Neurology® Neuroimmunology & Neuroinflammation最新文献

{"title":"Clinical Characterization and Long-Term Outcome in Children and Adults With Anti-AMPA Receptor Encephalitis.","authors":"Chiara Milano, Ezgi Saylam, Claudia Papi, Laura Marmolejo, Alexandra Sankovic, Raphael Reinecke, Jeroen Kerstens, Chiara Pizzanelli, Mateus Mistieri Simabukuro, Marie Benaiteau, Bastien Joubert, Matteo Gastaldi, Lívia Almeida Dutra, Frank Leypoldt, Mareike Jansen, Izumi Kawachi, Hisanao Akiyama, Nikolas Boy, Silvia Bozzetti, Peter Broegger Christensen, Pietro Businaro, Alessandro Dinoto, Tal Friedman-Korn, Urara Fujiwara, Tatsuya Fukumoto, Kenshiro Fuse, Sam Ishmael Hooshmand, Lauren Hurst, Raffaele Iorio, Isabelle Korn-Lubetzki, André Filipe Lucchi Rodrigues, Sara Mariotto, Johannes Michael, Yuko Morimoto, Rinze Frederik Neuteboom, Amanda L Piquet, Andrea O Rossetti, Sabine Rumpler-Kreiner, Jonathan D Santoro, Florian Schwendinger, Brenda Shen, Steffen Syrbe, Johannes Troger, Ingrid Wagner, Christian G Bien, Eugenia Martinez-Hernandez, Thais Armangue, Romana Höftberger, Takahiro Iizuka, Maarten J Titulaer, Jerome Honnorat, Francesc Graus, Josep O Dalmau, Setty Magaña, Marianna Spatola","doi":"10.1212/NXI.0000000000200453","DOIUrl":"10.1212/NXI.0000000000200453","url":null,"abstract":"<p><strong>Background and objectives: </strong>Anti-alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor (anti-AMPAR) encephalitis manifests as limbic encephalitis in adults and is often associated with cancer. Although some reports suggest that it may occur in children, the clinical features in this population, as well as the prognostic factors and long-term outcomes in children and adults, are unknown.</p><p><strong>Methods: </strong>We performed a retrospective, international collaborative study of patients with anti-AMPAR encephalitis. Clinical information was reviewed, together with data from published pediatric patients. Clinical features of children and adults were compared with nonparametric tests. Survival rates (Kaplan-Meier curves) were compared using log-rank tests. Prognostic factors of poor outcome (modified Rankin Scale score >2) were identified using logistic regression models.</p><p><strong>Results: </strong>A total of 115 patients were included, of whom 84 (71 adults, 13 children) had only AMPAR antibodies and 31 (27 adults, 4 children) had additional concurrent neural antibodies. Among patients with AMPAR antibodies alone, tumors were identified in 37 adults (56%) and none of the children (<i>p</i> < 0.0001). Children were more likely than adults to have behavioral/psychiatric symptoms (5/13, 39%, vs 8/71, 11%, <i>p</i> = 0.026) at onset, cerebellar dysfunction (6/13, 46%, vs 7/68, 10% <i>p</i> = 0.005) or movement disorders (5/13, 39%, vs 8/67, 12%, <i>p</i> = 0.032) during the disease course, and extratemporal brain MRI lesions (4/9, 44%, vs 5/44, 11%, <i>p</i> = 0.035). Among 34 patients with prolonged follow-up (>24 months), long-term neurocognitive sequelae were reported in 23 (68%), all adults. Failure to respond to first-line immunotherapy at multivariable analysis predicted a poor outcome (OR 8.0, 95% CI 1.1-59.2, <i>p</i> = 0.043). Among the 31 patients with concurrent neural autoantibodies, 22 (79%) had a tumor; those with high-risk antibodies had lower survival rates (<i>p</i> = 0.008).</p><p><strong>Discussion: </strong>Children and adults with anti-AMPAR encephalitis show distinct clinical-radiologic features. At long-term follow-up, 68% of patients, all adults, have neurologic sequelae, with failure to respond to first-line immunotherapy being associated with worse outcomes.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"12 5","pages":"e200453"},"PeriodicalIF":7.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12275903/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144663973","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":"Autologous Hematopoietic Stem Cell Transplantation for Paraneoplastic Cerebellar Degeneration.","authors":"Victor Guerra, Jose Maria Cabrera-Maqueda, Raquel Ruiz-Garcia, Juan Francisco Luchoro, Elianet Fonseca, Mar Guasp, Yolanda Blanco, Maria Suarez-Lledo, Francesc Fernandez-Aviles, Carmen Martinez, Montserrat Rovira, Josep Dalmau, Francesc Graus, Albert Saiz, Eugenia Martinez-Hernandez","doi":"10.1212/NXI.0000000000200433","DOIUrl":"10.1212/NXI.0000000000200433","url":null,"abstract":"<p><strong>Background and objectives: </strong>The aim of this study was to describe 2 patients with paraneoplastic cerebellar degeneration (PCD) treated with autologous hematopoietic stem cell transplantation (AHSCT).</p><p><strong>Methods: </strong>Off-label AHSCT was performed at Hospital Clinic Barcelona, including stem cell mobilization (cyclophosphamide, filgrastim), plasma exchange, and a nonmyeloablative regimen (cyclophosphamide, antithymocyte globulin, rituximab [RTX]).</p><p><strong>Results: </strong>A 38-year-old woman developed anti-Yo-associated PCD 17 months after treatment of a gynecologic cancer (without evidence of tumor recurrence). Despite treatment with steroids and RTX, she became unable to walk. AHSCT resulted in progressive improvement, no longer needing assistance to walk 9 months after AHSCT. Tumor recurrence, without neurologic worsening, was identified 16 months after AHSCT, and chemotherapy was restarted. At the last follow-up (46 months), she continues on chemotherapy without neurologic deterioration. A 48-year-old man developed PCD associated with Tr/delta/notch-like epidermal growth factor-related receptor antibodies. Axillary lymph node biopsy demonstrated Hodgkin lymphoma. Chemoradiation resulted in complete tumor response, but cerebellar ataxia worsened despite treatment with steroids and IV immunoglobulins. Ten months after cerebellar symptom onset, he underwent AHSCT resulting in neurologic improvement. At the last follow-up, 39 months after AHSCT, he remains independent in activities of daily living.</p><p><strong>Discussion: </strong>In our experience, AHSCT is worth to be considered in patients with progressive PCD refractory to conventional oncological and immunotherapy treatments.</p><p><strong>Classification of evidence: </strong>This is a single observational study without controls and provides Class IV evidence.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"12 5","pages":"e200433"},"PeriodicalIF":7.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12270494/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144650034","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":"KFLC to Total CSF Protein Ratio Is an Alternative to KFLC Index to Diagnose Multiple Sclerosis: A Retrospective Study of 814 Cases.","authors":"Estelle Moschetti, Mélany Venet, Lise Thibaudin, Amelie Moreau, Philippe Gonzalo, Jean-Philippe Camdessanche, Yannick Tholance","doi":"10.1212/NXI.0000000000200451","DOIUrl":"10.1212/NXI.0000000000200451","url":null,"abstract":"<p><strong>Background and objectives: </strong>Biological analyses are crucial for diagnosing multiple sclerosis (MS), notably detection of oligoclonal bands (OCBs) of immunoglobulin G in CSF. Kappa free light chain (KFLC) quantification in serum and CSF has recently been proposed as an additional test. In a rational medicoeconomic approach, identifying algorithms or biomarkers is important. The objective of this study was, therefore, to evaluate the correlation between CSF kappa free light chain (KFLC_CSF)/total CSF protein ratio (KFLC_CSF/Prot_CSF) and OCB status and its performance in diagnosing MS.</p><p><strong>Methods: </strong>KFLC measurements were performed prospectively with each OCB analysis, and the data were interpreted retrospectively. A total of 814 clinical cases were included: 153 with MS or clinically isolated syndrome (CIS), 181 with other inflammatory neurologic diseases, and 480 with noninflammatory neurologic diseases. Performances of KFLC_CSF/Prot_CSF in predicting OCB status, diagnosing MS, and estimating evolution of CIS to MS were evaluated and compared with those of other KFLC parameters, i.e., KFLC index, and with OCB and IgG parameters.</p><p><strong>Results: </strong>KFLC_CSF/Prot_CSF and KFLC index performed similarly in predicting OCB status, with a sensitivity of 80.2% and a specificity of 93.4% at a threshold >0.21% for KFLC_CSF/Prot_CSF (area under the curve: 0.93). The percentage of agreement between OCB status and KFLC_CSF/Prot_CSF was 91.2%. Using KFLC_CSF and KFLC_CSF/Prot_CSF initially could reduce OCB testing by 68% and quantitative tests by 48.4%. For diagnosing MS/CIS, KFLC_CSF/Prot_CSF performed similar to or slightly worse than the KFLC index but always outperformed IgG, OCB, and KFLC_CSF. For this indication, the optimal threshold for KFLC_CSF/Prot_CSF was >0.24%. It is important to note that KFLC_CSF/Prot_CSF was the most predictive parameter for CIS progression to MS.</p><p><strong>Discussion: </strong>To conclude, KFLC_CSF/Prot_CSF is as an easier and cost-effective alternative for predicting OCB status and CIS progression to MS and assisting in the diagnosis of MS.</p><p><strong>Classification of evidence: </strong>This study provides Class II evidence that the KFLC_CSF/Protein_CSF ratio accurately distinguishes patients with CSF OCBs from those without CSF OCBs and patients with MS from those with other neurologic disorders.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"12 5","pages":"e200451"},"PeriodicalIF":7.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12285672/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144691134","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":"Serum Autoantibody Titers and Neurofilament Light Chain Levels in CASPR2/LGI1 Encephalitis: A Longitudinal Study.","authors":"Pietro Businaro, Stefano Masciocchi, Ruggero Barnabei, Silvia Scaranzin, Chiara Morandi, Matteo Scucchi, Sara Bernini, Sara Bottiroli, Paolo Barone, Antonella Toriello, Carla Arbasino, Chiara Padiglioni, Silvia Cenciarelli, Luana Benedetti, Denise Cerne, Mario Risi, Matteo Paoletti, Anna Pichiecchio, Luca Diamanti, Paola Bini, Elisabetta Zardini, Diego Franciotta, Matteo Gastaldi","doi":"10.1212/NXI.0000000000200431","DOIUrl":"10.1212/NXI.0000000000200431","url":null,"abstract":"<p><strong>Background and objectives: </strong>Autoantibodies against contactin-associated protein-like 2 (CASPR2-IgG) and leucine-rich glioma inactivated 1 protein (LGI1-IgG) identify a subgroup of autoimmune encephalitis (AE). Up to 65% of patients with LGI1/CASPR2 AE show cognitive sequelae that are unpredictable at onset. We aimed to assess the clinical relevance of serum autoantibody titers and neurofilament light chain (NfL) levels as biomarkers in CASPR2/LGI1 AE.</p><p><strong>Methods: </strong>We selected consecutive CASPR2/LGI1-IgG-positive patients with at least 2 longitudinal serum samples obtained more than 60 days apart. Samples were defined as acute (first diagnostic evaluation after onset or relapse and before immunotherapy) and remission (>2 months from attack). CASPR2/LGI1-IgG was titered with a live cell-based assay. Functional outcome was measured using modified Rankin Scale and Clinical Assessment Scale in AE and cognitive impairment using Montreal Cognitive Assessment (MoCA).</p><p><strong>Results: </strong>We included 23 patients (LGI1 = 15, CASPR2 = 7, CASPR2/LGI1 = 1) with 130 serum samples (acute = 32; remission = 98). Serum titers in the acute phase were higher than in remission and decreased over time and after immunosuppressive treatment. In 9 of 10 patients, relapses occurred with seropositive samples, and in 4 of 5 patients, these occurred with increased titers. Onset titers did not correlate with functional/cognitive outcome at follow-up.Serum NfL median levels in both patients with LGI1 AE (35.3 pg/mL, range: 5.4-164) and CASPR2 AE (31.4 pg/mL, range: 9.11-120) were higher than in age/sex-matched controls (14.55, range: 5.4-56.8, <i>p</i> = 0.004 and <i>p</i> < 0.001, respectively). Acute-phase samples had higher NfL median levels (47.2, range: 9.11-120) compared with remission (31.2 pg/mL; range, 5.4-114, <i>p</i> = 0.02). NfL levels at onset predicted lower MoCA scores at follow-up in univariate linear regression analysis (B = -3.881, <i>p</i> = 0.0256). NfL levels decreased over time, but at the last follow-up remained higher than those in controls (<i>p</i> = 0.02).</p><p><strong>Discussion: </strong>Measuring LGI1 and CASPR2-IgG titers in AE could help to confirm the disease stage and define relapses but has no prognostic implications. Serum NfL at onset could be used to identify patients at higher risk of cognitive sequelae that might deserve tailored management.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"12 5","pages":"e200431"},"PeriodicalIF":7.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12202019/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144497570","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":"Progression Independent of the Triggering Event in Neurologic Diseases.","authors":"Howard L Weiner","doi":"10.1212/NXI.0000000000200447","DOIUrl":"10.1212/NXI.0000000000200447","url":null,"abstract":"","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"12 5","pages":"e200447"},"PeriodicalIF":7.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12270492/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144650036","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":"Peripheral HLA-DR^hiCD141⁺ Classical Monocytes Predict Relapse Risk and Worsening in Multiple Sclerosis.","authors":"Karine Thai, Rose-Marie Rebillard, Wendy Klement, Othmane Ayoub, Olivier Tastet, Skander Ben Ahmed, Bettina Zierfuss, Camille Grasmuck, Fiona Tea, Lyne Bourbonniere, Clara Margarido, Chloé Juliette Hoornaert, Francis Carrier, Elizabeth Gowing, Mathieu Dubé, Stephanie Zandee, Marc Girard, Pierre Duquette, Boaz Lahav, Nathalie Arbour, Catherine Larochelle, Alexandre Prat","doi":"10.1212/NXI.0000000000200426","DOIUrl":"10.1212/NXI.0000000000200426","url":null,"abstract":"<p><strong>Background and objectives: </strong>Multiple sclerosis (MS) is an immune-mediated demyelinating disease of the CNS characterized by a heterogeneous disease trajectory, highlighting the need for biomarkers to predict disease activity. Current disease-monitoring tools primarily reflect existing disease damage rather than impending activity. Peripheral blood mononuclear cells (PBMCs) are an ideal source of potential biomarkers due to their accessibility and their known role in MS pathology. Among PBMCs, myeloid cells are key players in MS pathogenic processes, yet they have not been as extensively studied than lymphocytes. The objective of our study was to identify indicators of MS disease activity through immune profiling.</p><p><strong>Methods: </strong>We analyzed PBMCs using high-dimensional flow cytometry with a panel focusing on myeloid cells. We performed unsupervised clustering analyses to define a comprehensive immune landscape at a single-cell resolution. Supervised machine learning methods were used to extract immune features indicative of MS activity.</p><p><strong>Results: </strong>We analyzed PBMCs from 135 individuals with MS with retrospective longitudinal follow-up and 44 healthy controls (HCs). Among the individuals with MS, 53 were untreated and were compared with HCs. Using an elastic-net model, 20 immune features were identified as contributors to the classification of MS and HCs (receiver operating characteristic-AUC 0.8881). To explore associations between immune features and disease activity, we focused on individuals with relapsing-remitting MS (n = 106). We identified a subpopulation of classical monocytes (CMs) with high expression of human leukocyte antigen - DR isotype (HLA-DR) and positive for CD141 (HLA-DR^hiCD141⁺) as a predictor of impending relapses over 2 years (hazard ratio [HR] 2.8, 95% CI 1.6-4.7) and disability worsening in patients with higher relapse activity. HLA-DR^hiCD141⁺ CMs could be retrieved by manual gating using 9 parameters and were similarly indicative of 2-year relapse risk (HR 1.9, 95% CI 1.3-2.8), highlighting its potential as a practical, translational approach. Compared with the widely studied biomarker serum neurofilament light chain reflecting acute activity, HLA-DR^hiCD141⁺ CMs provided a stronger prognostic value for impending relapse risk, suggesting different kinetics related to the underlying pathology.</p><p><strong>Discussion: </strong>Our findings suggest that the frequency of HLA-DR^hiCD141⁺ CMs could serve as a valuable predictor of disease activity complementary to current clinical tools to guide evidence-based treatment decisions.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"12 5","pages":"e200426"},"PeriodicalIF":7.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12227149/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144560688","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":"Pregnancy and Infant Outcomes in Multiple Sclerosis: Findings From the Global MAPLE-MS Pharmacovigilance Program.","authors":"Kerstin Hellwig, Hugh H Tilson, Sandra Thiel, Kathryn Ball, Joerg Seebeck, Muriel Danten, Nancy Dubois, Meritxell Sabidó","doi":"10.1212/NXI.0000000000200438","DOIUrl":"10.1212/NXI.0000000000200438","url":null,"abstract":"<p><strong>Background and objectives: </strong>With its use being contradicted during pregnancy, limited information exists concerning pregnancy and infant outcomes on exposure to cladribine tablets before or during pregnancy in women with multiple sclerosis (MS). In this study, we assess cumulative pregnancy exposure to cladribine tablets and prevalence of pregnancy and infant outcomes in women with MS exposed during pregnancy or within 6 months before conception and pregnancies fathered by men with MS exposed within 6 months before conception.</p><p><strong>Methods: </strong>MAPLE-MS, a 10-year enhanced pharmacovigilance program, uses a global patient safety database to assess pregnancy outcomes potentially associated with cladribine tablets exposure in MS. Data collection began after the first approval of cladribine tablets (August 22, 2017). The primary outcome is the prevalence of major congenital anomalies (MCAs) in offspring. Secondary outcomes include other pregnancy outcomes (live birth, elective termination, spontaneous abortion, ectopic pregnancy, and stillbirth).</p><p><strong>Results: </strong>In this Year 7 interim analysis, of 383 pregnancies analyzed, 336 (87.7%) involved maternal exposure to cladribine tablets and 47 (12.3%) were associated with paternal exposure. In the maternal exposure group, MCA prevalence (excluding genetic anomalies) in pregnancies with known outcomes was 1.1% (95% confidence interval [CI] 0.0-6.7; an atrial septal defect). Prevalence of live births in the maternal exposure group was 57.3% (95% CI 49.5-64.8). Secondary outcomes in the maternal exposure group were elective terminations (21.0% [95% CI 15.3-28.1]), spontaneous abortions (20.4% [95% CI 14.8-27.4]), and ectopic pregnancies (1.3% [95% CI 0.1-4.8]). In the paternal exposure group, no cases of MCA were observed in live births with known outcomes. Prevalence of live births was 81.3% (95% CI 56.2-94.2). Spontaneous abortions occurred in 12.5% (95% CI 2.2-37.3) and stillbirths in 6.3% (95% CI 0.0-30.3) of cases.</p><p><strong>Discussion: </strong>Results are limited by the small number of pregnancies with known outcomes. Of pregnancies with known outcomes, the majority resulted in live births, with low frequencies of elective terminations and stillbirths reported. Since 2017, a single MCA (atrial septal defect) has been reported to the global patients' safety database. The results align with published estimates from the general population and MS patient cohorts.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"12 5","pages":"e200438"},"PeriodicalIF":7.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12221160/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144529042","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 Marker Changes Associated With Disease Activity in Relapsing-Remitting Multiple Sclerosis.","authors":"Victoria Lim Falk, Nicole Mueller-Wirth, Dimitris Karathanasis, Maria Eleftheria Evangelopoulos, Aleksandra Maleska Maceski, Amar Zadic, Jens Kuhle, Cornelia Schlup, Stefanie Marti, Kirsten Guse, Andrew Chan, Vincent Pernet","doi":"10.1212/NXI.0000000000200404","DOIUrl":"https://doi.org/10.1212/NXI.0000000000200404","url":null,"abstract":"<p><strong>Background and objectives: </strong>Multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) are autoimmune disorders of the CNS causing severe neurologic impairment. Evidence suggests that extracellular vesicles (EVs) may play a disease-specific role in the orchestration of the immune cell response of MS, NMOSD, and MOGAD. In addition, EVs are considered as a potential source of biomarkers that may allow us to establish molecular signatures for these diseases and perhaps as well to follow treatment effects and disease progression. The aim of this study was to analyze the composition of EVs in patients with relapsing-remitting MS (RRMS) (n = 52), NMOSD (n = 19), and MOGAD (n = 10) and healthy controls ([HCs], n = 15).</p><p><strong>Methods: </strong>The concentrations of neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) were determined in plasma using single-molecule array (SIMOA). The size and concentration of tetraspanin-presenting EVs were evaluated in plasma samples with a single-particle interferometric resonance imaging sensor (SP-IRIS). Tetraspanin-independent analyses were performed by nanoparticle-tracking analysis (NTA) after EV isolation by size exclusion (SmartSEC) and cryo-electron microscopy observations. EV epitopes were analyzed by extended multiplex analysis using flow cytometry.</p><p><strong>Results: </strong>The plasma concentration of NfL and GFAP was significantly higher in patients with RRMS than in HCs. For patients with NMOSD, only GFAP increased. The density of EVs assessed by NTA was lower in plasma of patients with RRMS than in HC plasma. In addition, the 3 disease groups presented increased mean EV sizes in comparison with HCs. Tetraspanin-based EV analyses by SP-IRIS allowed us to observe a modest difference in the level of CD81 in RRMS EVs. In patients with RRMS, but not in those with NMOSD and MOGAD, multiplex/flow cytometry analyses revealed changes in the EV levels of CD29, CD31, and CD69 associated with the time elapsed since the last relapse. The negative correlations established between the vesicular levels of CD31, CD40, CD44, CD49c, CD69, and NfL or GFAP z-scores suggest a negative relationship specifically in RRMS.</p><p><strong>Discussion: </strong>We speculate that the higher release of EVs containing CD29, CD31, CD40, CD44, CD49c, and CD69 in plasma, at low levels of circulating NfL/GFAP, may be associated with reduced immune cell activity in RRMS. These EV markers may characterize patients with RRMS in disease stabilization.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"12 4","pages":"e200404"},"PeriodicalIF":7.8,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12056760/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144032750","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":"Glymphatic System May Mediate the Relation Between Choroid Plexus and Brain Damage in Multiple Sclerosis.","authors":"Paolo Preziosa, Elisabetta Pagani, Monica Margoni, Martina Rubin, Loredana Storelli, Gianluca Corazzolla, Maria A Rocca, Massimo Filippi","doi":"10.1212/NXI.0000000000200414","DOIUrl":"10.1212/NXI.0000000000200414","url":null,"abstract":"<p><strong>Background and objectives: </strong>The choroid plexus (CP) regulates immune functions and produces most CSF that circulates in the brain parenchyma through perivascular spaces, part of the glymphatic system. In multiple sclerosis (MS), CP enlargement and glymphatic dysfunction are associated with inflammatory activity, clinical disability, and brain damage, but their interrelation is unclear. We investigated whether glymphatic system dysfunction mediates the association between CP enlargement and brain damage in patients with MS.</p><p><strong>Methods: </strong>Brain fluid-attenuated inversion recovery, 3-dimensional T1-weighted, diffusion-weighted, and susceptibility-weighted sequences were obtained from 146 patients with MS and 72 healthy controls (HC). Glymphatic function was assessed using the diffusion along the perivascular space (DTI-ALPS) index, and CP volume was measured automatically.</p><p><strong>Results: </strong>Patients with MS showed significantly higher white matter (WM) lesion and CP volumes (<i>p</i> < 0.001), and lower DTI-ALPS index, brain, WM, thalamic, and cortical volumes than HC (<i>p</i> ≤ 0.048). In patients with MS, higher CP volume correlated with a lower DTI-ALPS index (<i>r</i> = -0.305, false discovery rate p value = 0.001). Both measures were associated with higher total, periventricular, and juxtacortical (JC) WM lesion volumes (CP volume: <i>r</i> from 0.285 to 0.340, p-FDR ≤ 0.001; DTI-ALPS index: <i>r</i> from -0.301 to -0.444, <i>p</i> ≤ 0.001), and lower brain, thalamic, cortical, and WM volumes (CP volume: <i>r</i> from -0.246 to -0.405, p-FDR ≤ 0.006; DTI-ALPS index: from 0.269 to 0.497, p-FDR ≤ 0.003). The DTI-ALPS index partially mediated the associations of normalized choroid plexus volume with total, periventricular, and JC T2-hyperintense WM lesion volumes (standardized-β ranging from 0.073 to 0.115, relative effect ranging from 25.2% to 33.6%) and normalized brain, thalamic, cortical, and WM volumes (standardized-β ranging from -0.086 to -0.125, relative effect ranging from 25.3% to 52.7%).</p><p><strong>Discussion: </strong>In MS, enlarged normalized CP volume may contribute to brain damage accumulation possibly through the promotion of a chronic proinflammatory state and the mediation of glymphatic system dysfunction.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"12 4","pages":"e200414"},"PeriodicalIF":7.8,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12153948/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144234682","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":"Acute and Long-Term Immune-Treatment Strategies in Anti-LGI1 Antibody-Mediated Encephalitis: A Multicenter Cohort Study.","authors":"Nabil Seery, Robb Wesselingh, Paul Beech, Laurie M 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 J Duncan, Wendyl Jude D'Souza, Yang David 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 William Reddel, Todd A Hardy, Terence J O'Brien, Paul G Sanfilippo, Helmut Butzkueven, Mastura Monif","doi":"10.1212/NXI.0000000000200412","DOIUrl":"10.1212/NXI.0000000000200412","url":null,"abstract":"<p><strong>Background and objectives: </strong>Few studies have evaluated acute immunotherapy and relapse prevention strategies in patients with anti-leucine-rich glioma-inactivated 1 (LGI1) antibody (Ab)-mediated encephalitis. The objective of this study was to analyze the outcomes of acute and long-term immunotherapy strategies in this population.</p><p><strong>Methods: </strong>We undertook a multicenter cohort study of 55 patients with anti-LGI1 Ab-mediated encephalitis, either recruited prospectively or identified retrospectively from 10 Australian hospitals as part of the Australian Autoimmune Encephalitis Consortium. Clinical data were collected, including treatment durations of all relevant immunotherapies. Clinical outcomes that we examined included (1) time to first clinical relapse, (2) improvement on modified Rankin Scale (mRS), and (3) favorable binary composite clinical-functional outcome at 12 months. A favorable outcome was defined as fulfilling all three of mRS less than 3, a score of 1 or less in the memory dysfunction component of the Clinical Assessment Scale in Autoimmune Encephalitis, and absence of drug-resistant epilepsy.</p><p><strong>Results: </strong>Rituximab, adjusted for concomitant use of other immunotherapies, was associated with increased time to first relapse (hazard ratio 0.10; 95% CI 0.001-0.85; <i>p</i> = 0.03). Intravenous pulsed methylprednisolone was associated with an improvement in mRS (OR 4.48; 95% CI 1.03-21.3; <i>p</i> = 0.048) and a favorable composite clinical-functional outcome (OR 4.96; 95% CI 1.07-27.2; <i>p</i> = 0.049) at 12 months.</p><p><strong>Discussion: </strong>Rituximab may be effective at preventing relapses in patients with anti-LGI1 Ab-mediated encephalitis. Acute methylprednisolone treatment may be associated with favorable outcomes at 12 months.</p><p><strong>Classification of evidence: </strong>This study provides Class IV evidence that for patients with anti-LGI1 Ab-mediated encephalitis, rituximab prevents relapses and acute methylprednisolone is associated with favorable outcomes at 12 months.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"12 4","pages":"e200412"},"PeriodicalIF":7.8,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12185223/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144333577","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}