Neurology® Neuroimmunology & Neuroinflammation最新文献

{"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":"Serum Neurofilament Light Chain as a Biomarker for CIDP Diagnosis, Severity, and Treatment Outcome.","authors":"Rafael Klimas, Felix Kohle, Lea Horstkemper, Pascal Benkert, Adriana Rehm, Aylin Seibert, Moritz Riesner, Melissa Sgodzai, Thomas Grüter, Niklas Rilke, Barbara Gisevius, Léon Beyer, Klaus Gerwert, Jens Kuhle, Michael Schroeter, Helmar C Lehmann, Ralf Gold, Anna Lena Fisse, Jeremias Motte, Kalliopi Pitarokoili","doi":"10.1212/NXI.0000000000200419","DOIUrl":"10.1212/NXI.0000000000200419","url":null,"abstract":"<p><strong>Background and objectives: </strong>The aim of this study was to characterize serum neurofilament light chain (sNFL) levels in a large cohort of patients with autoimmune neuropathies to provide every-day clinical practice recommendations.</p><p><strong>Methods: </strong>In this retrospective cohort study, we recruited 191 patients with immune-mediated neuropathies from 2 referral centers. sNFL was measured using the Simoa NF-light kit (Quanterix), and age-corrected and BMI-corrected z-scores (zNFL) were calculated. Clinical data were correlated with zNFL and adjusted for different disease subsets. A receiver operator characteristic analysis was performed. Treatments and longitudinal disease course of patients with typical chronic inflammatory demyelinating polyneuropathy (CIDP) in early disease stage were analyzed.</p><p><strong>Results: </strong>One hundred ten patients had typical CIDP, and 67 had atypical CIDP. Fourteen patients had other immune neuropathies. zNFL of all patients correlated significantly with the Inflammatory Neuropathy Cause and Treatment Scale-overall disability sum score (<i>r</i> = 0.160), Medical Research Council Scale for Muscle Strength score (<i>r</i> = -0.242), modified Rankin Scale score (<i>r</i> = 0.151), and distal tibial compound muscle action potential (<i>r</i> = -0.151). The correlations remained only in the cohort of typical CIDP. zNFL >2 within the first 24 months of illness differentiated patients with atypical and typical CIDP with a sensitivity of 93%. Patients with early-stage typical CIDP with zNFL >2 (n = 9) presented with the most severe manifestation and did not respond to first-line (<i>p</i> < 0.0001) but to second-line treatments.</p><p><strong>Discussion: </strong>We established sNFL as a promising biomarker for assessing disease activity in patients with typical CIDP. Elevated zNFL in early-stage typical CIDP indicate severe inflammatory-mediated axonal damage that requires aggressive immunotherapy.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"12 4","pages":"e200419"},"PeriodicalIF":7.8,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12153944/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144234683","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":"The Italian Multiple Sclerosis Register Experience With Cladribine: Impact on Relapses, PIRA, and Treatment Sequencing Strategies Evaluation.","authors":"Tommaso Guerra, Massimiliano Copetti, Chiara Zanetta, Francesco Patti, Clara Grazia Chisari, Elena Barbuti, Emilio Portaccio, Matteo Foschi, Antonella Conte, Diana Ferraro, Eleonora E Cocco, Roberta Fantozzi, Giorgia Teresa Maniscalco, Giuseppe Salemi, Carla Tortorella, Damiano Paolicelli, Massimo Filippi, Maria Pia Amato, Maria Trojano, Pietro Iaffaldano","doi":"10.1212/NXI.0000000000200415","DOIUrl":"10.1212/NXI.0000000000200415","url":null,"abstract":"<p><strong>Background and objectives: </strong>Cladribine is an immune reconstitution therapy approved for relapsing multiple sclerosis (RMS). This multicentric retrospective study of the Italian Multiple Sclerosis Register (RISM) aimed to assess the effect of cladribine on the annualized relapse rate (ARR) and progression independent of relapse activity (PIRA) phenomena, also evaluating the strategies of disease-modifying treatment (DMT) continuation after cladribine termination.</p><p><strong>Methods: </strong>Patients with RMS treated with at least one cycle of cladribine recorded in RISM after 2018 were retrospectively included in the analysis. Patients previously treated with other DMTs were stratified into moderately and highly effective DMTs. Adjusted ARR and PIRA events were calculated in the overall cohort and stratified by age at cladribine start (<50 vs ≥ 50 years) and by previous DMT. ARRs were compared between groups using negative binomial models. PIRA was analyzed using the Ghosh-Lin Cox-type regression for the marginal mean. DMTs prescribed after cladribine cycles were analyzed.</p><p><strong>Results: </strong>A total of 2,329 patients treated with cladribine were identified in RISM, with a median (IQR) age of 36.5 (29.2-45.2) years at treatment start. 1,488 patients (63.9%) received 2 courses of cladribine. ARR decreased (<i>p</i> < 0.0001) from 0.96 (95% CI 0.91-1.02) in the 2 years preceding cladribine start to 0.09 (0.08-0.11) during the 2 years after in the overall cohort. One hundred thirty-three PIRA events were reported during the noncladribine treatment period and 54 during cladribine therapy (HR 0.711, 95% CI 0.531-0.952, <i>p</i> = 0.0219) in the entire cohort. All the analyses stratified by age and previous treatment confirmed the significant reduction in PIRA events and the suppression of relapse activity. After cladribine, most DMTs prescribed were ocrelizumab, ofatumumab, and natalizumab. Eight patients re-treated with an additional cycle of cladribine were also identified.</p><p><strong>Discussion: </strong>For patients with RMS, both naïve and switchers, as well as younger and older patients, cladribine is an effective treatment in reducing relapses and PIRA. Different therapeutic strategies after cladribine are currently reported.</p><p><strong>Classification of evidence: </strong>This study provides Class IV evidence that for patients with relapsing multiple sclerosis, cladribine treatment is associated with a reduction in ARR and PIRA events.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"12 4","pages":"e200415"},"PeriodicalIF":7.8,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12153946/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144234684","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":7.5,"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}

{"title":"Acknowledgment to Reviewers.","authors":"Scott S Zamvil, Anne-Katrin Proebstel, Marinos C Dalakas, Josep O Dalmau, Romana Höftberger, Dennis L Kolson","doi":"10.1212/NXI.0000000000200441","DOIUrl":"10.1212/NXI.0000000000200441","url":null,"abstract":"","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"12 4","pages":"e200441"},"PeriodicalIF":7.8,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12153940/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144234681","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":"The Inner Nuclear Layer in Pediatric Multiple Sclerosis.","authors":"Hannah Hummel-Abmeier, Sabine Naxer, Ella Maria Kadas, Hanna Zimmermann, Bianca Knaack, Peter Huppke, Antonia Kowallick, Kolja Meier, Alexander Ulrich Brandt, Friedemann Paul, Michael Schittkowski, Frederike Cosima Oertel, Jutta Gärtner","doi":"10.1212/NXI.0000000000200424","DOIUrl":"10.1212/NXI.0000000000200424","url":null,"abstract":"","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"12 4","pages":"e200424"},"PeriodicalIF":7.8,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12065112/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143972159","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":"Identification of Distinct Biological Groups of Patients With Cryptogenic NORSE via Inflammatory Profiling.","authors":"Martin Guillemaud, Mario Chavez, Firas Kobeissy, Annamaria Vezzani, Anthony D Jimenez, Maysaa Merhi Basha, Ayush Batra, Sophie Demeret, Onome Eka, Krista Eschbach, Brandon Foreman, Nicolas Gaspard, Elizabeth E Gerard, Teneille Emma Gofton, Hiba A Haider, Stephen T Hantus, Charles L Howe, Amy Jongeling, Mariel Kalkach-Aparicio, Padmaja Kandula, Karnig Kazazian, Minjee Kim, Yi-Chen Lai, Clémence Marois, Andrew Mellor, Wazim Mohamed, Mikaela Morales, Cederic M Pimentel, Alexandra M Ramirez, Claude Steriade, Aaron F Struck, Olga Taraschenko, Nathan Torcida Sedano, Mark S Wainwright, Ji Yeoun Yoo, Kevin K W Wang, Vincent Navarro, Lawrence J Hirsch, Aurélie Hanin","doi":"10.1212/NXI.0000000000200403","DOIUrl":"10.1212/NXI.0000000000200403","url":null,"abstract":"<p><strong>Background and objectives: </strong>Emerging evidence suggests that immune dysregulation plays a pivotal role in triggering cryptogenic new-onset refractory status epilepticus (c-NORSE), prompting a consensus on early initiation of immunotherapy. However, despite similar timing of administration, responses to immunotherapies have been varied and unpredictable, suggesting the presence of heterogeneous underlying mechanisms<b>.</b> The aim of this study was to identify distinct inflammatory response subtypes in patients with c-NORSE by analyzing their cytokine profiles. Insights into underlying mechanisms were sought to understand the pathophysiology and guide personalized therapies to improve patient outcomes.</p><p><strong>Methods: </strong>Sixty-two patients with c-NORSE were included. A comprehensive panel of 96 cytokines was analyzed in serum samples. Patients were clustered based on their cytokine profiles using the Louvain algorithm, an unsupervised graph-based clustering method. The identified clusters of patients were compared regarding cytokine levels and clinical features. Protein pathway analysis was used to explore the biological relevance of the inflammatory markers within each cluster. Patients with c-NORSE were compared with control patients (n = 18) and patients with other forms of refractory SE (n = 45).</p><p><strong>Results: </strong>Compared with controls, patients with c-NORSE exhibited significant differences in 33 cytokines. Pathway analysis revealed dysregulations in chemotaxis and neutrophil recruitment and migration, highlighting the importance of innate immunity in patients with c-NORSE. Within the c-NORSE cohort, 3 clusters of patients emerged: cluster A, lacking specific inflammatory markers; cluster B, with a much stronger innate-immunity cytokine-driven inflammatory response compared with clusters A and C; and cluster C, defined by dysregulated autoimmune processes. Notably, patients in cluster B showed a statistically significant elevation of innate immune-related proinflammatory cytokines associated with leukocyte recruitment and degranulation. By contrast, those in cluster C showed activation of Janus kinase signal transducer and activator of transcription (JAK-STAT) pathways, suggesting autoimmune mechanisms. Patients in clusters B and C demonstrated varied responses to immunotherapies, with cluster C patients showing favorable outcomes after multiple immunotherapies.</p><p><strong>Discussion: </strong>The identification of distinct inflammatory subgroups in c-NORSE suggests that variations in the underlying immune mechanisms contribute to differential treatment responses. These findings underscore the importance of personalized therapeutic strategies, potentially targeting specific inflammatory pathways, to optimize clinical outcomes in this challenging condition.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"12 4","pages":"e200403"},"PeriodicalIF":7.8,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12063244/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144010110","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":"Intrathecal Inflammatory Profile and Gray Matter Damage Predict Progression Independent of Relapse Activity in Early Multiple Sclerosis.","authors":"Damiano Marastoni, Elisa Colato, Matteo Foschi, Agnese Tamanti, Stefano Ziccardi, Chiara Eccher, Francesco Crescenzo, Albulena Bajrami, Gian Marco Schiavi, Valentina Camera, Daniela Anni, Federica Virla, Maddalena Guandalini, Ermanna Turano, Francesca Benedetta Pizzini, Stefania Montemezzi, Bruno Bonetti, Owain Howell, Roberta Magliozzi, Richard S Nicholas, Antonio Scalfari, Cristina Granziera, Ludwig Kappos, Massimiliano Calabrese","doi":"10.1212/NXI.0000000000200399","DOIUrl":"https://doi.org/10.1212/NXI.0000000000200399","url":null,"abstract":"<p><strong>Background and objectives: </strong>The objective of this study was to determine, at the time of diagnosis, a CSF and MRI profile of intrathecal compartmentalized inflammation predictive of progression independent of relapse activity (PIRA) in early relapsing-remitting multiple sclerosis (RRMS).</p><p><strong>Methods: </strong>This five-year prospective study included 80 treatment-naïve patients with RRMS enrolled at time of diagnosis. All patients underwent a lumbar puncture, regular neurologic evaluations including an Expanded Disability Status Scale (EDSS) assessment every 6 months, and an annual 3T brain MRI. PIRA was defined as having a confirmed disability progression independent of relapse activity. CSF levels of 68 inflammatory molecules were evaluated in combination with white matter and cortical lesion number (CLn) and volume, and regional gray matter thickness and volume.</p><p><strong>Results: </strong>During the follow-up, 23 patients with RRMS (28.8%) experienced PIRA. At diagnosis, participants with PIRA were older (44.0 ± 10.7 vs 37.4 ± 12.4, <i>p</i> = 0.017) and with more disability (median EDSS score [interquartile range] of 3 [range 2-4] for PIRA vs 1.5 [range 1-2] for no PIRA group, <i>p</i> < 0.001). Random forest selected LIGHT, CXCL13, sTNFR1, sTNFR2, CCL7, MIF, sIL6Rbeta, IL35, CCL2, and IFNβ as the CSF markers best associated with PIRA. sTNFR1 (hazard ratio [HR] 10.11 [2.61-39.10], <i>p</i> = 0.001), sTNFR2 (HR 5.05 [1.63-15.64], <i>p</i> = 0.005), and LIGHT (HR 1.79 [1.11-2.88], <i>p</i> = 0.018) were predictors of PIRA at regression analysis. Baseline thalamus volume (HR 0.98 [0.97-0.99], <i>p</i> = 0.005), middle frontal gyrus thickness (HR 0.05 [0.01-0.72], <i>p</i> = 0.028), and CLn (HR 1.15 [1.05-1.25], <i>p</i> = 0.003) were MRI predictors of PIRA.</p><p><strong>Discussion: </strong>A specific intrathecal inflammatory profile associated with TNF superfamily markers, CLn, and atrophy of several cortical and deep gray matter regions, assessed at time of diagnosis, is predictive of PIRA in early MS.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"12 4","pages":"e200399"},"PeriodicalIF":7.8,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12056761/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144030495","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 (II): Antibodies to Surface Antigens.","authors":"Claudia Papi, Chiara Milano, Lionel Arlettaz, Pietro Businaro, Laura Marmolejo, Laura Naranjo, Jesús Planagumà, Eugenia Martinez-Hernandez, Thaís Armangué, Mar Guasp, Raquel Ruiz-García, Esther Aguilar, Matteo Gastaldi, Raffaele Iorio, Carles Gaig, Albert Saiz, Lidia Sabater, Francesc Graus, Josep O Dalmau, Marianna Spatola","doi":"10.1212/NXI.0000000000200406","DOIUrl":"10.1212/NXI.0000000000200406","url":null,"abstract":"<p><strong>Background and objectives: </strong>Detecting neural surface antibodies (NSAbs) is essential for diagnosing autoimmune encephalitis. The recommended diagnostic strategy involves initial screening with tissue-based assays (TBAs), followed by confirmation with cell-based assays (CBAs). While specialized centers use in-house TBAs, many clinical laboratories depend on commercial TBAs, whose accuracy is yet to be fully assessed.</p><p><strong>Methods: </strong>We selected 92 CSF and 99 serum samples from patients with autoimmune encephalitis and NSAbs confirmed by in-house TBAs and CBAs (20 samples each for AMPAR, GABA_AR, GABA_BR, IgLON5, LGI1, NMDAR, and CASPR2; 19 for mGluR5; 17 for DPPX; and 15 for mGluR1 antibodies), along with 50 CSF and 50 serum samples from negative controls. We assessed the performance of a commercial indirect immunofluorescence (IIF)-TBA (EUROIMMUN). Slides were evaluated as \"positive\" or \"negative\" by 2 experienced investigators and 2 less experienced raters. Discordant results were re-evaluated through interrater discussion and assessed using Cohen's kappa.</p><p><strong>Results: </strong>The experienced raters agreed on 94% (133/142) of CSF and 88% (131/149) of serum classifications (Cohen's kappa = 0.87 and 0.75, respectively, <i>p</i> < 0.001). Among CSF samples, 75% (106/142) were correctly identified while 19% (27/142) were misclassified (13 false positives, 14 false negatives). Among serum samples, 66% (98/149) were correctly identified while 22% (33/149) were misclassified (11 false positives, 22 false negatives). The poorest performance was seen in detecting NMDAR, GABA_AR, and mGluR5 Abs, which were not identified in 5 of 10, 6 of 10, and 5 of 9 serum samples and in 4 of 10, 5 of 10, and 5 of 10 CSF samples, respectively. The overall sensitivity of the commercial IIF-TBA was 84% for CSF and 76% for serum while the specificity was 72% for CSF and 73% for serum. Less experienced raters correctly identified 69% (98/142) of CSF samples and 73% (109/149) of serum samples and misclassified 13% (18/142) of CSF samples and 11% (16/149) of serum samples, and 18% (26/142) of CSF samples and 16% (24/149) of serum samples remained discordant.</p><p><strong>Discussion: </strong>The diagnostic performance of EUROIMMUN IIF-TBA in detecting NSAbs in autoimmune encephalitis is suboptimal. NMDAR antibodies, among the most common NSAbs, can be missed in 50% of cases. This commercial TBA should not be used alone as a screening method nor as a confirmatory technique for NSAbs.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"12 4","pages":"e200406"},"PeriodicalIF":7.8,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12153941/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144111486","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":"Neutropenia Associated With B Cell-Depleting Therapies in Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorder.","authors":"Greer Waldrop, Nikki Sisodia, Shane Poole, Samuel Pleasure, Michael R Wilson, Chu-Yueh Guo, Jeffrey M Gelfand, Scott S Zamvil, Riley Bove","doi":"10.1212/NXI.0000000000200430","DOIUrl":"10.1212/NXI.0000000000200430","url":null,"abstract":"<p><strong>Background and objectives: </strong>Neutropenia is described as a rare adverse event associated with B cell-depleting therapy (BCDT) use in patients with multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD). However, little is known about longitudinal clinical outcomes. We estimated the real-world incidence of neutropenia among patients with neuroinflammatory disease treated with BCDT and characterized the clinical course.</p><p><strong>Methods: </strong>We conducted a retrospective cohort study using electronic medical records to estimate the incidence rate of neutropenia in adults with MS/NMOSD from a neuroimmunology clinic in California between January 6, 2006, and November 2, 2015, treated with ocrelizumab, rituximab, ofatumumab, ublituximab, or inebilizumab. Each clinical course (recurrence, time to recovery of absolute neutrophil count [ANC], postneutropenia treatment) of neutropenia was then presented in a case series.</p><p><strong>Results: </strong>In this cohort of 1,825 patients (6,009 person-years on BCDT), the largest cohort addressing this question to date, 37 developed neutropenia. The estimated incidence rate of neutropenia was 0.62 (95% CI 0.45-0.85) per 100 person-years. The median time from last infusion of current BCDT was 4 months (interquartile range [IQR] 1-6). The median nadir ANC was 390 (IQR 40-960); the nadir ANC was 0 for 6 patients (16%). All patients ultimately recovered to normal counts, except 2 patients developing fluctuating ANCs for months. Among the 32 patients not receiving filgrastim, the median time to ANC recovery was 11 days (95% CI 7-26). Course severity was asymptomatic/mild in 32% (n = 12) while 54% (n = 20) required hospitalization. A confirmed simultaneous infection or infectious prodrome occurred in 23 (62%). After recovery, 30 patients (81%) continued BCDT and 2 (7%) changed within BCDT class. Neutropenia recurred in 13 patients (35%), including 3 who discontinued BCDT after initial neutropenia. The estimated incidence rate of recurrent neutropenia was 0.22 (95% CI 0.13-0.39) per 100 person-years. The mean (SD) time to recurrence from initial neutropenia was 251 (SD: 355) days.</p><p><strong>Discussion: </strong>This study is comprehensive and reflects a large cohort, examining incidence rates of neutropenia with BCDT in MS and NMOSD. Overall, neutropenia was still rare, occurring at a rate of 0.66 per 100 person-years, and infections were associated triggers in some patients. Yet, of relevance to clinicians, neutropenia was not benign: half required hospitalization and 35% experienced recurrence, which is higher than what was reported in clinical trials.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"12 4","pages":"e200430"},"PeriodicalIF":7.8,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12185220/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144333579","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}