Neurology® Neuroimmunology & Neuroinflammation最新文献

{"title":"APOSTEL-R Recommendations for Reporting Retinal Optical Coherence Tomography Studies in Rodents.","authors":"Frederike Cosima Oertel, Delia Cabrera Debuc, Peter A Calabresi, Mei Chen, Christian Cordano, Michael Dietrich, Nicolas Feltgen, Oliver Gramlich, Ari J Green, Janos Groh, Su-Chun Huang, Benjamin Knier, Thomas Korn, Letizia Leocani, Anat Loewenstein, Christian van Oterendorp, Tunde Peto, Sven Schippling, Leopold Schmetterer, Steffen Schmitz-Valckenberg, Mathias W Seeliger, Kenneth S Shindler, Joel S Schuman, Mustafa Sindi, Adnan Tufail, Jui-Kai Wang, Sebastian Wolf, Yuyi You, Martin Zinkernagel, Wolf Lagrèze, Philipp Albrecht","doi":"10.1212/NXI.0000000000200489","DOIUrl":"10.1212/NXI.0000000000200489","url":null,"abstract":"<p><strong>Background and objectives: </strong>Retinal optical coherence tomography (OCT) in rodent models has been used to longitudinally image retinal changes, to define end points for more costly or time-consuming experiments, and to better understand the pathophysiology underlying OCT findings in human diseases. No standardization of rodent OCT reporting currently exists. Here, we aim to establish consensus recommendation for reporting results from retinal OCT studies in rodents.</p><p><strong>Methods: </strong>Initial recommendations were developed based on the APOSTEL criteria for quantitative OCT reporting in humans by a core team. Using a modified Delphi process, an expert panel of rodent OCT researchers (N = 31) and the wider scientific community discussed, refined, and voted on these initial recommendations. The list of recommendations was then revised and approved by the expert panel.</p><p><strong>Results: </strong>The final 7-point checklist includes reporting recommendations regarding the study protocol, OCT device, acquisition settings and modifications, scanning protocol, funduscopic imaging, postacquisition data selection and image data analyses, and qualitative and quantitative results. With a median agreement score of 3 or 4 out of 4, the scientific community agreed with these recommendations. After revisions, the expert panel accepted the final recommendations.</p><p><strong>Discussion: </strong>The Advised Protocol for OCT Study Terminology and Elements for reporting OCT studies in rodents (APOSTEL-R) originates from an expert consensus. They will provide guidance throughout the experimental process and will contribute to the standardization and quality improvement of preclinical OCT studies.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"12 6","pages":"e200489"},"PeriodicalIF":7.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12509961/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145252125","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":"Iatrogenic Cerebral Amyloid Angiopathy-Related Inflammation: A Multicenter Case Series.","authors":"Benedetta Storti, Giulia Negro, Giorgia Orsani, Payam Tabaee Damavandi, Marco Donelli, Elisa Cavarsaschi, Elisa Conti, Gessica Sala, Chiara Paola Zoia, Carlo Ferrarese, Mario Stanziano, Isabella Canavero, Anna Bersano, Jacopo C DiFrancesco","doi":"10.1212/NXI.0000000000200470","DOIUrl":"https://doi.org/10.1212/NXI.0000000000200470","url":null,"abstract":"<p><strong>Background and objectives: </strong>Variants of cerebral amyloid angiopathy (CAA) have been increasingly reported. Iatrogenic CAA (iCAA) is a subtype arising in patients with a history of neurosurgery. Current etiopathogenetic hypotheses focus on previous exposure to contaminated materials, such as cadaveric dura, followed by a prion-like mechanism. CAA-related inflammation (CAA-ri) represents the inflammatory variant of CAA, usually with a good response to immunosuppressive therapy. To date, the association between iCAA and CAA-ri has not been clarified yet. This study reports cases of iCAA evolving into CAA-ri, emphasizing the clinical and radiologic overlaps between these conditions.</p><p><strong>Methods: </strong>This retrospective observational study included patients with clinical and radiologic features of CAA-ri and a history of neurosurgical intervention, observed at 2 Italian neurologic centers. Patients were identified from CAA databases and screened for neurosurgical history before 1990. Eligible cases met diagnostic criteria for CAA-ri. Clinical data were anonymized and included surgical details, evidence of amyloid-β in the CNS (amyloid-PET, CSF biomarkers, genetic screening), and CAA-ri features (symptoms, imaging findings, treatment, and outcomes).</p><p><strong>Results: </strong>We identified 6 patients with iCAA who developed clinical and instrumental features of CAA-ri during their follow-up. The mean age at neurosurgery was 17.2 years (range: <1-43) while the onset of CAA-ri occurred at 61.8 years (range: 48-79), with an average latency of 44.7 years (range: 36-59). Despite immunosuppressive treatment, 2 patients experienced a rapid decline in their clinical condition and deceased within a few months from CAA-ri onset.</p><p><strong>Discussion: </strong>This study increases awareness about the potential occurrence of CAA-ri in patients with iCAA, confirming its aggressive nature and highlighting the importance of neuroinflammation in the pathogenesis of the disease. In these patients, CAA-ri seems to be associated with a severe clinical course and a poor response to steroid treatment, often resulting in a fatal outcome in the short term.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"12 6","pages":"e200470"},"PeriodicalIF":7.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145258646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Natalizumab-Associated Progressive Multifocal Leukoencephalopathy After Natalizumab Extended Interval Dosing Therapy in Japan.","authors":"Kazuya Takahashi, Jin Nakahara, Yoshiharu Miura, Ryusuke Ae, Kazuo Nakamichi, Masafumi Harada, Koichiro Mori, Nobuo Sanjo, Motohiro Yukitake, Hiroaki Yokote, Tsuyoshi Hamaguchi, Masahito Yamada, Masaki Takao","doi":"10.1212/NXI.0000000000200476","DOIUrl":"https://doi.org/10.1212/NXI.0000000000200476","url":null,"abstract":"<p><strong>Objective: </strong>To describe 5 confirmed cases of natalizumab-associated progressive multifocal leukoencephalopathy (NTZ-PML) in Japan.</p><p><strong>Methods: </strong>The Nationwide PML Surveillance Committee requires mandatory registration of all natalizumab cases and reporting by affiliated facilities conducting JC DNA testing. Suspected PML cases were reviewed by the committee and classified as definite, probable, possible, or non-PML based on established diagnostic criteria.</p><p><strong>Results: </strong>From 2016 to 2024, the nationwide PML surveillance committee identified 8 NTZ-PML cases, of which 5 (all women and relapsing-remitting types) were registered as clinically definite PML cases. Four cases involved a switch from other disease-modifying drugs, while one involved natalizumab as the first-line treatment for multiple sclerosis (MS). In all cases, extended interval dosing therapy (EID) every 6-8 weeks was administered for at least 1 year before PML onset, and 3 cases had received EID from the outset. At PML onset, the viral DNA levels in the CSF were ≤100 copies/mL in 3 cases.</p><p><strong>Discussion: </strong>Given the high prevalence of JC virus antibody positivity in Japan, additional risk factors may contribute to NTZ-PML susceptibility. Although EID of natalizumab is expected to reduce PML risk, its effectiveness may be limited, particularly in Japanese individuals with high JC virus antibody titers.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"12 6","pages":"e200476"},"PeriodicalIF":7.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12396746/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144963288","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":"Persons With Multiple Sclerosis Reveal Distinct Kynurenine Pathway Metabolite Patterns: A Multinational Cross-Sectional Study.","authors":"Marie Kupjetz, Martin Langeskov-Christensen, Morten Riemenschneider, Stefan Inerle, Uwe Ligges, Tobias Gaemelke, Nadine Patt, Jens Bansi, Roman Rudolf Gonzenbach, Marcel Reuter, Friederike Rosenberger, Tim Meyer, Adrian McCann, Per Magne Ueland, Simon Fristed Eskildsen, Mikkel Karl Emil Nygaard, Niklas Joisten, Lars Hvid, Ulrik Dalgas, Philipp Zimmer","doi":"10.1212/NXI.0000000000200461","DOIUrl":"10.1212/NXI.0000000000200461","url":null,"abstract":"<p><strong>Background and objectives: </strong>Kynurenine pathway (KP) metabolites modulate inflammatory activity and neuronal viability. The consequences of KP imbalance partly resemble the molecular mechanisms of multiple sclerosis (MS). An improved understanding of KP imbalance and its relevance in MS requires holistic approaches beyond single-metabolite investigations. Thus, we aimed to explore the presence of KP metabolite patterns in MS and to evaluate their relevance in relation to participant characteristics and clinical measures.</p><p><strong>Methods: </strong>In this multinational cross-sectional analysis, we determined serum concentrations of KP metabolites in persons with MS and healthy individuals using targeted metabolomics (LC-MS/MS). Analyses were conducted between March 24, 2022, and August 9, 2024. The source studies were conducted in Denmark, Germany, and Switzerland. All participants were aged 18 years or older and free of acute or chronic diseases besides MS. Persons with MS had mild to moderate disease severity (Expanded Disability Status Scale [EDSS] score ≤6.5). Following the investigation of individual metabolites, we explored KP metabolite patterns using exploratory factor analysis. Associations between KP metabolite patterns and participant characteristics, MS symptoms, and MRI metrics were investigated using correlation analyses, proportional odds regression, and multiple linear regression.</p><p><strong>Results: </strong>The MS cohort included 353 participants (67.1% female) with a mean (SD) age of 46.1 (12.4) years. The mean (SD) EDSS score was 3.1 (1.8). The healthy control (HC) cohort included 111 participants (53.2% female) with a mean (SD) age of 45.7 (16.6) years. Persons with MS showed 2 distinct KP metabolite patterns: an inflammation-driven neurotoxic pattern (<i>NeuroTox</i>) and a neuroprotective pattern (<i>NeuroPro</i>). Greater <i>NeuroTox</i> was associated with a higher EDSS score, older age, and higher body fat percentage. Greater <i>NeuroPro</i> was associated with a lower EDSS score and higher cardiorespiratory fitness.</p><p><strong>Discussion: </strong>Using a data-driven approach, we demonstrate the presence of 2 KP metabolite patterns, <i>NeuroTox</i> and <i>NeuroPro</i>, in MS. Greater <i>NeuroTox</i> and lower <i>NeuroPro</i> were both associated with greater disease severity. Future studies need to investigate the KP metabolite patterns across the MS disability spectrum and may use comparable approaches to investigate whether KP imbalance follows similar or disease-specific patterns in diseases other than MS.</p><p><strong>Trial registration information: </strong>NCT03322761, NCT02661555, NCT04762342, NCT04356248, DRKS00017091, DRKS00031445, DRKS00028792, DRKS00029105.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"12 6","pages":"e200461"},"PeriodicalIF":7.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12448327/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145086806","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 Epilepsy and Factors Associated With Time to Seizure Remission in Anti-LGI1 Encephalitis: Long-Term Outcome in 236 Patients.","authors":"Tobias Baumgartner, Moritz Freyberg, Lucia Campetella, Yvette Crijnen, Justina Dargvainiene, Charlotte Behning, Christian G Bien, Anna Rada, Harald Prüss, Rosa Rössling, Stjepana Kovac, Christine Strippel, Franziska S Thaler, Katharina Eisenhut, Jan Lewerenz, Felicitas Becker, Raphael Reinecke, Michael Peter Malter, Kurt-Wolfram Sühs, Simone C Tauber, Felix Von Podewils, Nico Melzer, Klaus-Peter Wandinger, Romina-Anna-Maria Fernandez Ceballos, Jens Kuhle, Klaus Berger, Tobias Bauer, Theodor Rüber, Attila Racz, Albert J Becker, Julika Pitsch, Gregor Kuhlenbäumer, Sergio Muñiz-Castrillo, Jerome Honnorat, Maarten J Titulaer, Frank Leypoldt, Rainer Surges","doi":"10.1212/NXI.0000000000200469","DOIUrl":"10.1212/NXI.0000000000200469","url":null,"abstract":"<p><strong>Background and objectives: </strong>Autoimmune encephalitis (AIE) with anti-leucine-rich glioma-inactivated 1 (LGI1) antibodies typically manifests with subacute cognitive deficits, seizures, and psychiatric symptoms, mostly in older adults. Immunotherapy (IT) leads to the cessation of seizures in most patients, yet some develop AIE-associated epilepsy (AEAE) and persistent cognitive deficits. The aim of this large multicentric retrospective observational cohort study was to assess long-term outcomes of patients with anti-LGI1 encephalitis regarding seizures and AEAE and to identify associated factors.</p><p><strong>Methods: </strong>We included patients with anti-LGI1 encephalitis from 3 national referral centers/consortia meeting the following inclusion criteria: (I) definite LGI1 limbic encephalitis (Graus criteria); (II) occurrence of seizures; and (III) follow-up period ≥24 months. We aimed to (1) determine the risk of seizure recurrence (ROSR) on remission, (2) investigate clinical and paraclinical biomarkers for an effect on time to seizure remission using Cox proportional hazard modeling (n = 188), and (3) assess the risk of AEAE and determine associated factors (n = 236).</p><p><strong>Results: </strong>AEAE was observed in 5.9% (16/271) of the full cohort. Both AEAE (16/16 vs 129/215, <i>p</i> = 0.001) and longer time to seizure remission (OR 1.36 per year, <i>p</i> = 0.025) were associated with persistent cognitive impairment. Patients with pilomotor seizures had a lower rate of seizure remission (hazard ratio [HR] 0.58, 95% CI 0.55-0.60, <i>p</i> < 0.001) while patients under IT administration had a higher rate of seizure remission over time (HR 12.4, 95% CI 9.67-16.0, <i>p</i> < 0.001). In addition, patients receiving second-line IT tended to achieve earlier seizure remission (log-rank test, <i>p</i> = 0.019). The ROSR at 12, 60, and 120 months on seizure remission was 9% (95% CI 4.5%-13%), 20% (95% CI 11%-28%), and 53% (95% CI 14%-74%), respectively.</p><p><strong>Discussion: </strong>In conclusion, our results demonstrate that AEAE in anti-LGI1 encephalitis is rare and suggest that the diagnosis of epilepsy is inappropriate in patients reaching seizure remission because of a relatively low ROSR. Accordingly, on seizure remission, the diagnosis of acute symptomatic seizures would be appropriate. Moreover, we validate and quantify the importance of IT for seizure remission and identify biomarkers associated with lower rates of seizure remission. Late remission of seizures and AEAE were associated with persistent cognitive impairment.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"12 6","pages":"e200469"},"PeriodicalIF":7.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12440303/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145069925","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":"Oral and Gut Dysbiosis in Migraine: Oral Microbial Signatures as Biomarkers of Migraine.","authors":"Soomi Cho, Yeonjae Jung, Hyun-Seok Oh, Jungyon Yum, Seungwon Song, JaeWook Jeong, Woo-Seok Ha, Kyung Min Kim, Won-Joo Kim, Min Kyung Chu","doi":"10.1212/NXI.0000000000200437","DOIUrl":"10.1212/NXI.0000000000200437","url":null,"abstract":"<p><strong>Background and objectives: </strong>Emerging evidence suggests that oral health conditions may exacerbate migraine, and saliva is a potential source of biomarkers for migraine. The 3-way interaction of the oral-gut-brain axis has been implicated in several neurologic disorders, but has rarely been studied in migraine. This study examined the oral and gut microbiomes simultaneously and identified several key oral microbes that may influence migraine.</p><p><strong>Methods: </strong>In this cross-sectional case-control study, participants were divided into 3 groups: episodic migraine (n = 55), chronic migraine (n = 55), and healthy control (HC) (n = 55). Demographic and clinical characteristics; lifestyle factors; and biological samples including saliva, stool, and blood were collected. Composition, function, and community type of the oral and gut microbiomes were compared among the 3 groups.</p><p><strong>Results: </strong>Oral dysbiosis was more pronounced than gut dysbiosis in the migraine groups, with 13 oral genera significantly enriched or depleted compared with HCs. The migraine groups showed increased abundance of <i>Gemella</i>, <i>Streptococcus</i>, <i>Granulicatella</i>, and <i>Rothia</i> and decreased abundance of <i>Alloprevotella</i>, <i>Veillonella</i>, <i>Haemophilus</i>, <i>Selenomonas</i>, <i>Campylobacter</i>, <i>Cardiobacterium</i>, <i>Megasphaera</i>, and <i>Kingella</i> after adjustment for demographic and lifestyle factors including diet. The enriched oral genera within the migraine groups were associated with carbohydrate metabolic pathways, whereas the depleted oral genera were associated with pathways related to nitrogen. A significant proportion of the oral microbial signatures of migraine included genera capable of reducing nitrate and/or nitrite. Some of these oral microbial signatures of migraine had a relative abundance that was positively or negatively associated with the number of headache days per 30 days and formed distinct microbial clusters in both the oral cavity and gut. Machine learning classifiers using the oral microbiome effectively classified migraine status, with an area under the receiver-operating characteristic curve of 0.83-0.88.</p><p><strong>Discussion: </strong>Our findings suggest that oral dysbiosis may be involved in the development of migraine and highlight specific oral microbes as potential diagnostic biomarkers and therapeutic targets for migraine.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"12 5","pages":"e200437"},"PeriodicalIF":7.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12221161/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144699181","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":"Elevated ITGAX/CD11c in CSF-Derived Extracellular Vesicles Reflects Disability Progression in Multiple Sclerosis.","authors":"Naotoshi Iwahara, Satoshi Muraoka, Taro Saito, Masayo Hirano, Kazuki Yokokawa, Masanobu Tanemoto, Ryosuke Oda, Takayuki Nonaka, Shuuichirou Suzuki, Jun Adachi, Shin Hisahara","doi":"10.1212/NXI.0000000000200442","DOIUrl":"10.1212/NXI.0000000000200442","url":null,"abstract":"<p><strong>Background and objectives: </strong>Extracellular vesicles (EVs) are membrane-bound particles that are released into the extracellular space and are believed to play a role in the pathogenesis of neuroinflammation and neurodegeneration. Nevertheless, the precise role of these vesicles in the context of multiple sclerosis (MS) remains uncertain. The objective of this study was to identify the distinctive characteristics of EVs associated with MS.</p><p><strong>Methods: </strong>EVs were isolated from CSF using phosphatidylserine affinity methods. Mass spectrometry was used to analyze CSF samples and EVs isolated from those CSF samples collected from a discovery cohort of 10 patients with other neurologic diseases (ONDs) and 10 patients with MS. In addition, mass spectrometry was used to analyze EVs isolated from CSF samples in a validation cohort of 24 patients with ONDs, 38 patients with MS, and 14 patients with neuromyelitis optica spectrum disorders.</p><p><strong>Results: </strong>The results revealed notable increases in the levels of 33 proteins in the CSF samples and 100 proteins in the CSF-derived EVs from patients with MS in the validation cohort. Increases in the levels of ITGA4, ITGAX (CD11c), MS4A1 (CD20), CD3E, CD4, and CD8A, which are marker proteins of lymphocytes and myeloid cells, including activated microglia and dendritic cells, were observed in the CSF-derived EVs in the discovery cohort. The results of the validation cohort revealed that the levels of 4 proteins, ITGA4, ITGAX, MS4A1, and CD3E, were significantly greater in patients with MS than in patients with ONDs. Furthermore, the level of ITGAX was greater in the patients with confirmed disability worsening (CDW) than in those without CDW. The results of the receiver operating characteristic (ROC) and Kaplan-Meier analyses indicated that ITGAX levels in CSF-derived EVs may prove useful in predicting disease prognosis.</p><p><strong>Discussion: </strong>Our findings suggest that CSF-derived EVs reflect immunologic changes in MS and other neuroimmune diseases. In addition, these results raise the possibility that changing in myeloid cells and lymphocytes may also play a role in the pathogenesis of MS. CSF-derived EVs may serve as indicators of MS disease severity and could be used as biomarkers in the future.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"12 5","pages":"e200442"},"PeriodicalIF":7.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12275904/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144663974","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":"Cerebrospinal 14-3-3 Protein Levels as a Neuroaxonal Biomarker in Aquaporin-4 Antibody-Positive Neuromyelitis Optica Spectrum Disorder.","authors":"Javier Villacieros-Álvarez, Maria Sepulveda, Adrián Valls-Carbó, Nicolas Fissolo, Alessandro Dinoto, Victoria Fernández, Andreu Vilaseca, Georgina Arrambide, Lucia Gutierrez, Mireia Castillo, Luca Bollo, Carmen Espejo, Sara Llufriu, Yolanda Blanco, Thais Armangue, Gary Álvarez Bravo, Ana Quiroga-Varela, Lluís Ramió Torrentà, Alvaro Cobo-Calvo, Mar Tintore, Jan D Lünemann, Albert Saiz, Sara Mariotto, Xavier Montalban, Manuel Comabella","doi":"10.1212/NXI.0000000000200432","DOIUrl":"10.1212/NXI.0000000000200432","url":null,"abstract":"<p><strong>Background and objectives: </strong>To investigate whether CSF 14-3-3 protein levels discriminate aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder (AQP4-NMOSD) from myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) and multiple sclerosis (MS) and the association of CSF 14-3-3 protein levels with clinical features in patients with AQP4-NMOSD.</p><p><strong>Methods: </strong>This was a multicentric retrospective cohort study of patients with AQP4-NMOSD, MOGAD, and MS, with available CSF samples. 14-3-3 protein levels were quantified using ELISA and compared between the 3 conditions. In patients with AQP4-NMOSD, the association between CSF 14-3-3 protein levels and disability outcomes was explored.</p><p><strong>Results: </strong>A total of 134 patients were included (AQP4-NMOSD, n = 29; MOGAD, n = 43; MS, n = 62). Patients with AQP4-NMOSD had higher 14-3-3 protein levels (median [interquartile range] 4,441.37 [3,240.05-11526.41] arbitrary units (AU)/mL) compared with those with MS (3,169.86 [2,522.65-3,748.57], <i>p</i> = 0.001) and MOGAD (3,112.95 [2,367.37-3,889.43], <i>p</i> = 0.004). Patients with AQP4-NMOSD presenting with optic neuritis had lower 14-3-3 levels compared with those with other phenotypes (<i>p</i> < 0.001). In AQP4-NMOSD, 14-3-3 levels associated with Expanded Disability Status Scale (EDSS) at attack (β [95%CI] 0.33 [0.15-0.52], <i>p</i> = 0.003) and predicted final EDSS ≥ 6.0 (odds ratio 9.48 [1.69; 194.34]; <i>p</i> = 0.041) in patients with myelitis.</p><p><strong>Discussion: </strong>The study suggests a potential role of CSF 14-3-3 protein levels as a biomarker of neuroaxonal damage in AQP4-NMOSD, because of its ability to correlate with disease severity and predict poor clinical recovery.</p><p><strong>Classification of evidence: </strong>This study provides Class IV evidence that in individuals presenting with acute myelitis, CSF 14-3-3 differentiates AQP4-NMOSD from MS or MOGAD with a sensitivity of 0.60 (0.30-0.80) and specificity of 0.95 (0.84-1.00).</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"12 5","pages":"e200432"},"PeriodicalIF":7.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12221159/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144529041","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":"N-Glycan-Dependent Proinflammatory Effects of IgM in Anti-MAG Neuropathy.","authors":"Jean Neil, François Fenaille, Arnaud Bruneel, Tanya Stojkovic, Sophie Cholet, Emilien Delmont, Pauline Ober, Alexandre Raynor, Quentin Amiot, Karim Dorgham, Karine Viala, Pascale Ghillani-Dalbin, Guy Gorochov, Delphine Sterlin","doi":"10.1212/NXI.0000000000200440","DOIUrl":"10.1212/NXI.0000000000200440","url":null,"abstract":"<p><strong>Background and objectives: </strong>Anti-myelin-associated glycoprotein (anti-MAG) neuropathy is a chronic demyelinating neuropathy with deposits of IgM and sural nerve fiber demyelination. While growing evidence supports the critical role of IgG glycosylation in autoimmune diseases, IgM glycosylation profiles markedly differ from those of IgG but are largely neglected. The aim of this study was to characterize IgM N-glycosylation in patients with anti-MAG neuropathy and its involvement in anti-MAG pathogenicity.</p><p><strong>Methods: </strong>IgM antibodies were isolated from patients with anti-MAG neuropathy (n = 17), asymptomatic patients with monoclonal gammopathy of undetermined significance (n = 8), and healthy donors ([HDs], n = 6). N-glycan analysis was performed using mass spectrometry. Binding to myelin-associated glycoprotein (MAG), complement (C1q), and IgM Fc receptors (Fcα/μR and DC-SIGN) was compared using ELISA between anti-MAG and MGUS IgM, before and after N-deglycosylation/desialylation. Finally, we assessed how IgM N-glycosylation influences cytokine production by monocyte-derived macrophages by measuring cytokine levels in culture supernatants.</p><p><strong>Results: </strong>Anti-MAG IgM exhibited a unique glycosylation pattern, dominated by fucosylated, monosialylated N-glycan with a bisecting N-acetyl glucosamine (N-glycan 12), representing 48.5% of the total N-glycan pool, compared with 27.3% in MGUS IgM and 35.6% in HD IgM. We showed that deglycosylation and desialylation significantly reduced anti-MAG activity and C1q binding (average % of decrease 58.3 ± 18.8, <i>p</i> < 0.01, and 40.0 ± 19.9%, <i>p</i> < 0.05, respectively). Furthermore, anti-MAG IgM binding to C1q was significantly higher than that of MGUS IgM and HD IgM (<i>p</i> < 0.0001 and <i>p</i> < 0.001, respectively). Compared with MGUS IgM, anti-MAG IgM also significantly increased the production of proinflammatory cytokines IL-1, IL-6, IL-8, TNF-α, and IFN-Υ by macrophages, in a glycan-dependent manner (<i>p</i> < 0.01 to <i>p</i> < 0.001), with IL-8 being particularly elevated. Finally, we found that anti-MAG IgM bound more strongly Fcα/μ receptor and DC-SIGN compared with MGUS IgM (<i>p</i> < 0.05 and <i>p</i> = 0.06).</p><p><strong>Discussion: </strong>This study uncovered a unique N-glycosylation pattern of anti-MAG IgM, crucial for its interaction with MAG and binding to C1q. Moreover, anti-MAG IgM increased the macrophage cytokine production, driven by their glycosylation. The increased IL-8 expression and anti-MAG IgM binding to C1q might open 2 potential therapeutic avenues: inhibiting IL-8 activity or targeting the complement pathway. In addition, the glycosylation and C1q binding of anti-MAG IgM could serve as biomarkers for monitoring this neuropathy.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"12 5","pages":"e200440"},"PeriodicalIF":7.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12316464/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144760652","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":"Neuronal Autoantibodies in Adults After Community-Acquired Bacterial Meningitis.","authors":"Steven L Staal, Liora Ter Horst, Juliette Brenner, Diederik van de Beek, Maarten J Titulaer, Matthijs C Brouwer","doi":"10.1212/NXI.0000000000200454","DOIUrl":"10.1212/NXI.0000000000200454","url":null,"abstract":"<p><strong>Background and objectives: </strong>Long-term cognitive impairment is observed in 14%-32% of patients surviving community-acquired bacterial meningitis. We hypothesized that the impairment might be linked to secondary immune activation due to the development of neuronal autoantibodies, similar to postinfectious autoimmune encephalitis after viral encephalitis.</p><p><strong>Methods: </strong>In this cross-sectional observational study, we included adult patients from a prospective, nationwide cohort study of community-acquired bacterial meningitis in the Netherlands, the MeninGene study. The presence of neuronal autoantibodies was evaluated in follow-up serum samples at 7 days, at 3 months, or over a year. Immunohistochemistry on complete rat brain slices was performed for the initial screening. If positive or ambiguous, immunocytochemistry using live primary rat hippocampal neurons and cell-based assays expressing extracellular targets were performed; immunoblots were used for intracellular targets.</p><p><strong>Results: </strong>In total, 118 patients were included, of whom 24 of 100 (24%) had cognitive impairment and 14 of 109 (13%) had focal neurologic deficits at discharge. Causative pathogens were <i>Streptococcus pneumoniae</i> in 98 patients (83%), <i>Neisseria meningitidis</i> in 4 (3%), and other pathogens in 6 (5%); in 10 patients (9%), no causative pathogen was identified. Two of 118 patients (2%) had neuronal autoantibodies in follow-up serum: 1 had leucine-rich glioma inactivated 1 antibodies, and 1 had unspecified antibodies. None of the patients was positive for NMDA receptor antibodies.</p><p><strong>Discussion: </strong>There was no clear evidence of postinfectious autoimmune encephalitis after bacterial meningitis. Therefore, acute brain damage caused by the infection itself seems to be the most plausible explanation for long-term cognitive impairment and neurologic disabilities.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"12 5","pages":"e200454"},"PeriodicalIF":7.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12270495/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144650035","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}