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BackgroundTreatment and monitoring decisions in people with multiple sclerosis (MS) are based commonly on clinician-reported outcomes. These reflect physical and radiological disease activity and are the most relevant endpoints in clinical trials. Over the past few years, the number of studies evaluating so-called patient-reported outcomes (PROs) has been increasing. PROs are reports from patients concerning their own health perception. They are typically obtained by means of questionnaires and aim to quantify symptoms such as fatigue, depression, and sexual dysfunction. The emergence of PROs has made a tremendous contribution to understanding the individual impact of disease in people with MS and their health-related quality of life. However, the assessment of PROs consumes resources, including time and personnel. Thus, useful ways to conveniently introduce PROs into clinical practice are needed. ObjectiveWe aim to provide a rationale and pilot study protocol for a mobile health (mHealth) solution named “haMSter” that allows for remote monitoring of PROs in people with MS. MethodsThe core function of haMSter is to provide three scientifically validated PRO questionnaires relevant to MS for patients to fill out at home once a month. Thereby, longitudinal and remote documentation of PROs is enabled. A scoring algorithm graphically plots PRO scores over time and makes them available at the next visit. ResultsThe pilot study is currently ongoing and will evaluate adherence to this mHealth solution in 50 patients over a period of 6 months. Results from the haMSter pilot study are expected in 2021. ConclusionshaMSter is a novel mHealth-based solution for modern PRO research, which may constitute the first step in achieving the ability to integrate PROs in clinical practice. This allows for a more problem-oriented approach in monitoring visits, which addresses patient needs and ultimately saves time. Trial RegistrationClinicalTrials.gov NCT04555863; https://clinicaltrials.gov/ct2/show/NCT04555863 International Registered Report Identifier (IRRID)DERR1-10.2196/25011

Background: Paramagnetic rim lesions (PRLs) are chronic active lesions associated with a more severe disease course in multiple sclerosis (MS). Retinal layer thinning measured by optical coherence tomography (OCT) is a biomarker of neuroaxonal damage associated with disability progression in MS. Objective: We aimed to determine a potential association between OCT parameters (peripapillary retinal nerve fiber layer (pRNFL) ganglion cell-inner plexiform layer (GCIPL), inner nuclear layer (INL) thickness), and PRLs in patients with MS (pwMS). Methods: In this cross-sectional retrospective study, we included pwMS with both 3T brain MRI and an OCT scan. Regression models were calculated with OCT parameters (pRNFL, GCIPL, INL) as dependent variables, and the number of PRLs as an independent variable adjusted for covariates. Results: We analyzed data from 107 pwMS (mean age 34.7 years (SD 10.9), 64.5% female, median disease duration 6 years (IQR 1–13), median EDSS 1.5 (range 0–6.5)). Higher number of PRLs was associated with lower pRNFL (β = −0.18; 95% CI −0.98, −0.03; p = 0.038) and GCIPL thickness (β = −0.21; 95% CI −0.58, −0.02; p = 0.039). Conclusion: The association between higher number of PRLs and lower pRNFL and GCIPL thicknesses provides additional evidence that pwMS with PRLs are affected by a more pronounced neurodegenerative process. [ABSTRACT FROM AUTHOR]

Background: Multiple sclerosis (MS) is an inflammatory and neurodegenerative disease whose aetiology is not fully understood. The female sex is clearly predominant, with a sex ratio between 2 and 3. In primary progressive MS the sex ratio almost balances out. Since the age at onset is higher for patients with progressive onset (POMS) than for relapsing onset (ROMS), it can be hypothesized that the age at onset is a decisive factor for the sex ratio. Methods: To address this aspect, we compare clinical and demographic data between females and males for the different disease courses within the population of the German MS Register by the German MS Society. Only patients with complete details in mandatory data items and a follow-up visit since 01. Jan 2018 were included.Results: A total of 18,728 patients were included in our analyses, revealing a female-to-male ratio of 2.6 (2.7 for patients with ROMS and 1.3 for POMS). The age at diagnosis is higher in patients with POMS (43.3 and 42.3 years for females and males versus 32.1 and 33.2 years, respectively). Females irrespective of disease course are statistically significantly more often affected by cognitive impairment (POMS: p = 0.013, ROMS: p = 0.001) and depression (POMS: p = 0.002, ROMS: 0.001) and suffer more often from pain (POMS and ROMS: p< 0.001). Fatigue is significantly more often seen in females with ROMS (p< 0.001) but not in POMS. Females with ROMS retire significantly (p< 0.001) earlier (42.8 versus 44.2 years) and to a greater extent than males (28 versus 24%). Disease progression was similar for women and men.Conclusion: Our analysis shows that clinical and demographic data differ more between disease courses than between men and women. For pain, depression and cognitive impairment the female sex is the decisive factor. Whether these factors are responsible for the earlier retirement of females with ROMS is not clear. Appropriate measures for optimization of symptomatic treatment as well as to promote employment should be taken. [ABSTRACT FROM AUTHOR]

Background: Multiple sclerosis (MS) is a neuroinflammatory and neurodegenerative disease. Over time, symptoms accumulate leading to increased disability of patients. Objective: The objective of this article is to analyze the prevalence of symptoms and symptomatic treatment patterns in a nationwide MS registry. Methods: Data sets from 35,755 patients were analyzed. Results: More than two-thirds of patients were women with a mean age of 46.1 (±12.8) years. Median Expanded Disability Status Score (EDSS) was 3.0. The most frequently reported symptoms were fatigue, spasticity, and voiding disorders. In patients with short disease duration, fatigue was reported most frequently. Symptomatic treatment was most common for spasticity and depression, whereas fatigue was treated only in a third of affected patients. Almost a fifth of patients with EDSS ⩽ 3.5 and neuropsychological symptoms had retired from work. Conclusion: Whereas treatment for spasticity and depression is common in our cohort, sexual dysfunction, dysphagia, cognitive dysfunction, and fatigue are treated to a far lesser extent. The need for psychological support, physical, and occupational therapy has to be recognized as neuropsychological symptoms have a great impact on retirement at an early stage. Overall symptomatic treatment rates for the most common symptoms have increased over the last years (p < 0.001). [ABSTRACT FROM AUTHOR]

Objectives: The incidence and clinical impact of serum autoantibodies in patients with multiple sclerosis (MS) are controversially discussed. The aim of the study was to reassess the value of elevated serum autoantibodies in our MS study cohort. Material & Methods: In total, 176 MS patients were retrospectively analyzed for coexistence and clinical impact of increased serum autoantibody levels. Results: The 18.8% of the MS cohort showed elevated serum autoantibody levels, but only 10.2% of all MS patients were diagnosed with a further autoimmune disease (AI). Patients with elevated serum autoantibodies (AABS) were not significantly more often diagnosed with a clinical manifest AI as compared to patients with negative autoantibodies (P = 0.338). MS patients with disease duration of more than 10 years showed no significant increase of positive autoantibodies as compared to patients with a more recent disease onset (P = 1). MS patients with elevated serum autoantibodies did not exhibit a significantly worse disease course (P = 0.428). Conclusions: According to our data, elevated serum autoantibodies do not have the potential to serve as a prognostic tool for disease severity in patients with MS Since MS patients with positive serum AABS did not significantly more often suffer from clinical manifest AIs than MS patients with negative serum AABS, the role of routine testing of serum AABS in MS patients should be critically called into question. [ABSTRACT FROM AUTHOR]

Summary: Background: Multiple sclerosis (MS) affects predominantly young women. Currently available disease‐modifying drugs have neither been approved during pregnancy nor nursing. Aims: Evaluating the effect of treatment with intravenous immunoglobulin (IVIg) in MS patients with desire to have a baby. Methods: In all, 70 MS patients were either treated with IVIg before conception, during first trimester of pregnancy and 12 months postnatal (group I, n = 38) or started IVIg after delivery for 12 months (group II, n = 23) or were untreated (group III, n = 9). Relapse rates and disease progression were analyzed. Results: Pre‐gestational relapse rates differed between groups. Lowest relapse rates were observed during late pregnancy, followed by an elevated relapse rate after delivery compared to the pre‐pregnancy year and the first trimester. Only in group I, the postnatal relapse rate did not exceed the relapse rate before conception. IVIg treatment did not influence disease progression after delivery. Conclusions: In MS patients, IVIg treatment during and/or after delivery is an option to reduce the incidence of relapses during pregnancy and the postnatal period. Surprisingly, untreated patients becoming pregnant showed an increase in the relapse rate in the first trimester compared with the pre‐gestational period. How alterations of hormone status during pregnancy affect disease activity in MS has to be further investigated. [ABSTRACT FROM AUTHOR]

Background: Incomplete attack remission is the main cause of disability in myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). Apheresis therapies such as plasma exchange and immunoadsorption are widely used in neuroimmunology. Data on apheresis outcomes in MOGAD attacks remain limited., Methods: We retrospectively evaluated all apheresis treated attacks occurring in patients with MOGAD between 2008 and 2023 at 18 Neuromyelitis Optica Study Group centres. Treatment response was categorised as complete, partial or no remission. Preattack and follow-up Expanded Disability Status Scale (EDSS) and visual Functional System Scores (FSS) were used to calculate absolute outcomes (ΔEDSS/Δvisual FSS). Predictors of complete remission were analysed using a generalised linear mixed model., Results: Apheresis was used for 117/571 (20.5%) attacks in 85/209 (40.7%) patients. Attacks with simultaneous optic neuritis and myelitis were treated more often with apheresis (42.4%, n=14) than isolated myelitis (25.2%, n=35), cerebral manifestation (21.0%, n=17) or isolated optic neuritis (17.6%, n=51). Apheresis was initiated as first-line therapy in 12% (4.5 (IQR 0-11) days after attack onset), second-line therapy in 62% (15 (IQR 6.75-31) days) and third-line therapy in 26% (30 (IQR 19-42) days). Complete remission was achieved in 21%, partial remission in 70% and no remission in 9% of patients. First-line apheresis (OR 2.5, p=0.040) and concomitant disease-modifying therapy (OR 1.5, p=0.011) were associated with complete remission. Both parameters were also associated with a favourable ΔEDSS. No differences in outcomes were observed between the apheresis types., Conclusion: Apheresis is frequently used in MOGAD attacks. An early start as first-line therapy and concomitant disease-modifying therapy predict full attack recovery., Competing Interests: Competing interests: CS has received speaker honoraria from Alexion and travel support from Novartis and UCB, all not related to the content of this manuscript, as well as research support from FORUM (clinician scientist position), medical faculty Ruhr-Universität Bochum. TL has received travel support from UCB. VH has received research support from NEMOS independent of this project. IK has received personal compensation for consulting, serving on a scientific advisory board, speaking or other activities with Alexion, Almirall, Bayer, Biogen, GlaxoSmithKline, Hexal, Horizon, Merck, Neuraxpharm, Roche/Chugai and Sanofi, none related to this study. MR received speaker honoraria from Novartis, Bayer Vital, Roche, Alexion, Horizon and Ipsen and travel reimbursement from Bayer Schering, Biogen Idec, Merz, Genzyme, Teva, Roche, Alexion, Horizon and Merck, none related to this study. OA has received personal fees from Alexion, Bayer HealthCare, Biogen, Celgene, Merck Serono, MedImmune, Novartis, Roche, Teva and Zambon, outside the submitted work. TK has received speaker honoraria and/or personal fees for advisory boards from Novartis Pharma, Roche Pharma, Alexion/AstraZeneca, Horizon Therapeutics/Amgen, Merck, Chugai Pharma and Biogen. The institution she works for has received compensation for serving as a member of a steering committee from Roche. TK is a site principal investigator in several randomised clinical trials and her institution has received compensation for clinical trials from Novartis Pharma, Roche Pharma and Sanofi Genzyme; all outside the present work. DE received speaker honoraria and/or travel reimbursement from Alexion, Amgen/Horizon and Merck, all not related to the presented work. JH reports a grant for OCT research from the Friedrich‐Baur‐Stiftung, Horizon and Merck, personal fees and non-financial support from Alexion, Amgen, Bayer, Biogen, BMS, Merck, Novartis and Roche and non-financial support from the Sumaira Foundation and Guthy‐Jackson Charitable Foundation, all outside the submitted work. MWH received institutional research support from Myelitis, German Federal Joint Committee/Innovation Fund and NEMOS, speaker honoraria from selpers og, Horizon and Alexion and travel grants and compensation for serving on an advisory board from Alexion. None of these interfered with the current manuscript. CT received honoraria for consultation and expert testimony from Alexion Pharma Germany. None of these interfered with the current report. MK-K received speaker honoraria from BMS, Merck and Novartis. BW received research grants from Deutsche Forschungsgemeinschaft, German Ministry of Education and Research, Dietmar Hopp Foundation, Klaus Tschira Foundation, Novartis and Roche, and personal fees from Alexion, INSTAND, Novartis and Roche, all unrelated to this work. ABAGRG has received travel grants from Roche and Biogen, outside the submitted work. A-KP received speaker honoraria and research support from Biogen, none related to this study. RP received honoraria for lectures from Alexion, Bayer Healthcare, Biogen, Celgene, Horizon/Amgen, Novartis, Merck, Roche, Sanofi-Aventis and Teva. He received research grants from HERZ Burgdorf, Novartis and Merck. MK received honoraria from Roche Pharma and Chugai Pharma. FTB has received, over his academic career, research support and travel grants for attending scientific meetings, through his institution, from the German Science Fund (DFG), German Federal Ministry of Education and Science (BMBF), Bayer-Schering, Diamed, Fresenius, Merck, Novartis, Pfizer, Roche, Sanofi and Teva; speaker fees and compensation for advisory boards from Actelion, Alexion, Bayer, Biogen, CSL Behring, Fresenius, Horizon, Merck, Novartis, Roche, Sanofi-Genzyme, Takeda and Teva. None of these are related to this work. CG received honoraria from Merck. MCK has served on advisory boards and received speaker fees/travel grants from Merck, Sanofi-Genzyme, Novartis, Biogen, Janssen, Alexion, Celgene/Bristol-Myers Squibb and Roche. He has received research grants from Merck, Roche, Novartis, Sanofi-Genzyme, Janssen and Celgene/Bristol-Myers Squibb. PSR has received honoraria for lectures/consultancy from Alexion (AstraZeneca), Allmiral, Amicus, Biogen, Genzyme, Horizon (Amgen), Merck, Novartis, Roche and Teva, served on advisory boards for Alexion (AstraZeneca), Amicus, Genzyme, Horizon (Amgen), Merck, Roche and Sandoz and received research grants from Amicus, Roche, Merck and the Austrian Science Fund (FWF). IV has received travel support from Alexion. MS has received consulting and/or speaker honoraria from Alexion, Bayer, Biogen, Bristol-Myers Squibb/Celgene, Merck, Horizon, Roche and Sanofi-Genzyme. AW received speaker honoraria, consultant fees and travel reimbursement from Alexion, Bayer, Biogen, GlaxoSmithKline, Hexal, Janssen, Merck, Novartis, Pfizer, Roche, Sanofi-Genzyme and UCB, none related to this study. MSW Our research is supported by research grants (Startförderung) of the Universitätsmedizin Göttingen, the National Multiple Sclerosis Society (NMSS; PP 1660), Novartis, Teva, Biogen Idec, Roche, Merck, the ProFutura Programme of the Universitätsmedizin Göttingen and the Deutsche Forschungsgemeinschaft (WE 3547/4-1; WE 3547/5-1; WE3547/7-1; project A8, SFB TRR 274). LH has received research support and speaker honoraria from Novartis. She is supported by the Deutsche Forschungsgemeinschaft (DFG Clinician Scientist Kolleg 'Zelldynamik in Pathogenese und Therapie'). AWa received speaker honoraria and meeting expenses from Novartis, Bayer, Biogen, Sanofi-Genzyme, Teva, Roche and Merck. PSchi received travel reimbursement from UCB. FP has received research support, speaker honoraria and travel reimbursement from Bayer, Biogen Idec, Merck Serono, Novartis, Sanofi-Genzyme, UCB and Teva; is supported by the German Research Council (DFG Exc 257) and the German Competence Network for Multiple Sclerosis; received travel reimbursement from the Guthy-Jackson Charitable Foundation; and serves on the steering committee of the OCTIMS study sponsored by Novartis. JB-S has received institutional research support from NEMOS, Alexion and Bayer, personal fees from Alexion, speaker honoraria and travel grants from Bayer Healthcare, Horizon/Amgen, Novartis and Sanofi-Aventis/Genzyme, as well as grants for participating in a scientific advisory board from Roche and Merck, all unrelated to the present work. RG has received speaker and board honoraria from Baxter, Bayer Schering, Biogen Idec, CLB Behring, Genzyme, Merck Serono, Novartis, Stendhal, Talecris and Teva. His department received grant support from Bayer Schering, Biogen Idec, Genzyme, Merck Serono, Novartis and Teva. All not related to the content of this manuscript. IA received personal fees from Roche, Alexion, Horizon, Sanofi-Aventis/Genzyme and Merck and received research support from Diamed, none related to this study., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Paramagnetic rim lesions (PRLs) are an imaging biomarker in multiple sclerosis (MS), associated with a more severe disease., Objectives: To determine quantitative magnetic resonance imaging (MRI) metrics of PRLs, lesions with diffuse susceptibility-weighted imaging (SWI)-hypointense signal (DSHLs) and SWI-isointense lesions (SILs), their surrounding periplaque area (PPA) and the normal-appearing white matter (NAWM)., Methods: In a cross-sectional study, quantitative MRI metrics were measured in people with multiple sclerosis (pwMS) using the multi-dynamic multi-echo (MDME) sequence post-processing software "SyMRI.", Results: In 30 pwMS, 59 PRLs, 74 DSHLs, and 107 SILs were identified. Beside longer T1 relaxation times of PRLs compared to DSHLs and SILs (2030.5 (1519-2540) vs 1615.8 (1403.3-1953.5) vs 1199.5 (1089.6-1334.6), both p  < 0.001), longer T1 relaxation times were observed in the PRL PPA compared to the SIL PPA and the NAWM but not the DSHL PPA. Patients with secondary progressive multiple sclerosis (SPMS) had longer T1 relaxation times in PRLs compared to patients with late relapsing multiple sclerosis (lRMS) (2394.5 (2030.5-3040) vs 1869.3 (1491.4-2451.3), p  = 0.015) and also in the PRL PPA compared to patients with early relapsing multiple sclerosis (eRMS) (982 (927-1093.5) vs 904.3 (793.3-958.5), p  = 0.013)., Conclusion: PRLs are more destructive than SILs, leading to diffuse periplaque white matter (WM) damage. The quantitative MRI-based evaluation of the PRL PPA could be a marker for silent progression in pwMS., 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: N.K. has participated in meetings sponsored by, received speaker honoraria or travel funding from Alexion, BMS/Celgene, Janssen-Cilag, Merck, Novartis, Roche, and Sanofi-Genzyme and held a grant for a Multiple Sclerosis Clinical Training Fellowship Programme from the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS). V.S. has nothing to disclose. J.L. has nothing to disclose. L.H. has nothing to disclose. G.B. has participated in meetings sponsored by, received speaker honoraria or travel funding from Biogen, Celgene/BMS, Lilly, Merck, Novartis, Roche, Sanofi-Genzyme, and Teva, and received honoraria for consulting Biogen, Celgene/BMS, Novartis, Roche, Sanofi-Genzyme, and Teva. He has received unrestricted research grants from Celgene/BMS and Novartis. G.K. has participated in meetings sponsored by, received speaker honoraria or travel funding from Biogen, and received honoraria for consulting from Biogen. F.L. has participated in meetings sponsored by or received honoraria for acting as an advisor/speaker for Bayer, Biogen, Celgene/BMS, Janssen, MedDay, Merck, Novartis, Roche, Sanofi-Genzyme, and Teva. B.K. has received honoraria for speaking and for consulting from Biogen, BMS-Celgene, Johnson & Johnson, Merck, Novartis, Roche, Teva, and Sanofi-Genzyme outside of the submitted work. No conflict of interest with respect to this study. P.S.R. has received honoraria for consultancy/speaking from AbbVie, Almirall, Alexion, Biogen, Merck, Novartis, Roche, Sandoz, Sanofi-Genzyme, and Teva and has received research grants from Amicus, Biogen, Merck, and Roche. T.B. has participated in meetings sponsored by and received honoraria (lectures, advisory boards, consultations) from pharmaceutical companies marketing treatments for MS: Allergan, Bayer, Biogen, Bionorica, BMS/Celgene, GSK, GW/Jazz Pharma, Horizon, Janssen-Cilag, MedDay, Merck, Novartis, Octapharma, Roche, Sandoz, Sanofi-Genzyme, Teva, and UCB. His institution has received financial support in the past 12 months by unrestricted research grants (Biogen, Bayer, BMS/Celgene, Merck, Novartis, Roche, Sanofi-Genzyme, Teva and for participation in clinical trials in multiple sclerosis sponsored by Alexion, Bayer, Biogen, Merck, Novartis, Octapharma, Roche, Sanofi-Genzyme, Teva). H.L. has received honoraria for lectures from Novartis, Biogen, ROCHE, Merck, and Sanofi-Aventis. A.D.-B.’s position as junior group leader for Translational Morphology in Neuroscience is supported by a research grant from Biogen. She has participated in meetings sponsored by, received speaker honoraria or travel funding from Biogen, Celgene (BMS), Merck, Novartis, Roche, and Sanofi, and has received an unrestricted grant from Merck GmbH, an affiliate of Merck KGaA. S.H. has participated in meetings sponsored by or received speaker honoraria or travel funding from Biogen and Sanofi-Aventis.

Background: Paramagnetic rim lesions (PRLs) are chronic active lesions associated with a more severe disease course in multiple sclerosis (MS). Retinal layer thinning measured by optical coherence tomography (OCT) is a biomarker of neuroaxonal damage associated with disability progression in MS., Objective: We aimed to determine a potential association between OCT parameters (peripapillary retinal nerve fiber layer (pRNFL) ganglion cell-inner plexiform layer (GCIPL), inner nuclear layer (INL) thickness), and PRLs in patients with MS (pwMS)., Methods: In this cross-sectional retrospective study, we included pwMS with both 3T brain MRI and an OCT scan. Regression models were calculated with OCT parameters (pRNFL, GCIPL, INL) as dependent variables, and the number of PRLs as an independent variable adjusted for covariates., Results: We analyzed data from 107 pwMS (mean age 34.7 years (SD 10.9), 64.5% female, median disease duration 6 years (IQR 1-13), median EDSS 1.5 (range 0-6.5)). Higher number of PRLs was associated with lower pRNFL (β = -0.18; 95% CI -0.98, -0.03; p  = 0.038) and GCIPL thickness (β = -0.21; 95% CI -0.58, -0.02; p  = 0.039)., Conclusion: The association between higher number of PRLs and lower pRNFL and GCIPL thicknesses provides additional evidence that pwMS with PRLs are affected by a more pronounced neurodegenerative process.