Search

Background and Objectives: The complement system is known to play a role in multiple sclerosis (MS) pathogenesis. However, its contribution to disease progression remains elusive. The study investigated the role of the complement system in disability progression of patients with primary progressive MS (PPMS)., Methods: Sixty-eight patients with PPMS from 12 European MS centers were included in the study. Serum and CSF levels of a panel of complement components (CCs) were measured by multiplex enzyme-linked immunosorbent assay at a baseline time point (i.e., sampling). Mean (SD) follow-up time from baseline was 9.6 (4.8) years. Only one patient (1.5%) was treated during follow-up. Univariable and multivariable logistic regressions adjusted for age, sex, and albumin quotient were performed to assess the association between baseline CC levels and disability progression in short term (2 years), medium term (6 years), and long term (at the time of the last follow-up)., Results: In short term, CC played little or no role in disability progression. In medium term, an elevated serum C3a/C3 ratio was associated with a higher risk of disability progression (adjusted OR 2.30; 95% CI 1.17-6.03; p = 0.040). By contrast, increased CSF C1q levels were associated with a trend toward reduced risk of disability progression (adjusted OR 0.43; 95% CI 0.17-0.98; p = 0.054). Similarly, in long term, an elevated serum C3a/C3 ratio was associated with higher risk of disability progression (adjusted OR 1.81; 95% CI 1.09-3.40; p = 0.037), and increased CSF C1q levels predicted lower disability progression (adjusted OR 0.41; 95% CI 0.17-0.86; p = 0.025)., Discussion: Proteins involved in the activation of early complement cascades play a role in disability progression as risk (elevated serum C3a/C3 ratio) or protective (elevated CSF C1q) factors after 6 or more years of follow-up in patients with PPMS. The protective effects associated with C1q levels in CSF may be related to its neuroprotective and anti-inflammatory properties.

Background: Limited data exist regarding treatment response prediction to oral disease-modifying therapies (DMTs) in multiple sclerosis (MS)., Objectives: We assessed the capacity of available scoring systems to anticipate disease activity parameters in naïve relapsing-remitting MS (RRMS) patients initiating daily oral DMTs, hypothesizing that they exhibit different predictive potentials., Methods: We conducted a retrospective study and applied the Rio Score (RS), modified Rio Score (mRS), and MAGNIMS Score 12 months after DMT initiation. At 36 months, we examined their ability to predict evidence of disease activity (EDA) components and treatment failure by logistic regression analysis., Results: Notably, 218 patients (62.4% females) initiating dimethyl fumarate, teriflunomide, and fingolimod were included. At 36 months, the RS high-risk group predicted evidence of clinical activity (odds ratio (OR) 10 [2.7-36.9]) and treatment failure (OR 10.6 [3.4-32.5]) but did not predict radiological activity (OR 1.9 [0.7-5]). The mRS non-responders group did not predict EDA and treatment failure. RS, mRS, and MAGNIMS 0 categories showed significantly lower EDA and treatment failure than the remainder., Conclusion: Scoring systems present different predictive abilities for disease activity parameters at 36 months in MS patients initiating daily oral therapies, warranting further adjustments (i.e. introduction of fluid biomarkers) to depict disease activity status fully., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: A.P. has received funding travel from Roche and speaking honoraria from Novartis; he developed this project during a 2021 ECTRIMS Clinical Training Fellowship program and is currently performing an MSIF-ARSEP Fellowship program. R.C. has received consulting services and speaking honoraria from Roche, Novartis, BIIB-Colombia, Merck, Sanofi, and was funded by an ECTRIMS Clinical Training Fellowship program. C.T. is currently being funded by a Junior Leader La Caixa Fellowship; she has also received the 2021 Merck’s Award for the Investigation in Multiple Sclerosis (Spain) and a grant (PI/01860) from Instituto de Salud Carlos III, Spain; and she has also received speaker honoraria from Roche and Novartis. A.C.C. has received a grant from Instituto de Salud Carlos III, Spain; JR19/00007. P.C.M.’s yearly salary is supported by a grant from Biogen to Fundació Privada Cemcat for statistical analysis. N.B. has received travel expenses for scientific meetings and speaking honoraria from Roche, Novartis, Biogen, and Merck, and is currently being funded by ECTRIMS Fellowship. A.V.J. receives support for contracts Juan Rodes (JR16/00024) from Fondo de Investigaciones Sanitarias, Instituto de Salud Carlos III, Spain; and has received speaking honoraria and travel expenses from Novartis, Roche, Teva, Biogen, and Sanofi-Genzyme. G.A. has received speaking honoraria, compensation for consulting services or participation in advisory boards from Sanofi, Merck, Roche, and Horizon Therapeutics; travel support for scientific meetings from Novartis, Roche, and ECTRIMS; is editor for Europe of the Multiple Sclerosis Journal—Experimental, Translational and Clinical; is a member of the International Women in Multiple Sclerosis (iWiMS) network executive committee; and is a member of the European Biomarkers in MS (BioMS-eu) consortium steering committee. N.M.O. has a predoctoral grant Rio Hortega, from the Instituto de Salud Carlos III (Spain). C.N. has received funding for travel from Biogen Idec and F. Hoffmann-La Roche, and speaker honoraria from Novartis. B.R.A. has received honoraria for consulting services from Wellspect. A.Z. has received travel expenses for scientific meetings from Biogen Idec, Merck Serono, and Novartis; speaking honoraria from Eisai; and a study grant from Novartis. M.C. has received compensation for consulting services and speaking honoraria from Bayer Schering Pharma, Merck Serono, Biogen Idec, Teva Pharmaceuticals, Sanofi-Aventis, and Novartis. J.S.G. has received compensation for participating on Advisory Boards, speaking honoraria, and travel expenses for scientific meetings, consulting services, or research support from Celgene, Novartis, Biogen, Teva, Merck, Almirall, and Genzyme. M.T. has received compensation for consulting services, speaking honoraria from Almirall, Bayer Schering Pharma, Biogen Idec, Genzyme, Merck Serono, Novartis, Roche, Sanofi Aventis, and Teva Pharmaceuticals, and is co-editor of Multiple Sclerosis Journal—ETC. A.R. serves on scientific advisory boards for Novartis, Sanofi Genzyme, Icometrix, SyntheticMR, Bayer, Biogen, and OLEA Medical, and has received speaker honoraria from Bayer, Sanofi Genzyme, Bracco, Merck Serono, Teva Pharmaceutical Industries Ltd., Novartis, Roche, and Biogen. X.M. has received speaking honoraria and travel expenses for participation in scientific meetings, has been a steering committee member of clinical trials or participated in advisory boards of clinical trials in the past years with Abbvie, Actelion, Alexion, Biogen, Bristol Myers Squibb/Celgene, EMD Serono, Genzyme, Hoffmann-La Roche, Immunic, Janssen Pharmaceuticals, MedDay, Merck, Mylan, NervGen, Novartis, Sandoz, Sanofi Genzyme, Teva Pharmaceutical, TG Therapeutics, Excemed, MSIF, and NMSS. J.R. has received speaking honoraria and personal compensation for participating on Advisory Boards from Almirall, Bayer Schering Healthcare, Biogen Idec, Genzyme, Merck Serono, Novartis, Teva, and Sanofi Aventis. C.A., A.S.A., J.C.J., L.B., L.M., A.S., I.G., and M.R.B. report no disclosures.

Background: We aimed to investigate the potential of serum biomarker levels to predict disability progression in a multicentric real-world cohort of patients with primary progressive multiple sclerosis (PPMS)., Methods: A total of 141 patients with PPMS from 18 European MS centres were included. Disability progression was investigated using change in Expanded Disability Status Scale (EDSS) score over three time intervals: baseline to 2 years, 6 years and to the last follow-up. Serum levels of neurofilament light chain (sNfL), glial fibrillar acidic protein (sGFAP) and chitinase 3-like 1 (sCHI3L1) were measured using single-molecule array assays at baseline. Correlations between biomarker levels, and between biomarkers and age were quantified using Spearman's r. Univariable and multivariable linear models were performed to assess associations between biomarker levels and EDSS change over the different time periods., Results: Median (IQR) age of patients was 52.9 (46.4-58.5) years, and 58 (41.1%) were men. Median follow-up time was 9.1 (7.0-12.6) years. Only 8 (5.7%) patients received treatment during follow-up. sNfL and sGFAP levels were moderately correlated (r=0.43) and both weakly correlated with sCHI3L1 levels (r=0.19 and r=0.17, respectively). In multivariable analyses, levels of the three biomarkers were associated with EDSS changes across all time periods. However, when analysis was restricted to non-inflammatory patients according to clinical and radiological parameters (n=64), only sCHI3L1 levels remained associated with future EDSS change., Conclusions: Levels of sNfL, sGFAP and sCHI3L1 are prognostic biomarkers associated with disability progression in patients with PPMS, being CHI3L1 findings less dependent on the inflammatory component associated with disease progression., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Objectives: We aimed to assess the presence of retinal neurodegeneration independent of optic neuritis (ON) in myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) and to investigate the development of trans-synaptic anterograde degeneration in these patients after ON., Methods: Cross-sectional, retrospective study of 34 adult patients with MOGAD and 23 healthy controls (HC). Clinical, optical coherence tomography (OCT), and MRI data were collected. Peripapillary retinal nerve fiber layer (pRNFL) and ganglion cell inner plexiform layer (GCIPL) were obtained using Heidelberg Spectralis. FreeSurfer7 was used to obtain the lateral geniculate nucleus (LGN), occipital volume fractions (to total estimated intracranial volume), and occipital cortical thickness. For the anterior visual pathway, the analysis was conducted using eyes, classified based on the history of ON (Eye-ON and Eye-NON) and compared with Eye-HC. The analysis of OCT and brain volumetric measures was conducted comparing MOGAD-ON, MOGAD-NON, and HC groups. The analysis of covariance with a Bonferroni-adjusted post hoc test was used to test differences between groups and linear regression analysis to evaluate OCT/MRI associations; age and sex were considered as covariates., Results: 24 (70.5%) patients had a prior ON. Median pRNFL and GCIPL thickness (um) was significantly reduced in Eye-ON vs EyeNON and HC (pRNFL: 69.4 (17.3), 89.6 (13.7), 98.2 (11.7), p < 0.001; GCIPL: 55.8 (8.7), 67.39 (8.7), 72.6 (4.5), p < 0.001). pRNFL and GCIPL thickness had a negative correlation with the number of ON episodes ( p = 0.025 and p = 0.031, respectively). LGN volume fraction was significantly lower in patients with MOGAD-ON than in HC (0.33 (0.05) vs 0.39 (0.04), p = 0.002). The occipital cortical thickness was lower in MOGAD-ON compared with MOGAD-NON and HC ( p = 0.010). In patients with MOGAD-ON, pRNFL correlated with LGN volume ( p = 0.006), occipital thickness ( p = 0.002), and the medial occipital cortex ( p = 0.002), but not the lateral occipital lobe., Discussion: Compared with HC, MOGAD-ON exhibits reduced retinal thickness, primarily influenced by the presence and the number of prior ON episodes. Moreover, MOGAD-ON demonstrates significant atrophy in the retinal, subcortical, and cortical regions of the visual pathway, distinguishing them from MOGAD-NON and HC. These findings suggest that in patients with MOGAD neurodegeneration is tightly correlated with damage to the involved pathway.

Importance: Vaccination in patients with highly active multiple sclerosis (MS) requiring prompt treatment initiation may result in impaired vaccine responses and/or treatment delay., Objective: To assess the immunogenicity and safety of inactivated vaccines administered during natalizumab treatment., Design, Setting, and Participants: This self-controlled, prospective cohort study followed adult patients with MS from 1 study center in Spain from September 2016 to February 2022. Eligible participants included adults with MS who completed immunization for hepatitis B virus (HBV), hepatitis A virus (HAV), and COVID-19 during natalizumab therapy. Data analysis was conducted from November 2022 to February 2023., Exposures: Patients were categorized according to their time receiving natalizumab treatment at the time of vaccine administration as short-term (≤1 year) or long-term (>1 year)., Main Outcomes and Measures: Demographic, clinical, and radiological characteristics were collected during the year before vaccination (prevaccination period) and the year after vaccination (postvaccination period). Seroprotection rates and postvaccination immunoglobulin G titers were determined for each vaccine within both periods. Additionally, differences in annualized relapse rate (ARR), new T2 lesions (NT2L), Expanded Disability Status Scale (EDSS) scores, and John Cunningham virus (JCV) serostatus between the 2 periods were assessed., Results: Sixty patients with MS (mean [SD] age, 43.2 [9.4] years; 44 female [73.3%]; 16 male [26.7%]; mean [SD] disease duration, 17.0 [8.7] years) completed HBV, HAV, and mRNA COVID-19 immunization during natalizumab treatment, with 12 patients in the short-term group and 48 patients in the long-term group. The global seroprotection rate was 93% (95% CI, 86%-98%), with individual vaccine rates of 92% for HAV (95% CI, 73%-99%), 93% for HBV (95% CI, 76%-99%), and 100% for the COVID-19 messenger RNA vaccine (95% CI, 84%-100%). Between the prevaccination and postvaccination periods there was a significant reduction in the mean (SD) ARR (0.28 [0.66] vs 0.01 [0.12]; P = .004) and median (IQR) NT2L (5.00 [2.00-10.00] vs 0.81 [0.00-0.50]; P = .01). No changes in disability accumulation were detected (median [IQR] EDSS score 3.5 [2.0-6.0] vs 3.5 [2.0-6.0]; P = .62). No differences in safety and immunogenicity were observed for all vaccines concerning the duration of natalizumab treatment., Conclusions and Relevance: The findings of this cohort study suggest that immunization with inactivated vaccines during natalizumab therapy was both safe and immunogenic, regardless of the treatment duration. Natalizumab may be a valuable option for proper immunization, averting treatment delays in patients with highly active MS; however, this strategy needs to be formally evaluated.

Purpose: The optic chiasm (OC) is a central structure in the visual pathway and can be visualized in conventional MRI, but no consensus regarding its measurement has been defined. We aim to investigate the most reproducible manual approach to OC measurement and to explore associations of OC with optical coherence tomography (OCT) parameters, and automatic brain segmentation (FreeSurfer) in subacute optic neuritis (sON), multiple sclerosis without optic neuritis (MSwoON), and healthy subjects (HS)., Materials and Methods: We reproduced two previously reported methodologies and implemented a new proposed simplified approach, entitled optic chiasm mean area (OCMA). The intra and inter-rater reliability and reproducibility were assessed through the intraclass correlation (ICC) and Dice similarity (DSC) coefficients. Partial correlations were calculated to gauge the associations between OCMA fraction (OCMA divided by total intracranial volume), brain regional segmentations derived from FreeSurfer, and OCT parameters., Results: We have analysed 43 sON, 20 MSwoON, and 20 HS. OCMA presented better results for reliability in both intra- and inter-rater analysis (excellent ICC and DSC with over 80% overlap between masks), as compared to the other two approaches. OCMA fraction was associated with OC volume fraction obtained with Freesurfer in all groups, brain parenchymal fraction, and OCT parameters in MSwoON., Conclusions: The OCMA is a simplified approach to measure OC atrophy, has a higher reliability than the current approaches and shows association with an automated method. OC-derived measures seem to reflect diffuse neurodegenerative damage, whereas, in patients with subacute ON, it may be associated with local damage., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: NB: has received a Fellowship grant from the European Committee for Treatment and Research in Multiple Sclerosis. DP: has received a research grant from Biogen Idec and a from Fondo de Investigación Sanitaria (PI18/00823, PI22/01709), co-funded by the European Union. NM-O: has a predoctoral grant Rio Hortega, from the Instituto de Salud Carlos III (CM21/00018). BR - A: has received speaking honoraria from Merck and honoraria for consulting services from Novartis. CA: has nothing to disclose. MA: has nothing to disclose. SC: has nothing to disclose. AV-J: has received support for contracts Juan Rodes (JR16/00024) and from Fondo de Investigación en Salud (PI17/02162 and PI22/01589) from Instituto de Salud Carlos III, Spain, and has engaged in consulting and/or participated as a speaker in events organized by Roche, Novartis, Merck, and Sanofi. MT: has received compensation for consulting services, speaking honoraria, and research support from Almirall, Bayer Schering Pharma, Biogen-Idec, Genzyme, Janssen, Merck-Serono, Novartis, Roche, Sanofi-Aventis, Viela Bio, and Teva Pharmaceuticals. XM: has received speaking honoraria and travel expenses for participation in scientific meetings, has been a steering committee member of clinical trials or participated in advisory boards of clinical trials in the past years with Abbvie, Actelion, Alexion, Biogen, Bristol-Myers Squibb/Celgene, EMD Serono, Genzyme, Hoffmann-La Roche, Immunic, Janssen Pharmaceuticals, Medday, Merck, Mylan, Nervgen, Novartis, Sandoz, Sanofi-Genzyme, Teva Pharmaceutical, TG Therapeutics, Excemed, MSIF, and NMSS”. AR: serves/ed on scientific advisory boards for Novartis, Sanofi-Genzyme, SyntheticMR, TensorMedical, Roche, Biogen, and OLEA Medical, and has received speaker honoraria from Bayer, Sanofi-Genzyme, Merck-Serono, Teva Pharmaceutical Industries Ltd, Novartis, Roche, Bristol-Myers, and Biogen. JS-G: serves as co-editor for Europe for the Multiple Sclerosis Journal and as Editor-in-Chief of Revista de Neurología, receives research support from Fondo de Investigaciones Sanitarias (19/950 and 22/750) and has served as a consultant/speaker for Biogen, Celgene/Bristol Meyers Squibb, Sanofi, Novartis, and Merck., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Mumps-Measles-Rubella (MMR) and Varicella zoster vaccines (VAR) are live attenuated vaccines, usually administered in a two-dose scheme at least 4 weeks apart. However, single-dose immunization schemes may also be effective and can reduce delays in immunosuppressive treatment initiation in patients with multiple sclerosis (pwMS) who need to be immunized., Objectives: To evaluate the immunogenicity of a single-dose attempt (SDA) versus the standard immunization scheme (SIS) with VAR and/or MMR in pwMS., Methods: Retrospective observational study in pwMS vaccinated against VAR and/or MMR. We compared seroprotection rates and antibody geometric mean titers (GMTs) between the two strategies., Results: Ninety-six patients were included. Thirty-one patients received VAR and 67 MMR. In the SDA group, the seroprotection rate was 66.7% (95% confidence interval (CI): 53.3-78.3) versus 97.2% (95% CI: 85.5-99.9) in the SIS ( p  < 0.001). For the seroprotected patients, GMTs were similar for both schemes., Conclusion: An SDA of VAR and/or MMR vaccines could be sufficient to protect almost two-thirds of patients. Testing immunogenicity after a single dose of VZ and/or MMR could be included in routine clinical practice to achieve rapid immunization., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: R. Carvajal is currently being funded by ‘Vall d’Hebron Institut de Recerca’ grand, this project was supported by ECTRIMS Fellowship training performed during 2021–2022, he has also received speaking honoraria and personal compensation for participating on Advisory Boards and from Roche, Novartis, BIIB-Colombia, Merck, and Sanofi. C. Tur is currently being funded by a Junior Leader La Caixa Fellowship (fellowship code is LCF/BQ/PI20/11760008), awarded by ‘la Caixa’ Foundation (ID 100010434), she has also received the 2021 Merck’s Award for the Investigation in MS, awarded by Fundación Merck Salud (Spain) and a grant awarded by the Instituto de Salud Carlos III (ISCIII), Ministerio de Ciencia e Innovación de España (PI21/01860); in 2015, she received an ECTRIMS Post-doctoral Research Fellowship and has received funding from the UK MS Society, she is a member of the Editorial Board of Neurology and Multiple Sclerosis Journal, she has also received honoraria from Roche and Novartis and is a steering committee member of the O’HAND trial and of the Consensus group. X. Martínez-Gómez has received research support fees from GlaxoSmithKline, Sanofi Pasteur MSD, Statens Serum Institut & Janssen Vaccine, as well as travel expenses fees from GlaxoSmithKline and Sanofi Pasteur MS. L. Bollo is supported by a 1-year stipend endowed by the NMSS/AAN John Dystel Prize for Multiple Sclerosis Research awarded to Prof. Xavier Montalban in 2022. J. Esperalba reports no disclosures. M. Rodríguez reports no disclosures. A. Pappolla has received funding travel from Roche and speaking honoraria from Novartis. He developed this project during a 2021 ECTRIMS Clinical Training Fellowship programme, and is currently performing an MSIF-ARSEP Fellowship programme. A. Cobo-Calvo has received a grant from Instituto de Salud Carlos III, Spain; JR19/00007. P. Carbonell yearly salary is supported by a grant from Biogen to Fundació privada Cemcat for statistical analysis. B. Borras-Bermejo has received travel expenses for scientific meetings from GlaxoSmithKline J. Rio has received speaking honoraria and personal compensation for participating on Advisory Boards from Biogen-Idec, Genzyme, Janssen, Merck-Serono, Novartis, Teva, Roche, and Sanofi-Aventis. J. Castilló reports no disclosures. N. Braga has received travel expenses for scientific meetings and speaking honoraria from Roche, Novartis, Biogen, Merck and was funded by ECTRIMS Fellowship in 2022–2023. N. Mongay-Ochoa has a predoctoral grant Rio Hortega, from the Instituto de Salud Carlos III (CM21/00018), she also has received speaking honoraria and travel expenses from Merck and Roche. J.A. Rodigo-Pendás has received research support fees from GlaxoSmithKline, Sanofi Pasteur MSD, Statens Serum Institut, Janssen Vaccines & Prevention B.V. and Spanish Clinical Research Network—SCReN and travel expenses fees from Sanofi Pasteur MSD. A. Vidal-Jordana has engaged in consulting and/or participated as speaker in events organized by Roche, Novartis, Merck, and Sanofi. G. Arrambide has received speaking honoraria and consulting services or participation in advisory boards from Sanofi, Merck, Roche, and Horizon Therapeutics; travel expenses for scientific meetings from Novartis, Roche, and ECTRIMS. I. Galán reports no disclosures. B. Rodríguez-Acevedo has received speaking honoraria from Merck and honoraria for consulting services from Novartis. A. Zabalza has a predoctoral grant Rio Hortega, from the Instituto de Salud Carlos III, Spain (CM22/00237), received travel expenses for scientific meetings from Biogen-Idec, Merck Serono and Novartis, speaking honoraria from Eisai and a study grant from Novartis. L. Midaglia reports no disclosures. M. Comabella has received compensation for consulting services and speaking honoraria from Bayer Schering Pharma, Merck Serono, Biogen-Idec, Teva Pharmaceuticals, Sanofi-Aventis, Genzyme, and Novartis. J. Sastre-Garriga serves as co-Editor for Europe on the editorial board of Multiple Sclerosis Journal and as Editor-in-Chief in Revista de Neurología, receives research support from Fondo de Investigaciones Sanitarias (19/950) and has served as a consultant/speaker for Biogen, Celgene/Bristol Meyers Squibb, Sanofi, Novartis and Merck. X. Montalbán has received speaking honoraria and travel expenses for participation in scientific meetings, has been a steering committee member of clinical trials or participated in advisory boards of clinical trials in the past years with Abbvie, Actelion, Alexion, Biogen, Bristol-Myers Squibb/Celgene, EMD Serono, Genzyme, Hoffmann-La Roche, Immunic, Janssen Pharmaceuticals, Medday, Merck, Mylan, Nervgen, Novartis, Sandoz, Sanofi-Genzyme, Teva Pharmaceutical, TG Therapeutics, Excemed, MSIF, and NMSS. M. Tintore has received compensation for consulting services, speaking honoraria and research support from Almirall, Bayer Schering Pharma, Biogen-Idec, Genzyme, Janssen, Merck-Serono, Novartis, Roche, Sanofi-Aventis, Viela Bio and Teva Pharmaceuticals. Data Safety Monitoring Board for Parexel and UCB Biopharma. S. Otero-Romero has received speaking and consulting honoraria from Genzyme, Biogen-Idec, Novartis, Roche, Excemed, and MSD; as well as research support from Novartis.

Objective: Myelin oligodendrocyte glycoprotein antibodies (MOG-Ab) distinguish multiple sclerosis (MS) from MOG-associated disease in most cases. However, studies analyzing MOG-Ab at the time of a first demyelinating event suggestive of MS in adults are lacking. We aimed to (1) evaluate the prevalence of MOG-Ab in a first demyelinating event suggestive of MS and (2) compare clinical and paraclinical features between seropositive (MOG-Ab+) and seronegative (MOG-Ab-) patients., Methods: Six hundred thirty adult patients with available serum samples obtained within 6 months from the first event were included. MOG-Ab were analyzed using a live cell-based assay. Statistical analyses included parametric and nonparametric tests, logistic regression, and survival models., Results: MOG-Ab were positive in 17 of 630 (2.7%). Fourteen out of 17 (82.4%) MOG-Ab+ patients presented with optic neuritis (ON) compared to 227of 613 (37.0%) MOG-Ab- patients (p = 0.009). Cerebrospinal fluid-restricted oligoclonal bands (CSF-OBs) were found in 2 of 16 (12.5%) MOG-Ab+ versus 371 of 601 (61.7%) MOG-Ab- subjects (p < 0.001). Baseline brain magnetic resonance imaging (MRI) was normal in 9 of 17 (52.9%) MOG-Ab+ versus 153 of 585 (26.2%) MOG-Ab- patients (p = 0.029). Absence of CSF-OBs and ON at onset were independently associated with MOG-Ab positivity (odds ratio [OR] = 9.03, 95% confidence interval [CI] = 2.04-53.6, p = 0.009; and OR = 4.17, 95% CI = 1.15-19.8, p = 0.042, respectively). Of MOG-Ab+ patients, 22.9% (95% CI = 0.0-42.7) compared to 67.6% (95% CI = 63.3-71.3) of MOG-Ab- patients fulfilled McDonald 2017 criteria at 5 years (log-rank p = 0.003)., Interpretation: MOG-Ab are infrequent in adults with a first demyelinating event suggestive of MS. However, based on our results, we suggest to determine these antibodies in those patients with ON and absence of CSF-OBs, as long as the brain MRI is not suggestive of MS. ANN NEUROL 2023., (© 2023 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Introduction: On 4 and 5 November 2022, Madrid hosted the 15th edition of the Post-ECTRIMS Meeting, where neurologists specialised in multiple sclerosis outlined the latest developments presented at the 2022 ECTRIMS Congress, held in Amsterdam from 26 to 28 October., Aim: To synthesise the content presented at the 15th edition of the Post-ECTRIMS Meeting, in an article broken down into two parts., Development: This second part describes the new developments in terms of therapeutic strategies for escalation and de-escalation of disease-modifying therapies (DMT), when and in whom to initiate or switch to highly effective DMT, the definition of therapeutic failure, the possibility of treating radiologically isolated syndrome and the future of personalised treatment and precision medicine. It also considers the efficacy and safety of autologous haematopoietic stem cell transplantation, different approaches in clinical trial design and outcome measures to assess DMT in progressive stages, challenges in the diagnosis and treatment of cognitive impairment, and treatment in special situations (pregnancy, comorbidity and the elderly). In addition, results from some of the latest studies with oral cladribine and evobrutinib presented at ECTRIMS 2022 are shown.

Background and Purpose: As in the brain reserve concept, a larger cervical canal area may also protect against disability. In this context, a semiautomated pipeline has been developed to obtain quantitative estimations of the cervical canal area. The aim of the study was to validate the pipeline, to evaluate the consistency of the cervical canal area measurements during a 1-year period, and to compare cervical canal area estimations obtained from brain and cervical MRI acquisitions., Materials and Methods: Eight healthy controls and 18 patients with MS underwent baseline and follow-up 3T brain and cervical spine sagittal 3D MPRAGE. The cervical canal area was measured in all acquisitions, and estimations obtained with the proposed pipeline were compared with manual segmentations performed by 1 evaluator using the Dice similarity coefficient. The cervical canal area estimations obtained on baseline and follow-up T1WI were compared; brain and cervical cord acquisitions were also compared using the individual and average intraclass correlation coefficients., Results: The agreement between the manual cervical canal area masks and the masks provided by the proposed pipeline was excellent, with a mean Dice similarity coefficient mean of 0.90 (range, 0.73-0.97). The cervical canal area estimations obtained from baseline and follow-up scans showed a good level of concordance (intraclass correlation coefficient = 0.76; 95% CI, 0.44-0.88); estimations obtained from brain and cervical MRIs also had good agreement (intraclass correlation coefficient = 0.77; 95% CI, 0.45-0.90)., Conclusions: The proposed pipeline is a reliable tool to estimate the cervical canal area. The cervical canal area is a stable measure across time; moreover, when cervical sequences are not available, the cervical canal area could be estimated using brain T1WI., (© 2023 by American Journal of Neuroradiology.)

Background: Dysphagia is a common symptom in multiple sclerosis that can occur even early in the disease course and can lead to serious complications. Early recognition and treatment can promote comfort, safety and optimal nutritional status. Few dysphagia rating scales are available in Spanish. The aim of this study was to translate the Dysphagia in Multiple Sclerosis Questionnaire (DYMUS) into Spanish and to validate it., Methods: Forward and backward translation method was used to translate the original English version of DYMUS into Spanish. A pilot-study with 10 PwMS was carried on in order to improve the intelligibility of the instrument, comprehensibility and content validity of the questionnaire. The questionnaire was filled out by 100 PwMS who were asked a dichotomous question on their swallowing ("Do you have swallowing troubles?"). Descriptive data are presented as median and quartiles for continuous variables and frequency and percentage for categorical ones. Internal consistency reliability was estimated by Cronbach's alfa. Test-retest reliability was estimated by intraclass correlation coefficient. Concurrent validity with a speech and language therapy assessment (SLT-A) was measured with the weighted kappa statistic for the concordance for both dysphagia type and degree categories. Confirmatory factor analysis by means of structural equation models was used to verify the two-factor (solids and liquids) structure of the DYMUS questionnaire. As the goodness of fit evaluation was poor, an additional exploratory factor analysis was carried out., Results: Internal consistency was high. The globus sensation question and the weight loss questions (item 3 and 10) are the least specific with dysphagia symptomatology so they are worst correlated with the sum of the others (item-rest correlation, 0.243 and 0.248, respectively). The test-retest reliability of the DYMUS among 40 patients using ICC was 0.75 (95% CI 0.57 - 0.86). Concurrent validity with SLT-A was poor (weighted kappa 0.37 for dysphagia type and 0.38 for dysphagia degree). The DYMUS questionnaire detected three times more dysphagia (53% versus 17%) than the dichotomous question. Confirmatory factors analysis failed to confirm the bidimensional structure (solid and liquid items) often reported in other validation studies. The subsequent exploratory factor analysis also identified two factors, but with poor interpretability., Conclusion: DYMUS-SP scale is not a sufficiently useful scale to detect dysphagia in PwMS due to the poor concurrent validity and the probable overdiagnosis of the condition; however, it can be helpful as a screening tool when combined with other measures., Competing Interests: Declaration of Competing Interest Mar Tintoré has received compensation for consulting services, speaking honoraria and research support from Almirall, Bayer Schering Pharma, Biogen-Idec, Genzyme, Janssen, Merck-Serono, Novartis, Roche, Sanofi-Aventis, Viela Bio and Teva Pharmaceuticals. Data Safety Monitoring Board for Parexel and UCB Biopharma, (Copyright © 2023. Published by Elsevier B.V.)

Background and Purpose: Glutamic acid decarboxylase antibodies (GAD-Ab) are sometimes associated with chronic drug-resistant focal epilepsy. Clinically, it may manifest as mesial temporal lobe epilepsy (mTLE), with GAD-Ab patients difficult to distinguish. Therefore, the aim of this study is to compare brain metabolism of patients with mTLE and high serum titers of GAD-Ab (>2000 UI/ml) to those with mTLE and hippocampal sclerosis (HS) and confirmed GAD-ab negativity., Methods: Images from PET studies were normalized to an SPM 12 template. Voxel to voxel comparisons were made using a two-sample one-tailed t-test., Results: In both patients with GAD-Ab and controls (mTLE-HS), hypometabolism in mesial temporal lobe areas was observed. When comparing the two groups, GAD-Ab patients had statistically significant reduced metabolism in both insulae and medial inferior frontal-hypothalamus area (p < 0.001)., Conclusions: Hypometabolism in mesial temporal lobe areas together with hypometabolism in insulae and medial inferior frontal-hypothalamus may be characteristic of patients with epilepsy and GAD-ab. This PET pattern could be a useful diagnostic tool to identify GAD-Ab patients., (© 2021 American Society of Neuroimaging.)