Neurology® Neuroimmunology & Neuroinflammation最新文献

{"title":"Life-Threatening MOG Antibody-Associated Hemorrhagic ADEM With Elevated CSF IL-6.","authors":"Akash Virupakshaiah, Carson E Moseley, Steven Elicegui, Lee M Gerwitz, Collin M Spencer, Elizabeth George, Maulik Shah, Bruce A C Cree, Emmanuelle Waubant, Scott S Zamvil","doi":"10.1212/NXI.0000000000200243","DOIUrl":"10.1212/NXI.0000000000200243","url":null,"abstract":"<p><p>Acute disseminated encephalomyelitis (ADEM) is one characteristic manifestation of myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). A previously healthy man presented with retro-orbital headache and urinary retention 14 days after Tdap vaccination. Brain and spine MRI suggested a CNS demyelinating process. Despite treatment with IV steroids, he deteriorated, manifesting hemiparesis and later impaired consciousness, requiring intubation. A repeat brain MRI demonstrated new bilateral supratentorial lesions associated with venous sinus thrombosis, hemorrhage, and midline shift. Anti-MOG antibody was present at a high titer. CSF IL-6 protein was >2,000 times above the upper limits of normal. He improved after plasma exchange, then began monthly treatment alone with anti-IL-6 receptor antibody, tocilizumab, and has remained stable. This case highlights how adult-onset MOGAD, like childhood ADEM, can rapidly become life-threatening. The markedly elevated CSF IL-6 observed here supports consideration for evaluating CSF cytokines more broadly in patients with acute MOGAD.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"11 4","pages":"e200243"},"PeriodicalIF":8.8,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11087044/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140870120","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":"Risk of Seizure Recurrence Due to Autoimmune Encephalitis With NMDAR, LGI1, CASPR2, and GABA_BR Antibodies: Implications for Return to Driving.","authors":"Anna Rada, Anne Hagemann, Charlotte Aaberg Poulsen, Tobias Baumgartner, Timea Berki, Morten Blaabjerg, Juliette Brenner, Jeffrey W Britton, Andrew Christiana, Nicolás L Ciano-Petersen, Yvette Crijnen, Martin Elišák, Antonio Farina, Alec R Friedman, Zsófia Hayden, Julien Hébert, Martin Holtkamp, Zhen Hong, Jerome Honnorat, Maria Ilyas-Feldmann, Sarosh R Irani, Stjepana Kovac, Petr Marusic, Sergio Muñiz-Castrillo, Sudarshini Ramanathan, Kelsey M Smith, Claude Steriade, Christine Strippel, Rainer Surges, Maarten J Titulaer, Christopher E Uy, Juna M de Vries, Christian G Bien, Ulrich Specht","doi":"10.1212/NXI.0000000000200225","DOIUrl":"10.1212/NXI.0000000000200225","url":null,"abstract":"<p><strong>Background and objectives: </strong>Patients with ongoing seizures are usually not allowed to drive. The prognosis for seizure freedom is favorable in patients with autoimmune encephalitis (AIE) with antibodies against NMDA receptor (NMDAR), leucine-rich glioma-inactivated 1 (LGI1), contactin-associated protein-like 2 (CASPR2), and the gamma-aminobutyric-acid B receptor (GABA_BR). We hypothesized that after a seizure-free period of 3 months, patients with AIE have a seizure recurrence risk of <20% during the subsequent 12 months. This would render them eligible for noncommercial driving according to driving regulations in several countries.</p><p><strong>Methods: </strong>This retrospective multicenter cohort study analyzed follow-up data from patients aged 15 years or older with seizures resulting from NMDAR-, LGI1-, CASPR2-, or GABA_BR-AIE, who had been seizure-free for ≥3 months. We used Kaplan-Meier (KM) estimates for the seizure recurrence risk at 12 months for each antibody group and tested for the effects of potential covariates with regression models.</p><p><strong>Results: </strong>We included 383 patients with NMDAR-, 440 with LGI1-, 114 with CASPR2-, and 44 with GABA_BR-AIE from 14 international centers. After being seizure-free for 3 months after an initial seizure period, we calculated the probability of remaining seizure-free for another 12 months (KM estimate) as 0.89 (95% confidence interval [CI] 0.85-0.92) for NMDAR, 0.84 (CI 0.80-0.88) for LGI1, 0.82 (CI 0.75-0.90) for CASPR2, and 0.76 (CI 0.62-0.93) for GABA_BR.</p><p><strong>Discussion: </strong>Taking a <20% recurrence risk within 12 months as sufficient, patients with NMDAR-AIE and LGI1-AIE could be considered eligible for noncommercial driving after having been seizure-free for 3 months.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"11 4","pages":"e200225"},"PeriodicalIF":7.8,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11160480/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141262340","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":"Interleukin-6 Signaling Blockade Induces Regulatory Plasmablasts in Neuromyelitis Optica Spectrum Disorder.","authors":"Ritsu Akatani, Norio Chihara, Atsushi Hara, Asato Tsuji, Shusuke Koto, Kazuhiro Kobayashi, Tatsushi Toda, Riki Matsumoto","doi":"10.1212/NXI.0000000000200266","DOIUrl":"10.1212/NXI.0000000000200266","url":null,"abstract":"<p><strong>Background and objectives: </strong>Interleukin-6 receptor antibodies (IL-6R Abs), including satralizumab, are increasingly used to prevent relapse for neuromyelitis optica spectrum disorder (NMOSD). However, the detailed mechanism of action of this treatment on the lymphocyte phenotype remains unclear. This study focused on B cells in patients with NMOSD, hypothesizing that IL-6R Ab enables B cells to acquire regulatory functions by producing the anti-inflammatory cytokine IL-10.</p><p><strong>Methods: </strong>Peripheral blood mononuclear cells were stimulated in vitro to induce the expansion of B-cell subsets, double-negative B cells (DNs; CD19⁺ IgD^-, CD27^-) and plasmablasts (PBs; CD19⁺, CD27^hi, CD38^hi). Whole B cells, DNs, or PBs were isolated after culture with IL-6R Ab, and IL-10 expression was quantified using quantitative PCR and a cytometric bead array. RNA sequencing was performed to identify the marker of regulatory PBs induced by IL-6R Ab.</p><p><strong>Results: </strong>DNs and PBs were observed to expand in patients with NMSOD during the acute attacks. In the in vitro model, IL-6R Ab increased IL-10 expression in B cells. Notably, IL-10 expression increased in PBs but not in DNs. Using RNA sequencing, CD200 was identified as a marker of regulatory PBs among the differentially expressed upregulated genes. CD200⁺ PBs produced more IL-10 than CD200^- PBs. Furthermore, patients with NMOSD who received satralizumab had a higher proportion of CD200⁺ PBs than patients during the acute attacks.</p><p><strong>Discussion: </strong>Treatment with IL-6 signaling blockade elicited a regulatory phenotype in B cells and PBs. CD200⁺ PBs may be a marker of treatment responsiveness in the context of NMOSD pathophysiology.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"11 4","pages":"e200266"},"PeriodicalIF":7.8,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11188987/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141420053","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":"Advancing Knowledge in CNS Vasculitis.","authors":"Christian Pagnoux, Hubert de Boysson","doi":"10.1212/NXI.0000000000200272","DOIUrl":"10.1212/NXI.0000000000200272","url":null,"abstract":"","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"11 4","pages":"e200272"},"PeriodicalIF":7.8,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11194713/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141301108","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":"Neonatal B-Cell Levels and Infant Health in Newborns Potentially Exposed to Anti-CD20 Monoclonal Antibodies During Pregnancy or Lactation.","authors":"Carolin Schwake, Julia Steinle, Sandra Thiel, Nina Timmesfeld, Sabrina Haben, Ilya Ayzenberg, Ralf Gold, Kerstin Hellwig","doi":"10.1212/NXI.0000000000200264","DOIUrl":"10.1212/NXI.0000000000200264","url":null,"abstract":"<p><strong>Objectives: </strong>To report CD19⁺ B-cell counts and possible adverse effects on infants of mothers exposed to anti-CD20 mAbs ≤6 months before/during pregnancy or lactation.</p><p><strong>Methods: </strong>We conducted a retrospective study using data from the German nationwide neuroimmunologic pregnancy registry. Inclusion criteria involved infants whose mothers received anti-CD20 mAbs ≤6 months before/during pregnancy or lactation, with ≥1 postnatal CD19⁺ B-cell count. Main outcomes were absolute and relative CD19⁺ B-cell counts. Comparison with reference values was performed conservatively in a subgroup with maternal exposure ≤3 months before/during pregnancy. Additional outcomes included pregnancy results, severe infections, and lymphocyte counts.</p><p><strong>Results: </strong>The cohort comprised 49 infants (F:M 25:24) exposed to anti-CD20 mAbs ≤6 months before/during pregnancy or lactation. CD19⁺ B-cell and lymphocyte counts in 40 infants with maternal exposure ≤3 months before/during pregnancy were comparable with normative values. Only 2 cases of complete CD19⁺ B-cell depletion occurred after second-trimester and third-trimester ocrelizumab exposure, with repopulation observed within 2 months. Exclusive lactation exposure had no significant effect on infants' absolute CD19⁺ B-cell counts.</p><p><strong>Discussion: </strong>Administering anti-CD20 mAbs before or at the pregnancy onset, or during lactation, seems safe without significant impact on infant B-cell development. However, second-trimester or third-trimester exposure can cause CD19⁺ B-cell depletion due to placental transfer, necessitating monitoring and postponing live vaccines.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"11 4","pages":"e200264"},"PeriodicalIF":7.8,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11178251/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141317893","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":"Ocrelizumab Alters Cytotoxic Lymphocyte Function While Reducing EBV-Specific CD8⁺ T-Cell Proliferation in Patients With Multiple Sclerosis.","authors":"Gianmarco Abbadessa, Maria Teresa Lepore, Sara Bruzzaniti, Erica Piemonte, Giuseppina Miele, Elisabetta Signoriello, Francesco Perna, Chiara De Falco, G Lus, Giuseppe Matarese, Simona Bonavita, Mario Galgani","doi":"10.1212/NXI.0000000000200250","DOIUrl":"10.1212/NXI.0000000000200250","url":null,"abstract":"<p><strong>Background and objectives: </strong>The role of B cells in the pathogenic events leading to relapsing multiple sclerosis (R-MS) has only been recently elucidated. A pivotal step in defining this role has been provided by therapeutic efficacy of anti-CD20 monoclonal antibodies. Indeed, treatment with anti-CD20 can also alter number and function of other immune cells not directly expressing CD20 on their cell surface, whose activities can contribute to unknown aspects influencing therapeutic efficacy. We examined the phenotype and function of cytotoxic lymphocytes and Epstein-Barr virus (EBV)-specific immune responses in people with R-MS before and after ocrelizumab treatment.</p><p><strong>Methods: </strong>In this prospective study, we collected blood samples from people with R-MS (n = 41) before and 6 and 12 months after initiating ocrelizumab to assess the immune phenotype and the indirect impact on cytotoxic functions of CD8⁺ T and NK cells. In addition, we evaluated the specific anti-EBV proliferative responses of both CD8⁺ T and NK lymphocytes as surrogate markers of anti-EBV activity.</p><p><strong>Results: </strong>We observed that while ocrelizumab depleted circulating B cells, it also reduced the expression of activation and migratory markers on both CD8⁺ T and NK cells as well as their in vitro cytotoxic activity. A comparable pattern in the modulation of immune molecules by ocrelizumab was observed in cytotoxic cells even when patients with R-MS were divided into groups based on their prior disease-modifying treatment. These effects were accompanied by a significant and selective reduction of CD8⁺ T-cell proliferation in response to EBV antigenic peptides.</p><p><strong>Discussion: </strong>Taken together, our findings suggest that ocrelizumab-while depleting B cells-affects the cytotoxic function of CD8⁺ and NK cells, whose reduced cross-activity against myelin antigens might also contribute to its therapeutic efficacy during MS.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"11 4","pages":"e200250"},"PeriodicalIF":8.8,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11087045/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140850873","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":"Central Vein Sign, Cortical Lesions, and Paramagnetic Rim Lesions for the Diagnostic and Prognostic Workup of Multiple Sclerosis.","authors":"Serena Borrelli, Maria Sofia Martire, Anna Stölting, Colin Vanden Bulcke, Edoardo Pedrini, François Guisset, Céline Bugli, Halil Yildiz, Lucie Pothen, Sophie Elands, Vittorio Martinelli, Bryan Smith, Steven Jacobson, Renaud A Du Pasquier, Vincent Van Pesch, Massimo Filippi, Daniel S Reich, Martina Absinta, Pietro Maggi","doi":"10.1212/NXI.0000000000200253","DOIUrl":"10.1212/NXI.0000000000200253","url":null,"abstract":"<p><strong>Background and objectives: </strong>The diagnosis of multiple sclerosis (MS) can be challenging in clinical practice because MS presentation can be atypical and mimicked by other diseases. We evaluated the diagnostic performance, alone or in combination, of the central vein sign (CVS), paramagnetic rim lesion (PRL), and cortical lesion (CL), as well as their association with clinical outcomes.</p><p><strong>Methods: </strong>In this multicenter observational study, we first conducted a cross-sectional analysis of the CVS (proportion of CVS-positive lesions or simplified determination of CVS in 3/6 lesions-Select3*/Select6*), PRL, and CL in MS and non-MS cases on 3T-MRI brain images, including 3D T2-FLAIR, T2*-echo-planar imaging magnitude and phase, double inversion recovery, and magnetization prepared rapid gradient echo image sequences. Then, we longitudinally analyzed the progression independent of relapse and MRI activity (PIRA) in MS cases over the 2 years after study entry. Receiver operating characteristic curves were used to test diagnostic performance and regression models to predict diagnosis and clinical outcomes.</p><p><strong>Results: </strong>The presence of ≥41% CVS-positive lesions/≥1 CL/≥1 PRL (optimal cutoffs) had 96%/90%/93% specificity, 97%/84%/60% sensitivity, and 0.99/0.90/0.77 area under the curve (AUC), respectively, to distinguish MS (n = 185) from non-MS (n = 100) cases. The Select3*/Select6* algorithms showed 93%/95% specificity, 97%/89% sensitivity, and 0.95/0.92 AUC. The combination of CVS, CL, and PRL improved the diagnostic performance, especially when Select3*/Select6* were used (93%/94% specificity, 98%/96% sensitivity, 0.99/0.98 AUC; <i>p</i> = 0.002/<i>p</i> < 0.001). In MS cases (n = 185), both CL and PRL were associated with higher MS disability and severity. Longitudinal analysis (n = 61) showed that MS cases with >4 PRL at baseline were more likely to experience PIRA at 2-year follow-up (odds ratio 17.0, 95% confidence interval: 2.1-138.5; <i>p</i> = 0.008), whereas no association was observed between other baseline MRI measures and PIRA, including the number of CL.</p><p><strong>Discussion: </strong>The combination of CVS, CL, and PRL can improve MS differential diagnosis. CL and PRL also correlated with clinical measures of poor prognosis, with PRL being a predictor of disability accrual independent of clinical/MRI activity.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"11 4","pages":"e200253"},"PeriodicalIF":7.8,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11129678/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141094083","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":"Corrections to Preprint Server Information.","authors":"","doi":"10.1212/NXI.0000000000200267","DOIUrl":"10.1212/NXI.0000000000200267","url":null,"abstract":"","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"11 4","pages":"e200267"},"PeriodicalIF":7.8,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11195433/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140956839","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":"Alterations of Thymus-Derived Tregs in Multiple Sclerosis.","authors":"Tiziana Lorenzini, Wolfgang Faigle, Josefine Ruder, María José Docampo, Lennart Opitz, Roland Martin","doi":"10.1212/NXI.0000000000200251","DOIUrl":"10.1212/NXI.0000000000200251","url":null,"abstract":"<p><strong>Background and objectives: </strong>Multiple sclerosis (MS) is considered a prototypic autoimmune disease of the CNS. It is the leading cause of chronic neurologic disability in young adults. Proinflammatory B cells and autoreactive T cells both play important roles in its pathogenesis. We aimed to study alterations of regulatory T cells (Tregs), which likely also contribute to the disease, but their involvement is less clear.</p><p><strong>Methods: </strong>By combining multiple experimental approaches, we examined the Treg compartments in 41 patients with relapsing-remitting MS and 17 healthy donors.</p><p><strong>Results: </strong>Patients with MS showed a reduced frequency of CD4⁺ T cells and Foxp3+ Tregs and age-dependent alterations of Treg subsets. Treg suppressive function was compromised in patients, who were treated with natalizumab, while it was unaffected in untreated and anti-CD20-treated patients. The changes in natalizumab-treated patients included increased proinflammatory cytokines and an altered transcriptome in thymus-derived (t)-Tregs, but not in peripheral (p)-Tregs.</p><p><strong>Discussion: </strong>Treg dysfunction in patients with MS might be related to an altered transcriptome of t-Tregs and a proinflammatory environment. Our findings contribute to a better understanding of Tregs and their subtypes in MS.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"11 4","pages":"e200251"},"PeriodicalIF":8.8,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11160584/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141262317","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":"Positive Allosteric Modulation of NMDARs Prevents the Altered Surface Dynamics Caused by Patients' Antibodies.","authors":"Estibaliz Maudes, Zoë Jamet, Laura Marmolejo, Josep O Dalmau, Laurent Groc","doi":"10.1212/NXI.0000000000200261","DOIUrl":"10.1212/NXI.0000000000200261","url":null,"abstract":"<p><strong>Objectives: </strong>A positive allosteric modulator of the NMDAR, SGE-301, has been shown to reverse the alterations caused by the antibodies of patients with anti-NMDAR encephalitis (NMDARe). However, the mechanisms involved beyond receptor modulation are unclear. In this study, we aimed to investigate how this modulator affects NMDAR membrane dynamics.</p><p><strong>Methods: </strong>Cultured hippocampal neurons were treated with SGE-301 or vehicle, alongside with immunoglobulins G (IgG) from patients with NMDARe or healthy controls. NMDAR surface dynamics were assessed with single-molecule imaging by photoactivated localization microscopy.</p><p><strong>Results: </strong>NMDAR trajectories from neurons treated with SGE-301 were less confinement, with increased diffusion coefficients. This effect mainly occurred at synapses because extrasynaptic diffusion and confinement were minimally affected by SGE-301. Treatment with patients' IgG reduced NMDAR surface dynamics and increased their confinement. Remarkably, SGE-301 incubation antagonized patients' IgG effects in both synaptic and extrasynaptic membrane compartments, restoring diffusion and confinement values similar to those from neurons exposed to control IgG.</p><p><strong>Discussion: </strong>We demonstrate that SGE-301 upregulates NMDAR surface diffusion and antagonizes the pathogenic effects of patients' IgG on NMDAR membrane organization. These findings suggest a potential therapeutic strategy for NMDARe.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"11 4","pages":"e200261"},"PeriodicalIF":8.8,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11111324/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141076381","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}