Neurology® Neuroimmunology & Neuroinflammation最新文献

{"title":"Absence of Pathogenic Mutations and Strong Association With HLA-DRB1*11:01 in Statin-Naïve Early-Onset Anti-HMGCR Necrotizing Myopathy.","authors":"Laura Llansó, Alba Segarra-Casas, Cristina Domínguez-González, Edoardo Malfatti, Solange Kapetanovic, Benjamín Rodríguez-Santiago, Oscar de la Calle, Rosa Blanco, Amelia Dobrescu, Andrés Nascimento-Osorio, Andrés Paipa, Aurelio Hernandez-Lain, Cristina Jou, Anaís Mariscal, Laura González-Mera, Ana Arteche, Cinta Lleixà, Marta Caballero-Ávila, Álvaro Carbayo, Ana Vesperinas, Luis Querol, Eduard Gallardo, Montse Olivé","doi":"10.1212/NXI.0000000000200285","DOIUrl":"10.1212/NXI.0000000000200285","url":null,"abstract":"<p><strong>Background and objectives: </strong>Immune-mediated necrotizing myopathy (IMNM) caused by antibodies against 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) is an inflammatory myopathy that has been epidemiologically correlated with previous statin exposure. We characterized in detail a series of 11 young statin-naïve patients experiencing a chronic disease course mimicking a limb-girdle muscular dystrophy. With the hypothesis that HMGCR upregulation may increase immunogenicity and trigger the production of autoantibodies, our aim was to expand pathophysiologic knowledge of this distinct phenotype.</p><p><strong>Methods: </strong>Clinical and epidemiologic data, autoantibody titers, creatine kinase (CK) levels, response to treatment, muscle imaging, and muscle biopsies were assessed. HMGCR expression in patients' muscle was assessed by incubating sections of affected patients with purified anti-HMGCR+ serum. Whole-exome sequencing (WES) with a special focus on cholesterol biosynthesis-related genes and high-resolution human leukocyte antigen (HLA) typing were performed.</p><p><strong>Results: </strong>Patients, aged 3-25 years and mostly female (90.9%), presented with subacute proximal weakness progressing over many years and high CK levels (>1,000 U/L). Diagnostic delay ranged from 3 to 27 years. WES did not reveal any pathogenic variants. HLA-DRB1*11:01 carrier frequency was 60%, a significantly higher proportion than in the control population. No upregulation or mislocalization of the enzyme in statin-exposed or statin-naïve anti-HMGCR+ patients was observed, compared with controls.</p><p><strong>Discussion: </strong>WES of a cohort of patients with dystrophy-like anti-HMGCR IMNM did not reveal any common rare variants of any gene, including cholesterol biosynthesis-related genes. HLA analysis showed a strong association with HLA-DRB1*11:01, previously mostly described in statin-exposed adult patients; consequently, a common immunogenic predisposition should be suspected, irrespective of statin exposure. Moreover, we were unable to conclusively demonstrate muscle upregulation/mislocalization of HMGCR in IMNM, whether or not driven by statins.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"11 5","pages":"e200285"},"PeriodicalIF":7.8,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11309561/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141897935","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":"Antibodies Against ZSCAN1 in Pediatric and Adult Patients With Non-Paraneoplastic ROHHAD Syndrome.","authors":"Ana Beatriz Serafim, Gemma Olivé-Cirera, Ángel Ortega-González, Michael C Kruer, Debra Weese-Mayer, Casey M Rand, Carmen Fons, Joaquín Alejandro Fernández-Ramos, Maria Clemente, Mateus Mistieri Simabukuro, Emilia Katiane Embiruçu, Salvador Ibáñez-Micó, Josep O Dalmau, Francesc Graus, Thais Armangué, Lidia Sabater","doi":"10.1212/NXI.0000000000200276","DOIUrl":"10.1212/NXI.0000000000200276","url":null,"abstract":"<p><strong>Objectives: </strong>To report the association of zinc finger and SCAN domain containing 1 antibodies (ZSCAN1-abs) with rapid-onset obesity, hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD) syndrome in patients without tumor.</p><p><strong>Methods: </strong>Patients with symptoms compatible with ROHHAD syndrome but without an associated tumor were selected from our database. Serum and CSF samples were examined for the presence of ZSCAN1-abs by an in-house cell-based assay. In addition, samples from 149 patients with several inflammatory and noninflammatory disorders and 50 healthy participants served as controls.</p><p><strong>Results: </strong>Thirteen patients with ROHHAD syndrome were identified. Of these, we had paired serum/CSF samples from 6 patients and only serum from the other 7. Five of 6 patients (83.3%) with paired serum/CSF (4 children, 1 adult) had ZSCAN-abs only in CSF and 1 had antibodies in serum and CSF. ZSCAN1-abs were not detected in the remaining 7 patients with ROHHAD with only serum available or in any of the 199 control samples.</p><p><strong>Discussion: </strong>Patients with ROHHAD syndrome should be investigated for the presence of ZSCAN1-abs in CSF. The antibodies do not necessarily predict the presence of a tumor. The detection of ZSCAN1-abs in an adult patient suggests that this condition also occurs beyond the pediatric age.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"11 5","pages":"e200276"},"PeriodicalIF":7.8,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11204383/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141451059","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":"Presentation and Outcome in S1P-RM and Natalizumab-Associated Progressive Multifocal Leukoencephalopathy: A Multicenter Cohort Study.","authors":"Julie C Blant, Nicola N De Rossi, Ralf Gold, Aude Maurousset, Markus Kraemer, Lucía Romero-Pinel, Tatsuro Misu, Jean-Christophe Ouallet, Maud Pallix Guyot, Simonetta Gerevini, Christos Bakirtzis, Raquel Piñar Morales, Benjamin Vlad, Panajotis Karypidis, Xavier Moisset, Tobias J Derfuss, Ilijas Jelcic, Guillaume Martin-Blondel, Ilya Ayzenberg, Corey McGraw, David A Laplaud, Renaud A Du Pasquier, Raphael Bernard-Valnet","doi":"10.1212/NXI.0000000000200281","DOIUrl":"10.1212/NXI.0000000000200281","url":null,"abstract":"<p><strong>Background and objectives: </strong>Progressive multifocal leukoencephalopathy (PML) is a severe neurologic disease resulting from JC virus reactivation in immunocompromised patients. Certain multiple sclerosis (MS) disease-modifying therapies (DMTs) are associated with PML risk, such as natalizumab and, more rarely, sphingosine-1-phosphate receptor modulators (S1P-RMs). Although natalizumab-associated PML is well documented, information on S1P-RM-associated PML is limited. The aim of this study is to compare clinical presentations and outcomes between the 2 groups.</p><p><strong>Methods: </strong>A retrospective multicenter cohort study included patients with PML from 2009 to 2022 treated with S1P-RMs or natalizumab. Data on clinical and radiologic presentation, outcomes, immune reconstitution inflammatory syndrome (IRIS), survival, disability (using the modified Ranking scale-mRS), and MS relapses post-PML were analyzed.</p><p><strong>Results: </strong>Of 88 patients, 84 were analyzed (20 S1P-RM, 64 natalizumab). S1P-RM-associated PML was diagnosed in older patients (median age 52 vs 44 years, <i>p</i> < 0.001) and after longer treatment duration (median 63.9 vs 40 months, <i>p</i> < 0.001). Similarly, S1P-RM patients were more prone to show symptoms at diagnosis (100 vs 80.6%, <i>p</i> = 0.035), had more disseminated lesions (80% vs 34.9%, <i>p</i> = 0.002), and had higher gadolinium enhancement (65% vs 39.1%, <i>p</i> = 0.042). Natalizumab patients had a higher IRIS development rate (OR: 8.3 [1.92-33.3]). Overall, the outcome (mRS) at 12 months was similar in the 2 groups (OR: 0.81 [0.32-2.0]). Yet, post-treatment MS activity was higher in S1P-RM cases (OR: 5.7 [1.4-22.2]).</p><p><strong>Discussion: </strong>S1P-RM-associated PML shows reduced IRIS risk but higher post-treatment MS activity. Clinicians should tailor post-PML treatment based on pre-PML medication.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"11 5","pages":"e200281"},"PeriodicalIF":7.8,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11256981/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141590943","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":"A 73-Year-Old Woman With Confusion, Visual Field Disturbances, and Edematous White Matter Lesions: From the National Multiple Sclerosis Society Case Conference Proceedings.","authors":"Zachery Rohm, Myla D Goldman, Claire Riley, Scott S Zamvil, Siddharama Pawate","doi":"10.1212/NXI.0000000000200300","DOIUrl":"10.1212/NXI.0000000000200300","url":null,"abstract":"<p><p>We describe the case of a 73-year-old woman presenting with headaches, confusion, and vision disturbances. Brain MRI showed a large T2-hyperintense lesion in the right temporo-occipital region with vasogenic edema and leptomeningeal enhancement. A leptomeningeal biopsy was performed, which led to a definitive diagnosis.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"11 5","pages":"e200300"},"PeriodicalIF":7.8,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11379432/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141982916","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":"CD19-Directed CAR T-Cells in a Patient With Refractory MOGAD: Clinical and Immunologic Follow-Up for 1 Year.","authors":"Jose Maria Cabrera-Maqueda, Maria Sepulveda, Raquel Ruiz García, Guillermo Muñoz-Sánchez, Nuria Martínez-Cibrian, Valentín Ortíz-Maldonado, Daniel Lorca-Arce, Mar Guasp, Sara Llufriu, Eugenia Martinez-Hernandez, Thais Armangue, Elianet G Fonseca, María Teresa Alba-Isasi, Julio Delgado, Josep Dalmau, Manel Juan, Albert Saiz, Yolanda Blanco","doi":"10.1212/NXI.0000000000200292","DOIUrl":"10.1212/NXI.0000000000200292","url":null,"abstract":"<p><strong>Objectives: </strong>In MOG antibody-associated disease (MOGAD), relapse prevention and the treatment approach to refractory symptoms are unknown. We report a patient with refractory MOGAD treated with CD19-directed CAR T-cells.</p><p><strong>Methods: </strong>CD19-directed CAR T-cells (ARI-0001) were produced in-house by lentiviral transduction of autologous fresh leukapheresis and infused after a conventional lymphodepleting regimen.</p><p><strong>Results: </strong>A 18-year-old man developed 2 episodes of myelitis associated with serum MOG-IgG, which were followed by 6 episodes of left optic neuritis (ON) and sustained the presence of MOG-IgG over 6 years despite multiple immunotherapies. After the sixth episode of ON, accompanied by severe residual visual deficits, CAR T-cell treatment was provided without complications. Follow-up of cell counts showed complete depletion of CD19⁺ B cells at day +7; reconstituted B cells at day +141 showing a naïve B-cell phenotype, and low or absent memory B cells and plasmablasts for 1 year. MOG-IgG titers have remained undetectable since CAR T-cell infusion. The patient had an early episode of left ON at day +29, when MOG-IgG was already negative, and since then he has remained free of relapses without immunotherapy for 1 year.</p><p><strong>Discussion: </strong>This clinical case shows that CD19-directed CAR T-cell therapy is well-tolerated and is a potential treatment for patients with refractory MOGAD.</p><p><strong>Classification of evidence: </strong>This provides Class IV evidence. It is a single observational study without controls.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"11 5","pages":"e200292"},"PeriodicalIF":7.8,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11309560/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141897936","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":"Should We Measure CSF Complement Levels in Patients With MOGAD?","authors":"Carson E Moseley, Scott S Zamvil","doi":"10.1212/NXI.0000000000200302","DOIUrl":"10.1212/NXI.0000000000200302","url":null,"abstract":"","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"11 5","pages":"e200302"},"PeriodicalIF":7.8,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11379433/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141971546","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":"High NEDA and No PIRA in Natalizumab-Treated Patients With Pediatric-Onset Multiple Sclerosis.","authors":"Marco Puthenparampil, Marta Gaggiola, Marta Ponzano, Giovanni Zanotelli, Alessandro Miscioscia, Margherita Nosadini, Alessandro Di Paola, Stefano Sartori, Paola Perini, Francesca Rinaldi, Francesca Bovis, Paolo Gallo","doi":"10.1212/NXI.0000000000200303","DOIUrl":"10.1212/NXI.0000000000200303","url":null,"abstract":"<p><strong>Background and objectives: </strong>Although pediatric-onset multiple sclerosis (POMS) is characterized by a more rapid accumulation of CNS inflammation than adult-onset MS (AOMS), the therapeutic algorithms applied in POMS are usually based on AOMS therapeutic outcomes. To define a high-efficacy treatment (HET)-based strategy to treat POMS, we designed an observational retrospective study aimed at evaluating the efficacy and safety of natalizumab (NTZ) in naïve POMS and AOMS.</p><p><strong>Methods: </strong>Starting from 160 patients, we applied a 2:1 (adult:pediatric) matching on propensity scores and obtained 32 patients with NTZ-treated POMS and 64 with AOMS, estimated from a multivariable logistic regression model. All patients were clinically and radiologically followed up every 6 months for a mean period of 46.0 ± 26.9 months.</p><p><strong>Results: </strong>Following re-baseline at month 6, no difference (log-rank test: <i>p</i> = 0.924) in new and enlarging T2 white matter lesions, postcontrast T1 lesions, and relapse rate were observed between POMS and AOMS throughout the study. Progression independent of relapse activity (PIRA) was never observed in POMS, while 9 of 64 patients with AOMS (12.5%) had PIRA events during the follow-up (40.0 ± 25.9 months; log-rank <i>p</i> value 0.0156). JCV seroconversion rate during NTZ infusion did not differ between POMS and AOMS (log-rank test <i>p</i> = 0.3231). Finally, no serious adverse event was observed in both POMS and AOMS.</p><p><strong>Discussion: </strong>The favorable outcomes observed on clinical, especially in PIRA, and radiologic parameters strongly support the use of NTZ as a first-choice HET in POMS.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"11 5","pages":"e200303"},"PeriodicalIF":7.8,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11379434/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141982917","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":"Young-Onset Alzheimer Dementia Due to a Novel Pathogenic <i>Presenilin 1</i> Variant Initially Misdiagnosed as Autoimmune Encephalitis.","authors":"Nathalia Rossoni Ronchi, Matheus A Castro, Artur M Coutinho, Leandro T Lucato, Guilherme Diogo Silva, Sonia M Brucki, Fernando Kok, Eduardo Sturzeneker Trés, Paulo Ribeiro Nóbrega, Fernando Freua, Ricardo Nitrini, Mateus Mistieri Simabukuro","doi":"10.1212/NXI.0000000000200280","DOIUrl":"10.1212/NXI.0000000000200280","url":null,"abstract":"<p><strong>Objectives: </strong>Pathogenic variants in presenilin 1 <i>(PSEN1)</i> are related to early-onset Alzheimer disease (AD) and may occur as de novo variants. In comparison with sporadic forms, it can present with psychiatric manifestations, seizures, myoclonus, and focal presentation. Because PSEN1 can occur in young patients who lack a family history of neurologic disorders and because these symptoms are also frequent in autoimmune encephalitis (AE), diagnosis may be overlooked. Our aim was to demonstrate the challenge in diagnosing young patients with neurodegenerative diseases that simulate AE.</p><p><strong>Methods: </strong>We describe a case of a young patient with insidious progressive dementia, myoclonus, seizures, and aphasia, with no family history of dementia, along with signs suggestive of neuroinflammation on brain MRI and CSF examination.</p><p><strong>Results: </strong>She was initially misdiagnosed as having AE. Further investigation was performed, leading to the discovery of a novel and de novo pathogenic variant in PSEN1.</p><p><strong>Discussion: </strong>This case demonstrates the importance of considering PSEN1 in young patients with insidious progressive dementia with atypical clinical and neuroimaging features, even in patients without a family history of neurologic disorders. Not adhering to published criteria of possible and probable AE and overinterpretation of subtle inflammatory findings in CSF and MRI contribute to misdiagnosis.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"11 5","pages":"e200280"},"PeriodicalIF":7.8,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11271388/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141724044","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":"Individual Prognostication of Disease Activity and Disability Worsening in Multiple Sclerosis With Retinal Layer Thickness <i>z</i> Scores.","authors":"Ting-Yi Lin, Seyedamirhosein Motamedi, Susanna Asseyer, Claudia Chien, Shiv Saidha, Peter A Calabresi, Kathryn C Fitzgerald, Sara Samadzadeh, Pablo Villoslada, Sara Llufriu, Ari J Green, Jana Lizrova Preiningerova, Axel Petzold, Letizia Leocani, Elena Garcia-Martin, Celia Oreja-Guevara, Olivier Outteryck, Patrick Vermersch, Laura J Balcer, Rachel Kenney, Philipp Albrecht, Orhan Aktas, Fiona Costello, Jette Frederiksen, Antonio Uccelli, Maria Cellerino, Elliot M Frohman, Teresa C Frohman, Judith Bellmann-Strobl, Tanja Schmitz-Hübsch, Klemens Ruprecht, Alexander U Brandt, Hanna G Zimmermann, Friedemann Paul","doi":"10.1212/NXI.0000000000200269","DOIUrl":"https://doi.org/10.1212/NXI.0000000000200269","url":null,"abstract":"<p><strong>Background and objectives: </strong>Retinal optical coherence tomography (OCT) provides promising prognostic imaging biomarkers for future disease activity in multiple sclerosis (MS). However, raw OCT-derived measures have multiple dependencies, supporting the need for establishing reference values adjusted for possible confounders. The purpose of this study was to investigate the capacity for age-adjusted <i>z</i> scores of OCT-derived measures to prognosticate future disease activity and disability worsening in people with MS (PwMS).</p><p><strong>Methods: </strong>We established age-adjusted OCT reference data using generalized additive models for location, scale, and shape for peripapillary retinal nerve fiber layer (pRNFL) and ganglion cell-inner plexiform layer (GCIP) thicknesses, involving 910 and 423 healthy eyes, respectively. Next, we transformed the retinal layer thickness of PwMS from 3 published studies into age-adjusted <i>z</i> scores (pRNFL-z and GCIP-z) based on the reference data. Finally, we investigated the association of pRNFL-z or GCIP-z as predictors with future confirmed disability worsening (Expanded Disability Status Scale score increase) or disease activity (failing of the no evidence of disease activity [NEDA-3] criteria) as outcomes. Cox proportional hazards models or logistic regression analyses were applied according to the original studies. Optimal cutoffs were identified using the Akaike information criterion as well as location with the log-rank and likelihood-ratio tests.</p><p><strong>Results: </strong>In the first cohort (n = 863), 172 PwMS (24%) had disability worsening over a median observational period of 2.0 (interquartile range [IQR]:1.0-3.0) years. Low pRNFL-z (≤-2.04) were associated with an increased risk of disability worsening (adjusted hazard ratio (aHR) [95% CI] = 2.08 [1.47-2.95], <i>p =</i> 3.82e^-5). In the second cohort (n = 170), logistic regression analyses revealed that lower pRNFL-z showed a higher likelihood for disability accumulation at the two-year follow-up (reciprocal odds ratio [95% CI] = 1.51[1.06-2.15], <i>p</i> = 0.03). In the third cohort (n = 78), 46 PwMS (59%) did not maintain the NEDA-3 status over a median follow-up of 2.0 (IQR: 1.9-2.1) years. PwMS with low GCIP-z (≤-1.03) had a higher risk of showing disease activity (aHR [95% CI] = 2.14 [1.03-4.43], <i>p</i> = 0.04). Compared with raw values with arbitrary cutoffs, applying the <i>z</i> score approach with optimal cutoffs showed better performance in discrimination and calibration (higher Harrell's concordance index and lower integrated Brier score).</p><p><strong>Discussion: </strong>In conclusion, our work demonstrated reference cohort-based <i>z</i> scores that account for age, a major driver for disease progression in MS, to be a promising approach for creating OCT-derived measures useable across devices and toward individualized prognostication.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"11 5","pages":"e200269"},"PeriodicalIF":7.8,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11214150/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141469747","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retinal Changes in Double-Antibody Seronegative Neuromyelitis Optica Spectrum Disorders.","authors":"Frederike C Oertel, Hanna G Zimmermann, Seyedamirhosein Motamedi, Charlotte Bereuter, Luca Magdalena Manthey, Fereshteh Ashtari, Rahele Kafieh, Alireza Dehghani, Mohsen Pourazizi, Lekha Pandit, Anitha D'Cunha, Orhan Aktas, Philipp Albrecht, Marius Ringelstein, Elena H Martinez-Lapiscina, Bernardo F Sanchez Dalmau, Pablo Villoslada, Nasrin Asgari, Romain Marignier, Alvaro Cobo-Calvo, Letizia Leocani, Marco Pisa, Marta Radaelli, Jacqueline Palace, Adriana Roca-Fernandez, Maria Isabel S Leite, Srilakshmi Sharma, Jerome De Seze, Thomas Senger, Michael R Yeaman, Terry J Smith, Lawrence J Cook, Alexander U Brandt, Friedemann Paul","doi":"10.1212/NXI.0000000000200273","DOIUrl":"https://doi.org/10.1212/NXI.0000000000200273","url":null,"abstract":"<p><strong>Background and objectives: </strong>To systematically describe the clinical picture of double-antibody seronegative neuromyelitis optica spectrum disorders (DN-NMOSD) with specific emphasis on retinal involvement.</p><p><strong>Methods: </strong>Cross-sectional data of 25 people with DN-NMOSD (48 eyes) with and without a history of optic neuritis (ON) were included in this study along with data from 25 people with aquaporin-4 antibody seropositive neuromyelitis optica spectrum disorder (AQP4-NMOSD, 46 eyes) and from 25 healthy controls (HCs, 49 eyes) for comparison. All groups were matched for age and sex and included from the collaborative retrospective study of retinal optical coherence tomography (OCT) in neuromyelitis optica (CROCTINO). Participants underwent OCT with central postprocessing and local neurologic examination and antibody testing. Retinal neurodegeneration was quantified as peripapillary retinal nerve fiber layer thickness (pRNFL) and combined ganglion cell and inner plexiform layer thickness (GCIPL).</p><p><strong>Results: </strong>This DN-NMOSD cohort had a history of [median (inter-quartile range)] 6 (5; 9) attacks within their 5 ± 4 years since onset. Myelitis and ON were the most common attack types. In DN-NMOSD eyes after ON, pRNFL (<i>p</i> < 0.001) and GCIPL (<i>p</i> = 0.023) were thinner compared with eyes of HCs. Even after only one ON episode, DN-NMOSD eyes already had considerable neuroaxonal loss compared with HCs. In DN-NMOSD eyes without a history of ON, pRNFL (<i>p</i> = 0.027) and GCIPL (<i>p</i> = 0.022) were also reduced compared with eyes of HCs. However, there was no difference in pRNFL and GCIPL between DN-NMOSD and AQP4-NMOSD for the whole group and for subsets with a history of ON and without a history of ON-as well as between variances of retinal layer thicknesses.</p><p><strong>Discussion: </strong>DN-NMOSD is characterized by severe retinal damage after ON and attack-independent retinal neurodegeneration. Most of the damage occurs during the first ON episode, which highlights the need for better diagnostic markers in DN-NMOSD to facilitate an earlier diagnosis as well as for effective and early treatments. In this study, people with DN-NMOSD presented with homogeneous clinical and imaging findings potentially suggesting a common retinal pathology in these patients.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"11 5","pages":"e200273"},"PeriodicalIF":7.8,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11214151/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141469748","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}