Neurology® Neuroimmunology & Neuroinflammation最新文献

{"title":"Beyond the Lab Slip: Why Laboratory Expertise Matters in Neuronal Antibody Testing and Why Clinicians Should Care.","authors":"Frank Leypoldt","doi":"10.1212/NXI.0000000000200425","DOIUrl":"10.1212/NXI.0000000000200425","url":null,"abstract":"","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"12 4","pages":"e200425"},"PeriodicalIF":7.8,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12094786/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144111487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pro-Inflammatory Molecules Implicated in Multiple Sclerosis Divert the Development of Human Oligodendrocyte Lineage Cells.","authors":"Gabriela J Blaszczyk, Abdulshakour Mohammadnia, Valerio E C Piscopo, Julien Sirois, Qiao-Ling Cui, Moein Yaqubi, Thomas M Durcan, Raphael Schneider, Jack P Antel","doi":"10.1212/NXI.0000000000200407","DOIUrl":"10.1212/NXI.0000000000200407","url":null,"abstract":"<p><strong>Background and objectives: </strong>Oligodendrocytes (OLs) and their myelin-forming processes are lost during the disease course of multiple sclerosis (MS), targeted by infiltrating leukocytes and their effector cytokines. Myelin repair is considered to be dependent on recruitment and differentiation of oligodendrocyte progenitor cells (OPCs). The basis of remyelination failure during the disease course of MS remains to be defined. The aim of this study was to determine the impact of the proinflammatory molecules tumor necrosis factor-⍺ (TNF⍺) and interferon-<i>γ</i> (IFN<i>γ</i>) on the differentiation of human OPCs.</p><p><strong>Methods: </strong>We generated human OPCs from induced pluripotent stem cells with a reporter gene under the OL-specific transcription factor SOX10. We treated the cells in vitro with TNF⍺ or IFN<i>γ</i> and evaluated effects regarding cell viability, expression of OL lineage markers, and coexpression of astrocyte markers. To relate our findings to the molecular properties of OPCs as found in the MS brain, we reanalyzed publicly available single-nuclear RNA sequencing (RNAseq) datasets.</p><p><strong>Results: </strong>Our analysis indicated that both TNF⍺ and IFN<i>γ</i> decreased the proportion of cells differentiating into the OL lineage, consistent with previous reports. Uniquely, we now observe that the TNF⍺ effect is linked to aberrant OPC differentiation in that a subset of O4+, reporter-positive cells coexpressing the astrocytic marker aquaporin-4. At the transcriptomic level, the cells acquire an astrocyte-like signature alongside a conserved reactive phenotype while downregulating OL lineage genes. Analysis of single-nuclear RNAseq datasets from the human MS brain revealed a subset of OPCs expressing an astrocytic signature.</p><p><strong>Discussion: </strong>In the context of MS, these results imply that OPCs are present but inhibited from differentiating along the OL lineage, with a subset acquiring a reactive and stem cell-like phenotype, reducing their capacity to contribute toward repair. These findings help define a potential basis for the impaired myelin repair in MS and provide a prospective route for regenerative treatment.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"12 4","pages":"e200407"},"PeriodicalIF":7.8,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12094787/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144111488","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Temporal Lobe Epilepsy Associated With Glutamic Acid Decarboxylase Antibodies: Defining a Distinct Epilepsy Syndrome.","authors":"Anna Rada, Lea Marie Reisch, Anne Hagemann, Friedrich G Woermann, Christian G Bien","doi":"10.1212/NXI.0000000000200422","DOIUrl":"10.1212/NXI.0000000000200422","url":null,"abstract":"<p><strong>Background and objectives: </strong>Epilepsy associated with glutamic acid decarboxylase antibodies (GAD-abs) often presents as temporal lobe epilepsy (TLE). However, detailed data on this condition are lacking. The aim of this study was to demonstrate that TLE with GAD-abs (GAD-TLE) is distinct from other forms of TLE and to describe the subgroup of patients with epilepsy and GAD-abs but no evidence of TLE.</p><p><strong>Methods: </strong>Inpatients from 2011 to 2022 with high serum GAD-abs (≥1:80, confirmed by a cell-based assay and typical staining pattern on a tissue-based assay) were included. The control group comprised patients with mesial TLE (EMU-mTLE) with hippocampal sclerosis or nonlesional epilepsy diagnosed on the epilepsy monitoring unit (EMU) and having negative results on a broad panel of neural antibodies. Data were retrospectively collected from first admission (visit 1 [V1]) and most recent follow-up (visit 2 [V2]). Parameters included demographic data, comorbidities, seizure characteristics, electroencephalography findings, MRI results, verbal memory performance, GAD-ab titers (V1), therapies, seizure and memory outcomes, and occupational status (V2).</p><p><strong>Results: </strong>Of 81 GAD-ab-positive patients, 71 (88%) had TLE. Compared with 40 EMU-mTLE controls, patients with GAD-TLE were more often female (84% vs 33%, <i>p</i> < 0.001), more frequently had autoimmune comorbidities (46% vs 2.5%, <i>p</i> < 0.001), musicogenic seizures (18% vs 0%, <i>p</i> = 0.004), and seizure clusters (25% vs 5%, <i>p</i> = 0.002) but less frequently had hippocampal sclerosis (25% vs 54%, <i>p</i> = 0.007). At follow-up (GAD-TLE: median 5 years; EMU-mTLE: 2 years), only 14% of patients with GAD-TLE were terminally seizure-free for ≥1 year, compared with 39% of patients with EMU-mTLE (<i>p</i> = 0.04). Verbal memory remained stable, and occupational status was unchanged. Ten GAD-ab-positive cases without evidence of TLE were identified, including 3 with generalized features.</p><p><strong>Discussion: </strong>Epilepsy associated with GAD-abs predominantly manifests as TLE and as such is an epilepsy syndrome (GAD-TLE). In comparison with EMU-confirmed patients with mTLE without GAD-abs, the seizure outcome is inferior but the neuropsychological performance is usually normal and remains stable. A subset of patients with epilepsy with high-titer GAD-abs do not have TLE, some presenting with generalized features.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"12 4","pages":"e200422"},"PeriodicalIF":7.8,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12166559/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144285784","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessing Commercial Tissue-Based Assays for Autoimmune Neurologic Disorders (I): Antibodies to Intracellular Antigens.","authors":"Chiara Milano, Pietro Businaro, Claudia Papi, Lionel Arlettaz, Laura Marmolejo, Laura Naranjo, Matteo Gastaldi, Raffaele Iorio, Albert Saiz, Jesús Planagumà, Esther Aguilar, Chiara Pizzanelli, Eugenia Martinez-Hernandez, Thaís Armangué, Mar Guasp, Raquel Ruiz-García, Lidia Sabater, Josep O Dalmau, Francesc Graus, Marianna Spatola","doi":"10.1212/NXI.0000000000200410","DOIUrl":"10.1212/NXI.0000000000200410","url":null,"abstract":"<p><strong>Background and objectives: </strong>Current strategies to detect autoantibodies against intracellular neural antigens (IC-Abs) include tissue-based assays (TBAs) alongside line blots or cell-based assays (CBAs). Many clinical laboratories use commercially available TBAs as a screening test, but their diagnostic yield has not been assessed. We determined the performance of 2 commercial TBAs in detecting IC-Abs.</p><p><strong>Methods: </strong>We analyzed samples from 100 patients with autoimmune or paraneoplastic neurologic syndromes harboring IC-Abs (confirmed by in-house TBAs and line blots or CBAs) and 50 negative controls. IC-Abs samples included serum (10 each for Hu, Yo, Ri, SOX1, CV2, Ma2, Tr, amphiphysin, and GAD65 antibodies) or CSF (10 with GFAP antibodies) samples. Two commercial indirect immunofluorescence (IIF) TBAs (INOVA and EUROIMMUN) were assessed by 2 experienced investigators and 3 less experienced raters, all blinded to antibody status. Discordant results were re-evaluated through interrater discussion and assessed using Cohen's kappa.</p><p><strong>Results: </strong>The 2 experienced raters showed substantial agreement (85% for INOVA, 83% for EUROIMMUN) on negative/positive results, which increased to >95% after interrater discussion (Cohen's kappa 0.95 and 0.93, respectively). With IIF-INOVA, they correctly identified 118 of 150 samples (79%) and misclassified 28 of 150 (19%, 2 false positives and 26 false negatives) while results remained discordant in the remaining 4 of 150 samples (2%). With IIF-EUROIMMUN, they correctly identified 105 of 150 samples (70%) and misclassified 40 of 150 (27%, 6 false positives, 34 false negatives), with discordance in 5 of 150 samples (3%). Overall, the sensitivity was 73% for IIF-INOVA and 66% for IIF-EUROIMMUN. The specificity was 96% for IIF-INOVA and 88% for IIF-EUROIMMUN. Both TBAs showed low sensitivity in detecting CV2, SOX1, and amphiphysin antibodies while Ma2 antibodies were missed mainly by IIF-EUROIMMUN and Hu/Ri antibodies by IIF-INOVA. Antibody-specific immunostaining patterns were correctly identified in 62 of 100 positive samples with IIF-INOVA and 55 of 100 with IIF-EUROIMMUN (<i>p</i> = 0.34). Less experienced raters showed higher rates of false-positive results (up to 22% with IIF-EUROIMMUN).</p><p><strong>Discussion: </strong>The performance of commercial IIF-TBAs for IC-Abs detection is suboptimal, exhibiting high false-negative rates of 25%-35%. Therefore, commercial TBAs should not be used alone for IC-Abs screening, but alongside more sensitive techniques, such as line blots. Discordant results between 2 techniques should prompt retesting in reference centers with in-house TBAs, particularly when the suspicion of an autoimmune or paraneoplastic syndrome is high.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"12 4","pages":"e200410"},"PeriodicalIF":7.8,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12153943/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144111485","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bruton Tyrosine Kinase in Lesions of Multiple Sclerosis and 3 of Its Models.","authors":"Cenxiao Li, Marlene T Morch, Rianne Gorter, Brian Lozinski, Samira Ghorbani, Yifei Dong, Yun-An Shen, Christopher Harp, Stephanie Zandee, Wendy Klement, Alexandre Prat, V Wee Yong","doi":"10.1212/NXI.0000000000200413","DOIUrl":"10.1212/NXI.0000000000200413","url":null,"abstract":"<p><strong>Background and objectives: </strong>The pathophysiology of multiple sclerosis (MS) is contributed by B lymphocytes, macrophages, and microglia. Bruton tyrosine kinase (BTK) is an intracellular enzyme within these cells that modulates their inflammatory properties. Thus, central nervous system-penetrant inhibitors of BTK may counter immune dysregulation, and this aspiration is highlighted by 11 phase 3 clinical trials in MS to inhibit this enzyme. Despite the keen interest, the spatial and temporal elevation of BTK in lesions of MS and its models is not well characterized.</p><p><strong>Methods: </strong>We used quantitative fluorescence immunohistology to assess the expression of BTK and a phosphorylated activated form in different lesion types of MS and 3 of its models: inflammatory experimental autoimmune encephalomyelitis (EAE), toxin-induced demyelination of lysolecithin, and oxidized phosphatidylcholine injuries. GDC-0853 (fenebrutinib), a BTK inhibitor in phase 3 clinical trials in MS, was evaluated in EAE for its capacity to alter disease course.</p><p><strong>Results: </strong>We observed low expression of BTK and a phosphorylated form (pBTK) in murine spinal cord but significant upregulation in white matter lesions inflicted by oxidized phosphatidylcholine, lysolecithin, and EAE. Expression predominantly localized to microglia/macrophages shown through colocalization analysis by Imaris 3-dimensional rendering. GDC-0853 (fenebrutinib) significantly reduced clinical severity of EAE when administered prophylactically and marginally ameliorated disability when initiated from onset of clinical disability. Finally, we report the increase in BTK expression in microglia/macrophages in active plaques and in the hypercellular rim of chronic active lesions of MS. In the inactive core of chronic active MS lesions, the few remaining HLA-DR⁺ myeloid cells were still BTK immunoreactive.</p><p><strong>Discussion: </strong>Our results demonstrate that BTK immunoreactivity is normally undetectable in uninjured areas or normal-appearing white matter of human and murine CNS, but that expression becomes prominent in lesions with hypercellular aggregates of microglia and macrophages. Staining for pBTK reveals that its upregulation declines in the later stage of lysolecithin and chronic stage of EAE injury while BTK upregulation is maintained. Our collective results support the rationale of using brain-penetrant BTK inhibitors to modulate the elevation of this enzyme in microglia/macrophages within inflamed plaques of MS.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"12 4","pages":"e200413"},"PeriodicalIF":7.8,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12153947/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144180886","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rituximab Use for Relapse Prevention in Anti-NMDAR Antibody-Mediated Encephalitis: A Multicenter Cohort Study.","authors":"Nabil Seery, Robb Wesselingh, Paul Beech, Laurie McLaughlin, Tiffany Rushen, Amy J Halliday, Liora Ter Horst, Sarah P Griffith, Mirasol Forcadela, Tracie H Tan, Christina Kazzi, Cassie Nesbitt, James Broadley, Katherine Buzzard, Andrew Duncan, Wendyl J D'Souza, Yang Tran, Anneke Van Der Walt, Genevieve Skinner, Bruce V Taylor, Andrew Swayne, Amy Brodtmann, David Gillis, Ernest Gerard Butler, Tomas Kalincik, Udaya K Seneviratne, Richard A Macdonell, Stefan Blum, Sudarshini Ramanathan, Charles B Malpas, Stephen W Reddel, Todd A Hardy, Terence J O'Brien, Paul G Sanfilippo, Helmut Butzkueven, Mastura Monif","doi":"10.1212/NXI.0000000000200395","DOIUrl":"10.1212/NXI.0000000000200395","url":null,"abstract":"<p><strong>Background and objectives: </strong>Rituximab is an anti-CD20 monoclonal antibody used in patients with anti-NMDAR antibody (Ab)-mediated encephalitis as both an acute escalation therapy and a longer term relapse risk-reduction treatment. The potential long-term benefit of a single course administered during the acute disease phase on future relapse risk is uncertain. Moreover, the optimal dosing duration to reduce relapse risk is unknown. The aim of this study was to evaluate the effect of a single course of rituximab on relapse incidence. We also studied the duration of effect of a course of rituximab in adult patients with anti-NMDAR Ab-mediated encephalitis.</p><p><strong>Methods: </strong>We recruited 67 patients with anti-NMDAR Ab-mediated encephalitis from 10 Australian hospitals. Rituximab exposure was quantified as a time-varying covariate in Cox proportional hazard models.</p><p><strong>Results: </strong>A single course of rituximab was associated with longer time to first relapse (hazard ratio [HR] 0.11, 95% CI 0.02-0.70, <i>p</i> = 0.02). For patients in whom redosing is considered, rituximab was associated with longer time to first relapse at 6 months after the last infusion, after adjusting for concurrent immunotherapies and the presence of ovarian teratoma at disease onset (HR 0.05, 95% CI 0.00-0.48, <i>p</i> = 0.005). The treatment effect did not persist out to 12 months after a given course (HR 0.60, 95% CI 0.15-2.44, <i>p</i> = 0.47).</p><p><strong>Discussion: </strong>A single course of rituximab reduces the risk of relapse of anti-NMDAR antibody-mediated encephalitis. In select patients for whom redosing of rituximab is considered, administration at 6 months delays relapses.</p><p><strong>Classification of evidence: </strong>This study provides Class IV evidence that rituximab delays relapses in patients with anti-NMDAR antibody-mediated encephalitis.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"12 4","pages":"e200395"},"PeriodicalIF":7.8,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12153942/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144187458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the Clinical Utility of Neurofilament Light Chain Assays in Multiple Sclerosis Management.","authors":"Amit Bar-Or, Jacqueline Nicholas, Jenny Feng, Francesca Sorrell, Mark Cascione","doi":"10.1212/NXI.0000000000200427","DOIUrl":"10.1212/NXI.0000000000200427","url":null,"abstract":"<p><p>Multiple sclerosis (MS) is a chronic neuroinflammatory and neurodegenerative disease that affects nearly 1 million adults in the United States. Owing to its unpredictable disease course, diverse phenotypes, and an array of currently available disease-modifying therapies, a personalized approach to MS management is required. There is an unmet need to identify, validate, and incorporate prognostic, monitoring, and predictive biomarkers into routine clinical practice for MS. A mounting body of evidence supports the use of blood biomarkers, such as neurofilament light chain (NfL), in predicting disease activity and monitoring treatment response. Previous hurdles for the widespread use of NfL in the clinical management of patients, such as invasive sampling methods and limited assay availability, are being overcome through the development and validation of new commercial serum NfL (sNfL) assays. With rising availability, there is now potential for incorporating sNfL testing to support traditional clinical assessments such as MRI, relapse rates, and disability progression measurements. However, clinical and technical limitations to the interpretation of NfL, such as comorbidities, and lack of measurement standardization and well-established reference ranges still pose challenges to its use. Based on the most recent evidence, this review aims to educate healthcare professionals on the potential utility of NfL in the clinical management of people living with MS and provide practical information on the development and availability of new assays.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"12 4","pages":"e200427"},"PeriodicalIF":7.8,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12185222/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144326408","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Features of Children With MOG-IgG Who Fulfill Criteria of Multiple Sclerosis and Overlapping Disorders.","authors":"Elianet Gisell Fonseca, Gemma Olivé-Cirera, Li-Wen Chen, Fernando Paredes-Carmona, Noemí Nuñez Enamorado, Sabas Boyero Duran, Maria Del Mar Mendibe, Núria Visa-Reñé, María Vázquez-López, Ana Felipe-Rucián, Gemma Romeu, Eugenia Martinez-Hernandez, Yolanda Blanco, Maria Sepulveda, Albert Saiz, Josep Dalmau, Thaís Armangue","doi":"10.1212/NXI.0000000000200400","DOIUrl":"10.1212/NXI.0000000000200400","url":null,"abstract":"<p><strong>Objectives: </strong>The aim of this study was to report the clinical features, disease-modifying treatment (DMT) response, and outcomes of children with MOG-IgG who fulfill the 2017 McDonald criteria for multiple sclerosis (MS).</p><p><strong>Methods: </strong>This prospective observational study included children (<18 years) with a suspected acquired demyelinating syndrome (ADS) whose serum or CSF was positive for MOG-IgG, who met the indicated MS criteria, and who had ≥1 year of clinical follow-up. MOG-IgG was tested using live cell-based assays.</p><p><strong>Results: </strong>Of 554 children with confirmed ADS (196 with MOG-IgG), 8 (median age 11 years, interquartile range 9-14) harbored MOG-IgG and fulfilled MS criteria: 2 had typical MS and 6 had overlapping MOGAD-MS features at onset, but 5 of the latter group developed an MS-like course during follow-up. Five of 7 patients with assessable samples were Epstein-Barr virus seropositive at disease onset, and all 8 had persistent silent radiologic activity with lesional location and morphology suggestive of MS, leading to initiation of DMT. All initial treatments were well tolerated, but eventually, 7 of 8 children (88%) required high-efficacy DMT.</p><p><strong>Discussion: </strong>In this pediatric cohort, 4% of patients with MOG-IgG met criteria for MS. The clinical-radiologic spectrum ranged from typical MS to overlapping MOGAD-MS, and patients usually required high-efficacy DMT.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"12 4","pages":"e200400"},"PeriodicalIF":7.8,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12166555/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144285783","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retinal Optical Coherence Tomography Longitudinal Measures as Prognostic Biomarkers in Multiple Sclerosis: Systematic Review and Meta-Analysis.","authors":"Nabil K El Ayoubi, Ali Ismail, Georgio Sader, Nour Abi Chakra, Jad El Ahdab, Joseph Abboud, Samia J Khoury","doi":"10.1212/NXI.0000000000200416","DOIUrl":"10.1212/NXI.0000000000200416","url":null,"abstract":"<p><strong>Background and objectives: </strong>Optical coherence tomography (OCT) has emerged as a valuable marker for assessing inflammation and neuroaxonal degeneration in multiple sclerosis (MS). Although traditional markers such as brain atrophy and axonal loss are crucial for monitoring MS progression, their clinical application can be limited by various factors. This meta-analysis of longitudinal studies aims to assess the predictive value of OCT-derived retinal layer thickness thresholds for monitoring and predicting MS disease progression and cognitive decline.</p><p><strong>Methods: </strong>Our systematic review and meta-analysis followed Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. A comprehensive systematic search was performed using electronic databases (PubMed, Embase, Web of Science, and Google Scholar) for longitudinal studies using Spectral Domain-OCT (SD-OCT) to assess retinal layer thickness and its predictive value for MS progression. Data were extracted on study design, OCT measurements, disability progression definitions, and clinical outcomes. We analyzed hazard ratios (HR) and odds ratios (OR) for associations between OCT-measured thresholds and disability progression, including physical and cognitive deterioration.</p><p><strong>Results: </strong>Our study included 14 longitudinal studies that met our inclusion criteria, 13 studies were included in our quantitative analysis, with a total of 3,683 participants. Baseline peripapillary retinal nerve fiber layer (pRNFL) thickness below 88 μm was significantly associated with increased risk of future disease progression and physical worsening measured by Expanded Disability Status Scale progression (HR = 2.376, <i>p</i> < 0.001; HR = 2.258, <i>p</i> < 0.001, respectively). The same was noted for ganglion cell-inner plexiform layer (GCIPL) thickness below 77 μm (HR = 2.751, <i>p</i> < 0.001 and HR = 2.66, <i>p</i> < 0.001, respectively). In addition, annualized rates of pRNFL thinning above 1.5 μm/y and GCIPL thinning above 1 μm/y also significantly predicted disease worsening (HR = 3.019, <i>p</i> = 0.005 and HR = 3.535, <i>p</i> < 0.001, respectively).</p><p><strong>Discussion: </strong>OCT-derived retinal layer thresholds, specifically a pRNFL thickness of ≤88 μm and a GCIPL thickness of ≤77 μm, are significantly associated with an increased risk of future MS disability progression. Furthermore, annual thinning rates of pRNFL >1.5 μm/y and GCIPL >1 μm/y demonstrate greater predictive power and are more clinically relevant for identifying individuals at high risk of both physical and cognitive disability progression outcomes. Further research is needed to standardize OCT thresholds and improve clinical use in treatment planning.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"12 4","pages":"e200416"},"PeriodicalIF":7.8,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12153945/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144160625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extracellular Vesicle-Derived MicroRNAs as a Biomarker for Therapeutic Response in Multiple Sclerosis.","authors":"Gabriel Torres-Iglesias, MariPaz López-Molina, Rubén Ayala-Suárez, Beatriz Egido, Fernando Laso-García, Beatriz Chamorro, Inmaculada Puertas, Mireya Fernández-Fournier, Ana Montero-Calle, Rodrigo Barderas, Elisa Alonso-López, Exuperio Díez-Tejedor, María Gutiérrez-Fernández, Laura Otero Ortega","doi":"10.1212/NXI.0000000000200420","DOIUrl":"10.1212/NXI.0000000000200420","url":null,"abstract":"<p><strong>Background and objectives: </strong>Multiple sclerosis (MS) is the leading cause of neurologic disability in young adults worldwide. Despite the development of 20 disease-modifying treatments (DMTs) aimed at reducing disability, approximately 30% of patients experience therapeutic failure. Identifying early biomarkers for therapeutic response is, therefore, essential to enhance the rate of therapeutic effectiveness. As such, this study aims to investigate the role of circulating extracellular vesicles (EVs) as early biomarkers for clinical parameters associated with treatment response in patients with MS.</p><p><strong>Methods: </strong>We conducted an observational study involving patients with MS initiating a new DMT. Levels, size, and microRNA content of EVs derived from neurons (L1CAM⁺), oligodendrocytes (MOG⁺), and B (CD20⁺) and T (CD3⁺) cells were assessed both before and at 3 months after treatment initiation. Their correlation with therapeutic response over 12 months in patients with MS was also analyzed. The response to treatment was evaluated using the No Evidence of Disease Activity composite (NEDA), which includes clinical relapses, new lesions on MRI, progression of motor and cognitive disability, and brain atrophy.</p><p><strong>Results: </strong>The levels and size of CD3⁺ and L1CAM⁺ EVs correlated with relapses, new lesions on MRI, and progression of motor disability while the CD20⁺ EV subpopulation reflected cognitive impairment. MicroRNA sequencing demonstrated differential expression of miR-28-3p, miR-326, miR-98-5p, miR-144-5p, miR-98-3p, miR-23a-3p, and miR-146a-5p in responders and non responders. miR-186-5p expression correlated negatively with brain atrophy. Combining EV levels and microRNA expression provided an early and robust model for therapeutic response, with significant correlations enhancing the model's accuracy.</p><p><strong>Discussion: </strong>This study underscores the potential of specific EV characteristics and microRNA content as early biomarkers for treatment response in patients with MS. The downregulation of specific microRNAs emerges as a promising indicator of favorable clinical outcomes, thereby suggesting their utility in early therapeutic decision making. Notably, our findings regarding miR-186-5p as a biomarker for brain atrophy represent a novel contribution to the field. Overall, early EV levels and microRNA content analysis at 3 months after treatment initiation seem to be promising as regards anticipating irreversible neurologic damage, thereby offering a valuable tool for optimizing MS treatment management.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"12 4","pages":"e200420"},"PeriodicalIF":7.8,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12185221/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144333578","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}