-moderate PD (median 1.5 years since diagnosis at baseline) with (PD+RSWA, <i>n</i> = 16) and without RSWA (PD-RSWA, <i>n</i> = 14), and matched controls (<i>n</i> = 16).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Steady-state gait metrics were obtained using a pressure-sensitive walkway at baseline and 3-year follow-up. RSWA scores were measured from electromyographic recordings during video-based polysomnography at baseline. Linear mixed models tested for the effects of visit, group, side (less vs. more affected), and their interactions. In people with PD, Spearman's correlations examined the relationship between baseline RSWA scores and the change in gait metrics.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Stride velocity variability was larger in PD+RSWA, compared to PD-RSWA and controls. Spatial and temporal measures of gait significantly worsened in both PD groups over 3 years. The PD+RSWA group showed a significantly larger decrement in step length (<i>p</i> &lt; 0.05; mean = 7.9%) compared to PD-RSWA (2.6%) and controls (2.3%). Variability measures did not change significantly. In PD, the change in stride length correlated with chin RSWA scores at baseline.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>RWSA in early PD may be a harbinger of a more rapid progression in gait impairment, characterized primarily by a shortening of steps.</p>\u0000 </section>\u0000 </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"13 3","pages":"517-529"},"PeriodicalIF":3.9,"publicationDate":"2026-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12968468/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145385488","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":"Copy Number Variants and Their Association With Intracerebral Hemorrhage Risk: A Case–Control Study","authors":"Savvina Prapiadou,&nbsp;Carl D. Langefeld,&nbsp;Padmini Sekar,&nbsp;Mary Comeau,&nbsp;Timothy Howard,&nbsp;Tamara N. Kimball,&nbsp;Chen Bowang,&nbsp;Hyacinth I. Hyacinth,&nbsp;Jonathan Rosand,&nbsp;Christopher D. Anderson,&nbsp;Caspar Grond-Ginsbach,&nbsp;Daniel Woo,&nbsp;Stacie L. Demel","doi":"10.1002/acn3.70230","DOIUrl":"10.1002/acn3.70230","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Intracerebral Hemorrhage (ICH) is a leading cause of morbidity and mortality worldwide and lacks effective therapeutic interventions. Despite previous studies, the genetic underpinnings of ICH remain poorly understood. We sought to investigate the role of copy number variants (CNVs) in ICH pathophysiology to identify novel etiological mechanisms and therapeutic targets.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We analyzed microarray data from ICH cases and controls using PennCNV software, followed by rigorous quality control and CNV validation. This case–control study explored associations between large, rare CNVs and ICH risk, examining CNVs that are genic, contain ohnologs, or span multiple genes. Functional enrichment analysis was also conducted to identify overrepresented CNVs in biological processes relevant to ICH.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The study included 649 cases and 437 controls who passed quality control. Cases were more likely to have genic CNVs compared to controls (39.6% vs. 32.5%, <i>p</i> value = 0.02) after adjusting for age, sex, hypertension, and admixture. In pathway analysis, CNVs associated with cholesterol biosynthesis (6.3% vs. 3.2%, <i>p</i> value = 0.04) and blood vessel development were more common in cases (8.2% vs. 5.3%, <i>p</i> value = 0.06). While associations were observed at nominal significance (<i>p</i> &lt; 0.05), none withstood correction for multiple comparisons.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Discussion</h3>\u0000 \u0000 <p>Our study represents the first CNV analysis of ICH risk. While significant associations between large, rare CNVs and ICH risk were not established, the findings indicate potential pathways for further research. The identified trends warrant further investigation, and our methodological framework provides a foundation for future large-scale studies aimed at elucidating the role of CNVs in ICH pathogenesis and outcomes.</p>\u0000 </section>\u0000 </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"13 3","pages":"530-536"},"PeriodicalIF":3.9,"publicationDate":"2026-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12968461/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145385544","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 MMP-9/TIMP-1 Ratio and Concentrations of Osteopontin Are Elevated in Cerebrospinal Fluid of People With Multiple Sclerosis and Decrease After Autologous Hematopoietic Stem Cell Transplantation","authors":"Ivan Pavlovic,&nbsp;Ida Erngren,&nbsp;Kim Kultima,&nbsp;Anders Larsson,&nbsp;Malin Müller,&nbsp;Anna Wiberg,&nbsp;Joachim Burman","doi":"10.1002/acn3.70229","DOIUrl":"10.1002/acn3.70229","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>To evaluate the utility of cerebrospinal fluid (CSF) biomarkers—matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinases-1 (TIMP-1), the MMP-9/TIMP-1 ratio, and osteopontin (OPN)—as indicators of blood–brain barrier (BBB) integrity and disease activity in people with relapsing–remitting multiple sclerosis (pwMS), and to assess their changes following autologous hematopoietic stem cell transplantation (aHSCT).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>CSF samples from pwMS treated with aHSCT (<i>n</i> = 43) and healthy controls (<i>n</i> = 32) were analyzed for MMP-9, TIMP-1, and OPN concentrations using ELISA and electrochemiluminescence assays. Lumbar punctures were performed at baseline and at 1, 2, and 3–5 years post-aHSCT. Biomarker findings were compared with standard CSF parameters, prior treatments, and MRI data.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>MMP-9/TIMP-1 ratios and OPN levels were significantly elevated in pwMS compared to controls, particularly in those with gadolinium-enhancing lesions or on first-line therapies. Both biomarkers declined significantly after aHSCT and remained low during follow-up. The MMP-9/TIMP-1 ratio showed superior discriminatory capacity and correlated with inflammatory CSF markers.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>CSF MMP-9/TIMP-1 ratio and OPN are elevated in MS and decrease following aHSCT, reflecting reduced inflammation and restored BBB integrity. These biomarkers may support disease monitoring and therapeutic evaluation.</p>\u0000 </section>\u0000 </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"13 3","pages":"442-452"},"PeriodicalIF":3.9,"publicationDate":"2026-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12968448/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145290500","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 Relationship Between Inflammation and Central Nervous System in Multiple Sclerosis","authors":"Gamze Ansen,&nbsp;Ali Behram Salar,&nbsp;Abdulkadir Ermis,&nbsp;Erkingul Birday,&nbsp;Lutfu Hanoglu,&nbsp;Bayram Ufuk Sakul","doi":"10.1002/acn3.70231","DOIUrl":"10.1002/acn3.70231","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Multiple sclerosis is an autoimmune demyelination disease that is seen especially in the young population and has a progressive course, causing motor, sensory, and cognitive deficits. In the literature, the pathogenesis of MS disease and the interconnection between the immune and central nervous system in the disease have not been fully revealed. Recent studies indicate that gray matter damage, as well as white matter lesions, are frequently seen in MS patients. Based on this background, the present study aimed to explore whether relapsing–remitting MS patients in the attack phase demonstrate different patterns of functional connectivity compared to those in a stable phase.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Material and Method</h3>\u0000 \u0000 <p>For this purpose, resting-state fMRI findings of the attack (<i>n</i> = 5) and stable (<i>n</i> = 14) groups were examined.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Compared to stable patients, the attack group appeared to show increased functional connectivity in several gray matter structures, including the left fusiform, posterior cingulate, orbitofrontal cortex, left supramarginal gyrus, thalamus, and precuneus.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The findings indicate that patients in the inflammatory phase may exhibit increased activation in distinct gray matter regions relative to those not in the attack phase. This pattern might reflect the development of compensatory functional connections aimed at limiting potential clinical damage during relapse. Moreover, considering the diverse roles of these regions, their involvement could hypothetically be linked to immune-related processes, a possibility that warrants further investigation in larger cohorts.</p>\u0000 </section>\u0000 </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"13 3","pages":"488-503"},"PeriodicalIF":3.9,"publicationDate":"2026-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12968467/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145353200","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":"Portable Low-Field Magnetic Resonance Imaging in People With Human Immunodeficiency Virus","authors":"Annabel Sorby-Adams,&nbsp;Malachi Keo,&nbsp;Jennifer Guo,&nbsp;Daire Daly,&nbsp;Richard Ahern,&nbsp;Kimon Zachary,&nbsp;Gregory Robbins,&nbsp;Rajesh T. Gandhi,&nbsp;Bragi Sveinsson,&nbsp;Adam de Havenon,&nbsp;Kevin N. Sheth,&nbsp;Otto Rapalino,&nbsp;Juan Eugenio Iglesias Gonzales,&nbsp;W. Taylor Kimberly,&nbsp;Shibani S. Mukerji","doi":"10.1002/acn3.70237","DOIUrl":"10.1002/acn3.70237","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>The aging population of people with HIV (PWH) raises heightened concerns regarding accelerated aging and dementia. Portable, low-field MRI (LF-MRI) is an innovative technology that could enhance access and facilitate routine monitoring of PWH. We sought to evaluate the feasibility of LF-MRI and apply a machine learning (ML) segmentation algorithm to examine atrophy and white matter hyperintensities (WMH) in PWH compared to people without HIV (PWoH) of similar age.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Individuals with a confirmed diagnosis of HIV on antiretroviral therapy underwent LF-MRI (64 mT) acquisition in the outpatient neurology clinic. PWoH with &gt; 1 vascular comorbidity (VC cohort, <i>n</i> = 25) or with mild cognitive impairment (MCI cohort, <i>n</i> = 24) due to Alzheimer's disease served as comparators. LF-MRI brain region segmentations were derived using the ML algorithm WMH-SynthSeg in FreeSurfer. Brain regions corrected for intracranial volume were compared between cohorts after adjusting for age and sex.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Thirty virally suppressed PWH were included. LF-MRI derived brain volumes from PWH demonstrated a reduction in volume of the caudate relative to PWoH with VC (<i>p</i> &lt; 0.05). Volume of the putamen and white matter was reduced in PWH compared to VC (<i>p</i> &lt; 0.05). Hippocampal volume was comparable between PWH and PWoH (<i>p</i> ≥ 0.05), while volume of the amygdala was reduced in those with MCI alone (<i>p</i> &lt; 0.05). No differences in WMH were seen between these cohorts (<i>p</i> &gt; 0.05).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>LF-MRI is feasible in an outpatient setting, and ML algorithms enable detection of regional atrophy and WMH in PWH. LF-MRI may enable more frequent monitoring and earlier detection of atrophy in at-risk populations.</p>\u0000 </section>\u0000 </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"13 3","pages":"537-546"},"PeriodicalIF":3.9,"publicationDate":"2026-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12968453/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145450432","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":"Insights Into the Antigenic Repertoire of Unclassified Synaptic Antibodies","authors":"Michael Gilligan,&nbsp;John R. Mills,&nbsp;Paulina Vargas,&nbsp;Naveen K. Paramasivan,&nbsp;Connie E. Lesnick,&nbsp;Eati Basal,&nbsp;Surendra Dasari,&nbsp;James P. Fryer,&nbsp;Shannon R. Hinson,&nbsp;Joseph Laporta,&nbsp;Amy Espinal,&nbsp;Dennis Fitzgerald,&nbsp;Carolina Garcia,&nbsp;Anna E. Morenkova,&nbsp;Paola Pergami,&nbsp;Anna Shah,&nbsp;Andrew Knight,&nbsp;Reghann LaFrance Corey,&nbsp;Vanda A. Lennon,&nbsp;Anastasia Zekeridou,&nbsp;Sean J. Pittock,&nbsp;Divyanshu Dubey,&nbsp;Andrew McKeon","doi":"10.1002/acn3.70238","DOIUrl":"10.1002/acn3.70238","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>We sought to characterize the sixth most common finding in our neuroimmunological laboratory practice (tissue assay-observed unclassified neural antibodies [UNAs]), combining protein microarray and phage immunoprecipitation sequencing (PhIP-Seq).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Patient specimens (258; 133 serums; 125 CSF) meeting UNA criteria were profiled; October 2022–September 2023. Top-ranking candidate antigens were validated in silico, by dual-staining confocal microscopy, and ≥ 1 protein-specific assay. Clinical data were reviewed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among 21 patients, 11 autoantibodies were characterized (serum, 19; CSF, all 9 available). Autoantigens were CACNA1I, 1; CAMK2B, 2; CLIP2, 1; FMN2, 2; MAP1A, 2; MAP2, 5; NECAB1, 1; SNAP91, 3; SRCIN1, 1; SYNJ1, 1; SYT3, 2. Analytical validation was by confocal TIIFA (all), western blot (10/10 available), and cell-based assay (5/5 performed). Clinical accompaniments were: encephalitis, 6; brainstem encephalitis, 2; encephalomyelitis, 2; cerebellar ataxia, 2; longitudinally extensive transverse myelitis (LETM), 2; sensory neuronopathy, 1; peripheral neuropathy, 4, and movement disorders, 2. Inflammatory MRI abnormalities were identified in 5/16 patients (31%) with CNS disorders: T2 signal change (2), LETM (2), leptomeningeal enhancement (1). Seven of 8 (88%) had inflammatory CSF (pleocytosis, 5 [median 25.5 cells, range 7–294]; elevated IgG index/synthesis rate, 4; CSF-exclusive oligoclonal bands, 4). Six had paraneoplastic causation (lung cancer, 2; other, 4); 3 were postinfectious (1 each of COVID-19, HSV-1, and post-Group A streptococcal infection). Of 9 immunotherapy-treated patients, 5 improved.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>UNAs are partly accounted for by a repertoire of diverse mostly intracellular synaptic antigens. Their characterization is expedited by protein arrays and PhIPSeq. Further individual studies are needed to assess them as disease biomarkers.</p>\u0000 </section>\u0000 </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"13 3","pages":"547-561"},"PeriodicalIF":3.9,"publicationDate":"2026-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12968444/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145450382","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":"Sex Hormones Associate With Amyotrophic Lateral Sclerosis Risk and Survival","authors":"Stephen A. Goutman,&nbsp;David G. Stouffer,&nbsp;Dae-Gyu Jang,&nbsp;Jihyun Park,&nbsp;Benjamin J. Murdock,&nbsp;Richard J. Auchus","doi":"10.1002/acn3.70281","DOIUrl":"10.1002/acn3.70281","url":null,"abstract":"<p>Amyotrophic lateral sclerosis (ALS) risk differs by sex and age, implicating sex hormones as potential modifiers. This study examined plasma levels of biologically active sex hormones and their association with ALS odds and survival in cases (females <i>n</i> = 131, males <i>n</i> = 189) and controls (females <i>n</i> = 138, males <i>n</i> = 150) from the University of Michigan Pranger ALS Clinic. Higher 11-ketotestosterone levels were associated with increased ALS odds. In females, higher estrone, androstenedione, and 11-hydroxyandrostenedione were associated with increased ALS odds, while elevated estrone and estradiol predicted shorter survival. These findings highlight the potential significance of sex hormones in ALS.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"13 3","pages":"612-617"},"PeriodicalIF":3.9,"publicationDate":"2026-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12968447/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145779755","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 Impact of Tilburg Frailty on Poststroke Fatigue in First-Ever Stroke Patients: A Cross-Sectional Study With Unified Measurement Tools and Improved Statistics","authors":"Chuan-Bang Chen,&nbsp;Xiao-Xue Wang,&nbsp;Shao-Rui Bao,&nbsp;Sui-Li Lin,&nbsp;Mei-Chun Shu,&nbsp;Xi-Xi Ye,&nbsp;Wen-Jie Cong","doi":"10.1002/acn3.70202","DOIUrl":"10.1002/acn3.70202","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Poststroke fatigue (PSF) and frailty share substantial overlap in their manifestations, yet previous research has yielded conflicting results due to the use of heterogeneous frailty assessment tools.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To evaluate the independent impact of frailty on PSF using a unified measurement system (Tilburg Frailty Indicator, TFI) while controlling for modified Rankin Scale (mRS), National Institutes of Health Stroke Scale (NIHSS), anxiety, depression, and other confounding factors.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A single-center cross-sectional study was conducted with 320 first-ever stroke patients. Frailty was assessed using the TFI, fatigue with the Fatigue Severity Scale (FSS), and psychological symptoms with the Hospital Anxiety and Depression Scale (HADS). Both linear regression and logistic regression models were employed, with quantile regression for robustness testing.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>TFI total score demonstrated a strong positive correlation with FSS scores (<i>ρ</i> = 0.85, <i>p</i> &lt; 0.001). Here, frailty (independent variable) was captured by TFI and poststroke fatigue (dependent variable) by FSS. In multivariable regression analysis, TFI (<i>β</i> = 0.42, 95% CI: 0.35–0.49), HADS-A (<i>β</i> = 0.28, 95% CI: 0.21–0.35), and NIHSS (<i>β</i> = 0.18, 95% CI: 0.11–0.25) emerged as significant predictors of PSF (all <i>p</i> &lt; 0.001). The combined model explained 74.2% of variance in fatigue scores.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The use of the unified frailty assessment tool (TFI) resolves previous conflicting findings and confirms that frailty is a strong independent predictor of PSF. Routine frailty assessment using the TFI should be incorporated into poststroke care to identify patients at high risk for fatigue and guide targeted interventions.</p>\u0000 </section>\u0000 </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"13 3","pages":"476-487"},"PeriodicalIF":3.9,"publicationDate":"2026-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12968438/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145342216","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}