6,485 results on '"Multiple Sclerosis therapy"'
Search Results
2. Wall-Eyed Bilateral Internuclear Ophthalmoplegia as Part of the Clinical Presentation of Pediatric Multiple Sclerosis, Successfully Treated With Therapeutic Plasma Exchange.
- Author
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Shakin S, Altman M, Hart J, Hopkins S, Lazerow P, and Caceres JA
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- Humans, Female, Child, Male, Magnetic Resonance Imaging, Plasma Exchange methods, Multiple Sclerosis complications, Multiple Sclerosis therapy, Multiple Sclerosis drug therapy, Ocular Motility Disorders etiology, Ocular Motility Disorders physiopathology, Ocular Motility Disorders therapy
- Abstract
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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- 2024
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3. Remotely-delivered exercise training program for improving physical and cognitive functions among older adults with multiple sclerosis: Protocol for an NIH stage-I randomized controlled trial.
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Zheng P, Phillips SA, Duffecy J, DeJonge SR, DuBose NG, and Motl RW
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- Aged, Female, Humans, Male, Middle Aged, Cognitive Dysfunction rehabilitation, Cognitive Dysfunction therapy, Exercise, Feasibility Studies, Mobility Limitation, Resistance Training methods, Randomized Controlled Trials as Topic, Cognition, Exercise Therapy methods, Multiple Sclerosis rehabilitation, Multiple Sclerosis therapy, Multiple Sclerosis psychology, Quality of Life
- Abstract
Background: Older adults with multiple sclerosis (MS) present with low physical activity participation, cognitive and ambulatory dysfunctions, and compromised quality of life (QOL)., Objective: We propose a NIH Stage-I, randomized controlled trial (RCT) that examines the feasibility and efficacy of a 16-week theory-based, remotely-delivered, exercise training program for improving cognitive and physical functions in older adults with MS who have moderate mobility disability without severe cognitive impairment., Methods: This Stage-I study utilizes a parallel-group RCT design. Participants (N = 50; age ≥ 50 years) will be randomly assigned into exercise training (combined aerobic and resistance exercise) or active control (flexibility and stretching) conditions. The conditions will be undertaken within a participant's home/community over a 16-week period, and monitored remotely and supported by Zoom-based chats guided by social cognitive theory (SCT) via a behavioral coach. Participants will receive training manuals and equipment, one-on-one behavioral coaching, action-planning calendars, self-monitoring logs, and SCT-based newsletters. The primary outcomes include feasibility (e.g., recruitment and retention rates), exercise behavior and physical activity; other outcomes include physical function (lower-extremity function, mobility, walking), cognition (processing speed, learning and memory, executive function), MS symptoms, QOL, and vascular function. We will collect outcome data at baseline (Week 0), post-intervention (Week 16), and follow-up (Week-32). Data analysis will follow intent-to-treat principles using linear mixed-effects models., Discussion: This Stage-I trial adopts an innovative approach for exercise training via telerehabilitation and is convenient and accessible for older adults with MS. If successful, the study will provide foundations for future research using remotely-delivered exercise intervention for managing the consequences of aging with MS., Trial Registration Number: NCT05930821., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
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- 2024
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4. Comparing the effectiveness, safety and tolerability of interventions for depressive symptoms in people with multiple sclerosis: A systematic review.
- Author
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Campese S, Lyons J, Learmonth YC, Metse A, Kermode AG, Marck CH, and Karahalios A
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- Humans, Randomized Controlled Trials as Topic, Psychotherapy methods, Multiple Sclerosis complications, Multiple Sclerosis therapy, Depression therapy, Depression etiology
- Abstract
Background: Depression is more common in people with multiple sclerosis (MS) compared to the general population. While many interventions are available for treating depressive symptoms in people with MS, it is unclear how different intervention modalities compare. This systematic review aimed to compare the reported effectiveness, safety, and tolerability of interventions for treating depressive symptoms in people with MS., Methods: We systematically searched 7 databases for randomised controlled trials (RCTs) of pharmaceutical, psychological, physical, and electromagnetic stimulation interventions which aimed to reduce depressive symptoms amongst adults with MS. Screening, data extraction and risk of bias assessment were completed by at least two independent researchers. We planned to synthesise the data using network meta-analysis, however the high risk of bias of the included trials resulted in synthesis without meta-analysis., Results: Of 1,949 citations, 31 trials (21 psychological, seven physical activity, two pharmaceutical, and one combination) were included, comprising 2,289 participants. Of the 31 eligible trials 24 were at high and six at moderate risk of bias, which precluded meta-analysis. Twenty-six trials reported on efficacy and only 16/31 reported safety and/or tolerability, using inconsistent methods., Conclusions: The current strength of the evidence for treating depressive symptoms in MS is low, therefore, we are not able to summarise or make comparisons between the treatment modalities. There is an urgent need for high-quality and diverse trials investigating treatment options for depression in people with MS. This can only be achieved if the conduct and reporting of RCTs are improved., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier B.V.)
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- 2024
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5. Study protocol of a randomized controlled trial comparing backward walking to forward walking training on balance in multiple sclerosis: The TRAIN-MS trial.
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VanNostrand M, Monaghan PG, Daugherty AM, and Fritz NE
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- Adult, Female, Humans, Male, Middle Aged, Feasibility Studies, Quality of Life, Randomized Controlled Trials as Topic, Accidental Falls prevention & control, Exercise Therapy methods, Multiple Sclerosis rehabilitation, Multiple Sclerosis therapy, Multiple Sclerosis psychology, Postural Balance, Walking
- Abstract
Balance impairment and accidental falls are a pervasive challenge faced by persons with multiple sclerosis (PwMS), significantly impacting their quality of life. While exercise has proven to be an effective intervention for improving mobility and functioning in PwMS, current exercise approaches predominantly emphasize forward walking (FW) and balance training, with variable improvements in balance and fall rates. Backward walking (BW) has emerged as a promising intervention modality for enhancing mobility and strength outcomes; however, significant gaps remain. Specifically, there is limited knowledge about the efficacy of BW interventions on outcomes such as static, anticipatory, and reactive balance, balance confidence, falls, and cognition. This randomized controlled trial aims to determine the feasibility, acceptability, and impact of 8-weeks of backward walking training (TRAIN-BW) as compared to forward walking training (TRAIN-FW). Ninety individuals with MS with self-reported walking dysfunction or ≥ 2 falls in the past 6 months will be randomized in blocks, stratified by sex and disease severity to either the TRAIN-BW or TRAIN-FW intervention groups. Adherence and retention rates will be used to determine feasibility and the Client Satisfaction Questionnaire will be used to assess acceptability. The primary outcomes will be static, anticipatory, and reactive balance. Secondary outcomes include walking velocity, balance confidence, concern about falling, cognition, physical activity, and fall rates measured prospectively for 6 months after post-testing. Additionally, the extent to which cognitive functioning influences response to intervention will be examined. Backward walking training may be an innovative intervention to address balance impairments and falls in persons with MS., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)
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- 2024
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6. Pipe dream: Remyelination therapy for multiple sclerosis.
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Deneen B
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- Humans, Animals, Myelin Sheath metabolism, Multiple Sclerosis therapy, Remyelination physiology
- Abstract
Competing Interests: Competing interests statement:The author declares no competing interest.
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- 2024
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7. White matter disease derived from vascular and demyelinating origins.
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Zhang LJ, Tian DC, Yang L, Shi K, Liu Y, Wang Y, and Shi FD
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- Humans, Prognosis, Diagnosis, Differential, Disease Progression, Magnetic Resonance Imaging, Cerebral Small Vessel Diseases diagnostic imaging, Cerebral Small Vessel Diseases therapy, Cerebral Small Vessel Diseases physiopathology, Leukoencephalopathies diagnostic imaging, Leukoencephalopathies physiopathology, Leukoencephalopathies therapy, White Matter diagnostic imaging, White Matter pathology, Multiple Sclerosis diagnostic imaging, Multiple Sclerosis physiopathology, Multiple Sclerosis therapy, Predictive Value of Tests
- Abstract
Damage or microstructural alterations of the white matter can cause dysfunction of the intrinsic neural networks in a condition termed as white matter disease (WMD). Frequently detected on brain computed tomography and magnetic resonance imaging scans, WMD is commonly presented in inflammatory demyelinating diseases like multiple sclerosis (MS) and vascular diseases such as cerebral small vessel disease (CSVD). Prevention of MS and CSVD progression requires early treatments with drastically different medications and approaches, as such, early and accurate diagnosis of WMD, derived from vascular or demyelinating etiologies, is of paramount importance. However, the clinical and imaging similarities between MS, especially during the early stage, and CSVD, pose a significant dilemma in differentiating these two conditions. In this review, we attempt to summarize and contrast the distinguishing features of MS and CSVD for aiding accurate diagnosis to ensure timely corresponding management in the early stages of MS and CSVD., Competing Interests: Competing interests: None declared., (© 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.)
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- 2024
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8. Challenges Implementing Patient and Public Involvement in a Digital Health Agile Project Which Includes Research, Business and Software Development.
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Yrttiaho T, Giunti G, and Isomursu M
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- Humans, Community Participation, Software, Software Design, Digital Health, Patient Participation, Multiple Sclerosis therapy
- Abstract
Patient and public involvement (PPI) is a practice for involving future users in the design, development, and research of health technologies. There is increasing interest and demand for PPI, but little evidence based methodological support for integrating PPI in agile development processes. Multiple sclerosis (MS) is a chronic condition that severely impacts the lives of patients and requires active patient involvement. In this paper, we present the results of a case study, examining the adoption and integration of PPI into the development of a digital therapeutics solution for MS. The results highlight five critical phases that proved to be challenging: selecting patient participants, onboarding of patient participants and employees, framing tasks for patient participants, communication between patient participants and the rest of the development team, and reimbursements. The results are useful in creating evidence-based guidelines and methods for supporting the adoption of PPI.
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- 2024
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9. A future of AI-driven personalized care for people with multiple sclerosis.
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Praet J, Anderhalten L, Comi G, Horakova D, Ziemssen T, Vermersch P, Lukas C, van Leemput K, Steppe M, Aguilera C, Kadas EM, Bertrand A, van Rampelbergh J, de Boer E, Zingler V, Smeets D, Ribbens A, and Paul F
- Subjects
- Humans, Disease Progression, Biomarkers, Quality of Life, Prognosis, Multiple Sclerosis therapy, Multiple Sclerosis immunology, Precision Medicine methods, Artificial Intelligence
- Abstract
Multiple sclerosis (MS) is a devastating immune-mediated disorder of the central nervous system resulting in progressive disability accumulation. As there is no cure available yet for MS, the primary therapeutic objective is to reduce relapses and to slow down disability progression as early as possible during the disease to maintain and/or improve health-related quality of life. However, optimizing treatment for people with MS (pwMS) is complex and challenging due to the many factors involved and in particular, the high degree of clinical and sub-clinical heterogeneity in disease progression among pwMS. In this paper, we discuss these many different challenges complicating treatment optimization for pwMS as well as how a shift towards a more pro-active, data-driven and personalized medicine approach could potentially improve patient outcomes for pwMS. We describe how the 'Clinical Impact through AI-assisted MS Care' (CLAIMS) project serves as a recent example of how to realize such a shift towards personalized treatment optimization for pwMS through the development of a platform that offers a holistic view of all relevant patient data and biomarkers, and then using this data to enable AI-supported prognostic modelling., Competing Interests: JP is a shareholder of icometrix NV. AR is a shareholder of icometrix NV. DS is a shareholder of icometrix NV. MS has no relevant or material financial interests that relate to the research described in this paper. However, she is employed as Operational Director of The European Charcot Foundation. TZ reports scientific advisory board and/or consulting for Biogen, Roche, Novartis, Celgene, and Merck; compensation for serving on speaker’s bureaus for Roche, Novartis, Merck, Sanofi, Celgene, and Biogen; and research support from Biogen, Novartis, Merck, and Sanofi. VZ is a shareholder of F. Hoffmann-La Roche Ltd PV reports honorarium, contributions to meeting from Biogen, Sanofi-Genzyme, Novartis, Teva, Merck, Roche, Imcyse, AB Science, Janssen, Ad Scientiam and BMS-Celgene. Research support from Novartis, Sanofi-Genzyme and Merck. EK is a shareholder of Nocturne GmbH. DH received compensation for travel, speaker honoraria and consultant fees from Biogen Idec, Novartis, Merck, Bayer, Sanofi Genzyme, Roche, and Teva, as well as support for research activities from Biogen Idec. JR is a shareholder of Imcyse SA. GC has received consulting and speaking fees from Novartis, Sanofi, Janssen, Bristol Myers Squibb, Roche and Rewind. FP provided research support to Neurosciences Clinical Research Center, German Ministry for Education and Research (BMBF), Deutsche Forschungsgemeinschaft (DFG), Einstein Foundation, Guthy Jackson Charitable Foundation, EU FP7 Framework Program, Biogen, Genzyme, Merck Serono, Novartis, Bayer, Roche, Parexel and Almirall, received honoraria for lectures, presentations, speakers from Guthy Jackson Foundation, Bayer, Biogen, Merck Serono, Sanofi Genzyme, Novartis, Viela Bio, Roche, UCB, Mitsubishi Tanabe and Celgene, in addition, received compensation for serving on a scientific advisory board of Celgene, Roche, UCB and Merck, and is an Academic Editor of PLos One and Associate Editor of Neurology® Neuroimmunology & Neuroinflammation, all unrelated to this work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Praet, Anderhalten, Comi, Horakova, Ziemssen, Vermersch, Lukas, van Leemput, Steppe, Aguilera, Kadas, Bertrand, van Rampelbergh, de Boer, Zingler, Smeets, Ribbens and Paul.)
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- 2024
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10. PEER CONNECT: a pragmatic feasibility randomised controlled trial of peer coaching for adults with long-term conditions.
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Dennett R, Thompson T, Clyne W, Straukiene A, Davies-Cox H, Hosking J, Bones K, and Elston J
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- Humans, Female, Middle Aged, Male, Adult, Chronic Disease therapy, Aged, Multiple Sclerosis therapy, Multiple Sclerosis psychology, England, State Medicine, Qualitative Research, Peer Group, Feasibility Studies, Mentoring methods
- Abstract
Objective: To test the feasibility of a targeted peer coaching intervention on the health and well-being of people with long-term health conditions and low activation attending outpatient clinics at a UK National Health Service (NHS) Trust., Design: Randomised controlled feasibility trial, with embedded qualitative study., Setting: An NHS integrated health and care organisation in the South West of England, UK, with significant areas of deprivation., Participants: Patients (over 18 year of age) of the Trust's rheumatology, pain or multiple sclerosis services, with a Patient Activation Measure score at level 1 or 2., Intervention: Up to 14 sessions of peer coaching delivered in a stepped-down model delivered over 6 months., Main Outcomes: Primary feasibility outcomes were recruitment, retention, intervention adherence and peer, coach and staff experience.Secondary outcomes included psychological well-being, resource use, long-term condition management and disease-specific measures., Results: 97 potential coaches were contacted directly. 27 (27.8%) were screened and of those 21 (77.8%) were eligible and recruited into the study. For a range of reasons, only five (23.8%) progressed through training and on to deliver peer coaching. 747 potential peers were invited to take part and 19 (2.5%) were screened. Of those screened, seven (36.8%) were eligible, recruited and randomised, all white females with median age of 50 years (range: 24-82 years). One peer in the intervention group withdrew prior to receiving the intervention, the remaining four received coaching. Peers and coaches reported a range of benefits related to their health and well-being., Conclusion: Coach recruitment, training and study procedures were feasible and acceptable. Due to low peer recruitment numbers, it was decided not to progress to a definitive trial. Further research is required to explore how to engage with and recruit people reporting low levels of activation and the acceptability and effectiveness of peer coaching for this group., Trial Registration Number: ISRCTN12623577., Competing Interests: Competing interests: None declared., (© 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.)
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- 2024
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11. Study protocol: effects of exercise booster sessions on preservation of exercise-induced adaptations in persons with multiple sclerosis, a multicentre randomised controlled trial-the MS BOOSTER trial.
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Taul-Madsen L, Hvid LG, Sellebjerg F, Christensen JR, Ratzer R, Sejbæk T, Svendsen KB, Papp V, Højsgaard Chow H, Lundbye-Jensen J, Dawes H, and Dalgas U
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- Humans, Adaptation, Physiological, Randomized Controlled Trials as Topic, Exercise physiology, Male, Multicenter Studies as Topic, Adult, Female, Fatigue, Multiple Sclerosis therapy, Resistance Training methods, Quality of Life, Exercise Therapy methods
- Abstract
Introduction: Multiple sclerosis (MS) causes a broad range of symptoms, with physical function being one of the most disabling consequences according to patients themselves. Exercise effectively improves lower extremity physical function. Nonetheless, it is unknown which exercise modality is most effective and it remains challenging to keep persons with MS adhering to exercise over a longer period. Therefore, the present study aims to investigate how exercise booster sessions (EBS) influence the sustainability of exercise-induced effects on physical function, and furthermore, to investigate which exercise modality (aerobic training or resistance training) is most effective in terms of improving physical function., Materials and Methods: This study is a multi-arm, parallel-group, open-label multicentre randomised controlled trial investigating the effects of EBS. Participants (n=150) are initially randomised to 12 weeks of either resistance training+usual care, aerobic training+usual care or usual care. After 12 weeks of intervention, participants in the exercise groups will again be randomised to either EBS+usual care or usual care during a 40-week follow-up period. The primary outcome is physical function (composite score based on 6-min walk test and five-time sit to stand), and the secondary outcomes are fatigue, cognition, physical activity, symptoms of depression and quality of life., Ethics and Dissemination: The study is approved by the Central Denmark Region Committees on Health Research Ethics (1-10-72-237-21) and is registered at the Danish Data Protection Agency (2016-051-000001) and at Clinicaltrials.gov (NCT04913012). All study findings will be published in scientific peer-reviewed journals and presented at scientific conferences., Trial Registration Number: NCT04913012., Competing Interests: Competing interests: LT-M, HD, RR, KBS and JL-J declare no conflict of interest. LGH has received travel grants and/or teaching honorary from Biogen and Sanofi Genzyme. UD has received research support, travel grants and/or teaching honorary from Biogen, Merck Serono, Novartis, Bayer Schering and Sanofi Aventis as well as honoraria from serving on scientific meetings of Biogen and Sanofi Genzyme. HHC reports non-financial support from Merck, non-financial support from Teva, non-financial support from Biogen, non-financial support from Roche and non-financial support from Novartis outside the submitted work and personal support from the Warwara Larsen Foundation. FS has served on scientific advisory boards for, served as consultant for, received support for congress participation or received speaker honoraria from Alexion, Biogen, Bristol Myers Squibb, Lundbeck, Merck, Novartis, Roche and Sanofi Genzyme. His laboratory has received research support from Biogen, Merck, Novartis, Roche and Sanofi Genzyme. VP has received travel grants from Merck and Sanofi and research support from Roche. JRC has received speaker honoraria from Biogen. RR has served on scientific advisory boards, received speaker honoraria and received support for congress participation from Merck, Sanofi, Roche, Medtronic and Ipsen. TS has served on scientific advisory boards for, served as consultant for, received support for congress participation or received speaker honoraria from Biogen, Merck, Novartis, Roche and Sanofi. TS received unrestricted research grants to his research institution from Biogen, Merck and Roche, and is currently engaged in sponsor-initiated research projects by Eisai, Lundbeck, Roche and Sanofi., (© 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.)
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- 2024
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12. Value of Optic Nerve MRI in Multiple Sclerosis Clinical Management: A MAGNIMS Position Paper and Future Perspectives.
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Sastre-Garriga J, Vidal-Jordana A, Toosy AT, Enzinger C, Granziera C, Frederiksen J, Ciccarelli O, Filippi M, Montalban X, Tintore M, Pareto D, and Rovira À
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- Humans, Optic Neuritis diagnostic imaging, Optic Neuritis therapy, Disease Management, Multiple Sclerosis diagnostic imaging, Multiple Sclerosis therapy, Magnetic Resonance Imaging methods, Optic Nerve diagnostic imaging, Optic Nerve pathology
- Abstract
The optic nerve is frequently involved in multiple sclerosis (MS). However, MRI of the optic nerve is considered optional in the differential diagnosis of optic neuropathy symptoms either at presentation or in established MS. In addition, unlike spinal cord imaging in comparable scenarios, no role is currently recommended for optic nerve MRI in patients presenting with optic neuritis for its confirmation, to plan therapeutic strategy, within the MS diagnostic framework, nor for the detection of subclinical activity in established MS. In this article, evidence related to these 3 aspects will be summarized and gaps in knowledge will be highlighted, including (1) the acquisition challenges and novel sequences that assess pathologic changes within the anterior visual pathways; (2) the clinical implications of quantitative magnetic resonance studies of the optic nerve, focusing on atrophy measures, magnetization transfer, and diffusion tensor imaging; and (3) the relevant clinical studies performed to date. Finally, an algorithm for the application of optic nerve MRI will be proposed to guide future studies aimed at addressing our knowledge gaps.
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- 2024
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13. Low intensity repetitive transcranial magnetic stimulation enhances remyelination by newborn and surviving oligodendrocytes in the cuprizone model of toxic demyelination.
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Nguyen PT, Makowiecki K, Lewis TS, Fortune AJ, Clutterbuck M, Reale LA, Taylor BV, Rodger J, Cullen CL, and Young KM
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- Animals, Mice, Disease Models, Animal, Mice, Transgenic, Motor Cortex pathology, Motor Cortex metabolism, Cell Survival, Mice, Inbred C57BL, Multiple Sclerosis therapy, Multiple Sclerosis pathology, Cuprizone, Transcranial Magnetic Stimulation methods, Oligodendroglia metabolism, Remyelination, Demyelinating Diseases therapy, Demyelinating Diseases chemically induced, Demyelinating Diseases pathology, Myelin Sheath metabolism
- Abstract
In people with multiple sclerosis (MS), newborn and surviving oligodendrocytes (OLs) can contribute to remyelination, however, current therapies are unable to enhance or sustain endogenous repair. Low intensity repetitive transcranial magnetic stimulation (LI-rTMS), delivered as an intermittent theta burst stimulation (iTBS), increases the survival and maturation of newborn OLs in the healthy adult mouse cortex, but it is unclear whether LI-rTMS can promote remyelination. To examine this possibility, we fluorescently labelled oligodendrocyte progenitor cells (OPCs; Pdgfrα-CreER transgenic mice) or mature OLs (Plp-CreER transgenic mice) in the adult mouse brain and traced the fate of each cell population over time. Daily sessions of iTBS (600 pulses; 120 mT), delivered during cuprizone (CPZ) feeding, did not alter new or pre-existing OL survival but increased the number of myelin internodes elaborated by new OLs in the primary motor cortex (M1). This resulted in each new M1 OL producing ~ 471 µm more myelin. When LI-rTMS was delivered after CPZ withdrawal (during remyelination), it significantly increased the length of the internodes elaborated by new M1 and callosal OLs, increased the number of surviving OLs that supported internodes in the corpus callosum (CC), and increased the proportion of axons that were myelinated. The ability of LI-rTMS to modify cortical neuronal activity and the behaviour of new and surviving OLs, suggests that it may be a suitable adjunct intervention to enhance remyelination in people with MS., (© 2024. The Author(s).)
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- 2024
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14. Effects of a Digital Care Pathway for Multiple Sclerosis: Observational Study.
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Vesinurm M, Maunula A, Olli P, Lillrank P, Ijäs P, Torkki P, Mäkitie L, and Laakso SM
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- Humans, Male, Female, Middle Aged, Adult, Patient Satisfaction, Critical Pathways, Case-Control Studies, Finland, Telemedicine, Surveys and Questionnaires, Multiple Sclerosis psychology, Multiple Sclerosis therapy
- Abstract
Background: Helsinki University Hospital has developed a digital care pathway (DCP) for people with multiple sclerosis (MS) to improve the care quality. DCP was designed for especially newly diagnosed patients to support adaptation to a chronic disease., Objective: This study investigated the MS DCP user behavior and its impact on patient education-mediated changes in health care use, patient-perceived impact of MS on psychological and physical functional health, and patient satisfaction., Methods: We collected data from the service launch in March 2020 until the end of 2022 (observation period). The number of users, user logins, and their timing and messages sent were collected. The association of the DCP on health care use was studied in a case-control setting in which patients were allowed to freely select whether they wanted to use the service (DCP group n=63) or not (control group n=112). The number of physical and remote appointments either to a doctor, nurse, or other services were considered in addition to emergency department visits and inpatient days. The follow-up time was 1 year (study period). Furthermore, a subgroup of 36 patients was recruited to fill out surveys on net promoter score (NPS) at 3, 6, and 12 months, and their physical and psychological functional health (Multiple Sclerosis Impact Scale) at 0, 3, 6, and 12 months., Results: During the observation period, a total of 225 patients had the option to use the service, out of whom 79.1% (178/225) logged into the service. On average, a user of the DCP sent 6.8 messages and logged on 7.4 times, with 72.29% (1182/1635) of logins taking place within 1 year of initiating the service. In case-control cohorts, no statistically significant differences between the groups were found for physical doctors' appointments, remote doctors' contacts, physical nurse appointments, remote nurse contacts, emergency department visits, or inpatient days. However, the MS DCP was associated with a 2.05 (SD 0.48) visit increase in other services, within 1 year from diagnosis. In the prospective DCP-cohort, no clinically significant change was observed in the physical functional health between the 0 and 12-month marks, but psychological functional health was improved between 3 and 6 months. Patient satisfaction improved from the NPS index of 21 (favorable) at the 3-month mark to the NPS index of 63 (excellent) at the 12-month mark., Conclusions: The MS DCP has been used by a majority of the people with MS as a complementary service to regular operations, and we find high satisfaction with the service. Psychological health was enhanced during the use of MS DCP. Our results indicate that DCPs hold great promise for managing chronic conditions such as MS. Future studies should explore the potential of DCPs in different health care settings and patient subgroups., (©Märt Vesinurm, Anna Maunula, Päivi Olli, Paul Lillrank, Petra Ijäs, Paulus Torkki, Laura Mäkitie, Sini M Laakso. Originally published in JMIR Human Factors (https://humanfactors.jmir.org), 07.08.2024.)
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- 2024
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15. Quality of reporting health behaviors for multiple sclerosis (QuoRH-MS): A scoping review to inform intervention planning and improve consistency of reporting.
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Probst Y and Kinnane E
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- Humans, Exercise, Quality of Life, Multiple Sclerosis therapy, Multiple Sclerosis psychology, Health Behavior
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Background: Multiple sclerosis (MS) is a neurological condition that necessitates a multidisciplinary approach to aid those living with MS in managing their disease. Health behavior, or lifestyle modification, is an emerging approach to MS self-management. MS researchers utilize measurement tools to ensure that interventions are best suited to the outcomes, thereby potentially influencing practice. The aim of this study was to investigate which tools are being used for health behavior management studies in people living with MS and develop an aid for tool selection., Methods: A scoping review guided by the PRISMA-Sc checklist and the JBI manual for evidence synthesis was employed with a systematic search strategy executed across four scientific databases: Medline, PubMed, CINAHL, and Cochrane Libraries. The types of assessment tools used were extracted from the included studies. Each tool was categorized into the health behavior intervention discipline (nutrition, exercise, and psychology) and then subcategorized by the tool's purpose. The frequency of use was determined for each tool. Reporting of validation of the assessment tools were collated to inform a tool selection checklist., Results: The review identified a total of 248 tools (12 nutrition, 55 exercise, and 119 psychology unique reports) from 166 studies. Seventy-seven multidimensional tools were identified including measures of quality of life, fatigue, and functional scales. Only 88 studies (53%) referred to the validity of the tools. The most commonly reported tools were the dietary habits questionnaire (n = 4, nutrition), 6-minute walk test (n = 17, exercise), Symbol Digits and Modalities Test, and Hospital Anxiety and Depression Scale (n = 15 each, psychology) with the Expanded Disability Status Scale reported 43 times., Conclusion: Evidence from interventions may inform practice for health professionals. This review provides insights into the range of tools reported across health behavior intervention studies for MS and offers a guide toward more consistent reporting of study methods., (© 2024 The Author(s). Brain and Behavior published by Wiley Periodicals LLC.)
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- 2024
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16. [Tumefactive Demyelinating Lesions].
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Mizumoto Y and Abe T
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- Humans, Magnetic Resonance Imaging, Multiple Sclerosis diagnosis, Multiple Sclerosis pathology, Multiple Sclerosis therapy, Demyelinating Diseases diagnosis, Demyelinating Diseases pathology, Demyelinating Diseases therapy
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Tumefactive demyelinating lesions (TDL), defined as inflammatory demyelinating lesions, may develop either during treatment for multiple sclerosis and related disorders or as the first demyelinating episode without any past medical history suggesting demyelination. If the latter, it would be so delicate to diagnose as demyelination. Especially in such situations, biopsy is often necessary in addition to neuroimaging for distinction TDL with tumorous or infectious diseases. In this article, we will review about concept, epidemiology, diagnosis, and treatment of TDL.
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- 2024
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17. Using the Knowledge to Action framework to improve housing and support for people with Multiple Sclerosis.
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Cubis L, McDonald S, Dean P, Ramme R, D'Cruz K, Topping M, Fisher F, Winkler D, and Douglas J
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- Humans, Male, Female, Middle Aged, Adult, Australia, Disabled Persons psychology, Disabled Persons rehabilitation, Independent Living, Aged, Social Support, Multiple Sclerosis therapy, Multiple Sclerosis psychology, Housing
- Abstract
Background People with Multiple Sclerosis (MS) have unique housing and support needs that are essential for maintaining independence at home; however, there is limited research to guide the design of community living options for this population. The aim of this study was to examine housing and support needs and preferences of people with MS with the intention to inform the planning of a co-designed intervention based on the study's findings. Methods Using the Knowledge to Action (KTA) framework, quantitative (n =79) and qualitative (n =6) data from people with MS were extracted and integrated from projects completed by the research team that explored the housing and support needs and preferences of people with disability. Results were synthesised and presented to a reference group for validation, contextualisation, and adaptation to the Australian context. Results High physical support needs were common across participants. People most commonly required home modifications to improve accessibility, such as ramps, equipment such as heating and cooling, and assistive technology. Many people required more than 8 hours per day of paid support. Moving into individualised housing facilitated independence and community reintegration. People reported gaps between what they wanted from support workers and what they received, citing individual and systemic barriers. Conclusion People with MS have support needs that require proactive and responsive funding arrangements, housing design and support provision. In line with KTA principles, findings will inform the planning of a co-designed intervention that involves people with lived experience of MS and other stakeholders to influence policy and improve home and living outcomes for this population.
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- 2024
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18. [Uveitis and multiple sclerosis : Clinical aspects, diagnostics, management and treatment].
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Stübiger N, Ruprecht K, and Pleyer U
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- Humans, Diagnosis, Differential, Immunotherapy methods, Female, Multiple Sclerosis diagnosis, Multiple Sclerosis therapy, Uveitis diagnosis, Uveitis therapy, Uveitis drug therapy
- Abstract
Approximately 0.5-1% of patients with multiple sclerosis (MS) have co-existing uveitis. Both intraocular inflammation and MS mainly affect women in younger adulthood. The MS in patients is most frequently associated with an often bilateral intermediate uveitis with typical concomitant retinal vasculitis. Both diseases share similar characteristics with chronic inflammatory diseases with a relapsing course and an immune-mediated pathogenesis; however, it is still unclear whether the co-occurrence of uveitis and MS in the same patient represents a coincidence of two separate disease entities or whether uveitis is a rare clinical manifestation of MS. In the differential diagnostics of intermediate uveitis, clinical symptoms and signs of MS should be considered. As both diseases are considered to be immune-mediated, immunotherapy is the main treatment option. In recent years the range of medications has expanded and includes several disease modifying drugs (biologics). When selecting the active substance it must be taken into account that tumor necrosis factor (TNF) alpha blockers are contraindicated in patients with MS., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)
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- 2024
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19. Development of Fewer Falls in MS-An Online, Theory-Based, Fall Prevention Self-Management Programme for People With Multiple Sclerosis.
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Johnson ST, Ytterberg C, Peterson E, Johansson S, Kierkegaard M, Gottberg K, and Flink M
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- Humans, Female, Internet, Self Care, Program Development, Male, Accidental Falls prevention & control, Multiple Sclerosis therapy, Self-Management
- Abstract
Objective: The aim of this study was to describe the process used to develop a theory-based, online fall prevention self-management programme for ambulatory and non-ambulatory people with multiple sclerosis (pwMS)., Methods: The development process was guided by the Medical Research Council framework of complex interventions and began with a scoping review of the literature on self-management of falls in pwMS. Subsequent phases of development were performed through iterative and concurrent processes and were informed by the perspectives of pwMS and healthcare professionals with MS expertise., Results: Through a systematic and iterative process in close collaboration with pwMS and healthcare professionals, a theory-based online fall prevention self-management programme, Fewer Falls in MS, for ambulatory and non-ambulatory pwMS was developed. The programme is grounded in theory and pedagogical models and features utilization of action plans to address diverse influences on fall risks., Conclusions: A carefully operationalized definition of self-management and an iterative co-development process were essential to the creation of the Fewer falls in MS programme. Continuation of the co-development process and collaboration with end users was needed to refine the programme., Patient or Public Contribution: PwMS and healthcare professionals were involved throughout the development process of the programme. The patient organization Neuro Sweden was contacted in the initial phase to discuss the relevance of a self-management programme to prevent falls in MS. They supported the research group (all authors) in identification of and contact with pwMS with interest to participate. Three members of the research group (S.T.J., M.F. and C.Y.), that is, the operative group, met neuro Sweden and one pwMS to further discuss the relevance of a self-management programme to prevent falls. To develop the process and content of the fall prevention programme, a co-design process was performed together with pwMS and healthcare professionals. The results of the co-design process are presented in this manuscript. In addition to participating in the co-design process, pwMS and healthcare professionals provided feedback to the research group on programme process and content on several occasions during the subsequent programme development process. In a pretest (Beta version) of the programme, four pwMS acted as test subjects and provided additional feedback on the programme to the research group., Trial Registration: NCT04317716., (© 2024 The Author(s). Health Expectations published by John Wiley & Sons Ltd.)
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- 2024
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20. 'There's Nothing Wrong With You; You Just Need to Lose Weight'-A Qualitative Exploration of Pelvic Floor Dysfunction Among Women With Multiple Sclerosis and Their Interaction in Seeking Pelvic Healthcare.
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Addington C, Bradshaw A, Hagen S, and McClurg D
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- Humans, Female, Middle Aged, United Kingdom, Adult, Pelvic Floor Disorders psychology, Pelvic Floor Disorders therapy, Interviews as Topic, Patient Acceptance of Health Care psychology, Social Stigma, Multiple Sclerosis psychology, Multiple Sclerosis therapy, Qualitative Research, Focus Groups
- Abstract
Introduction: Within 10 years of multiple sclerosis (MS) progression, nearly all women will have experienced symptoms associated with bladder, bowel and/or sexual health. Yet despite the impact these symptoms have on physical, psychological and social well-being, it remains an underserved area within the UK healthcare system., Study Aim: This research employs a participatory research approach framed within the principles of intersectional feminism to collaboratively investigate the lived experiences of pelvic floor dysfunction (PFD) and healthcare interactions among UK-based women with MS., Setting and Participants: Women residing in the United Kingdom with MS were invited to participate in online interviews facilitated by the primary author., Analysis: A thematic framework analysis offering a structured yet adaptable approach to data collection and interpretation., Results: One focus group involving four women with MS and seven individual, one-to-one interviews with women with MS provided insights into the challenges associated with navigating both MS and PFD. Four main themes included: Navigating MS and PFD; Cycles of Control; Mind, Mobility and Bladder Embodiment; Silenced Voices: The Impact of Taboos/Stigma/Dismissal on Preventing Access and Resistance through Collective Community. Six subthemes were also identified. Taken together, these themes cumulatively reflect PFD as an unmet healthcare need., Conclusion: Our findings underscore negative healthcare experiences, inadequate information provision and unmet needs related to PFD, emphasising the compounding effects of gender and disability biases., Impact: We hope that these insights can lay the groundwork for developing tailored therapeutic interventions and improved PFD healthcare for women with MS. Potential solutions include using existing MS support communities., Public Contributions: Women with MS were actively involved in co-producing interview scripts for one-to-one interviews. The primary author shared study findings at an MS group event, engaging in discussions with over 30 individuals, including people with MS and their loved ones. MS advocates played a pivotal role in contextualising the study within the broader lived experience of MS., (© 2024 The Author(s). Health Expectations published by John Wiley & Sons Ltd.)
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- 2024
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21. Real-world evidence from Germany and the United States: Treatment initiation on low-efficacy versus high-efficacy therapies in patients with multiple sclerosis.
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Papukchieva S, Kim HD, Stratil AS, Magurne E, Jonckheere A, Kahn M, Schneeweiss S, Ziemssen T, and Friedrich B
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- Humans, Germany, United States, Adult, Male, Female, Middle Aged, Immunologic Factors therapeutic use, Longitudinal Studies, Young Adult, Multiple Sclerosis therapy, Multiple Sclerosis drug therapy
- Abstract
Background: The hit-hard-and-early (HHAE) strategy where treatment is initiated with high-efficacy therapies opposed to low-efficacy therapies presents a potential paradigm shift in multiple sclerosis (MS) management. This study aimed to assess the adoption of the HHAE strategy in Germany and the United States (US) from 2020 to 2022 based on real-world data., Methods: The analysis was based on longitudinal, patient-level data from Germany and the US. For Germany, data was extracted from the Permea platform covering approximately 44 % of all German community pharmacy dispensing. For the US, data from the Komodo Healthcare Map™ was utilized, covering medical benefit data from around 88 % of the US patient population. Patients ≥18 years old and who had at least 2 prescriptions for MS-related disease-modifying drugs (DMDs) between January 2020 and December 2022 were included. To approximate therapy beginners, a washout period of one year before treatment start was applied, excluding all patients who had an MS-related DMD prescription or claim in 2019. Cohort entry date was the day of the first MS-related DMD dispense or claim. DMDs were classified as high-efficacy and low-efficacy based on the Multiple Sclerosis Therapy Consensus Group (MSTCG). Group differences were assessed with two-sided χ
2 -square and t-tests., Results: 29,604 MS therapy beginners were identified in the German and 49,791 MS therapy beginners were identified in the US dataset. 29.6 % of MS therapy beginners in Germany and 61.6 % in the US followed the HHAE strategy. Between 2020 and 2022, a significant 14 % increase in the HHAE strategy was observed in both countries (p < 0.0001). High-efficacy therapy beginners switched from their initially prescribed therapy less frequently than low-efficacy therapy beginners: 6.9 % of high-efficacy vs. 19.5 % of low-efficacy therapy beginners in Germany (p < 0.0001) and 5.5 % of high-efficacy vs. 25.0 % low-efficacy therapy beginners in the US (p < 0.0001) switched from their first prescribed DMD., Conclusion: Between 2020 and 2022, the adoption of the HHAE strategy increased in both countries, with the US exhibiting nearly double the adoption rates. High-efficacy therapy beginners were less likely to switch from their initially prescribed medication than low-efficacy therapy beginners. Real world evidence can provide valuable insights into rapidly changing treatment patterns in patients with MS., Competing Interests: Declaration of competing interest SP, A-SS, MK, and BF are employees of Temedica GmbH. H-DK, EM, AJ are employees for Komodo Health, Inc. TZ reports grants and personal fees from Biogen, Roche, Merck, TEVA and Almirall; grants, personal fees and non-financial support from Genzyme and Novartis and personal fees from Bayer, BAT, Celgene and Gilead. SS is participating in investigator-initiated grants to the Brigham and Women's Hospital from Boehringer Ingelheim, Takeda, and UCB unrelated to the topic of this study. He is a consultant to Aetion Inc., a software manufacturer of which he owns equity. He is an advisor to Temedica GmbH. His interests were declared, reviewed, and approved by the Brigham and Women's Hospital in accordance with their institutional compliance policies., (Copyright © 2024. Published by Elsevier B.V.)- Published
- 2024
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22. Artificial Intelligence and Multiple Sclerosis.
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Amin M, Martínez-Heras E, Ontaneda D, and Prados Carrasco F
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- Humans, Machine Learning, Multiple Sclerosis diagnosis, Multiple Sclerosis therapy, Artificial Intelligence
- Abstract
In this paper, we analyse the different advances in artificial intelligence (AI) approaches in multiple sclerosis (MS). AI applications in MS range across investigation of disease pathogenesis, diagnosis, treatment, and prognosis. A subset of AI, Machine learning (ML) models analyse various data sources, including magnetic resonance imaging (MRI), genetic, and clinical data, to distinguish MS from other conditions, predict disease progression, and personalize treatment strategies. Additionally, AI models have been extensively applied to lesion segmentation, identification of biomarkers, and prediction of outcomes, disease monitoring, and management. Despite the big promises of AI solutions, model interpretability and transparency remain critical for gaining clinician and patient trust in these methods. The future of AI in MS holds potential for open data initiatives that could feed ML models and increasing generalizability, the implementation of federated learning solutions for training the models addressing data sharing issues, and generative AI approaches to address challenges in model interpretability, and transparency. In conclusion, AI presents an opportunity to advance our understanding and management of MS. AI promises to aid clinicians in MS diagnosis and prognosis improving patient outcomes and quality of life, however ensuring the interpretability and transparency of AI-generated results is going to be key for facilitating the integration of AI into clinical practice., (© 2024. The Author(s).)
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- 2024
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23. Disease modifying treatment guidelines for multiple sclerosis in the United Arab Emirates.
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Jacob A, Shatila AO, Inshasi J, Massouh J, Mir R, Noori S, and Yamout B
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- Humans, Immunologic Factors therapeutic use, Practice Guidelines as Topic standards, United Arab Emirates, Multiple Sclerosis therapy, Multiple Sclerosis drug therapy
- Abstract
The newly constituted National Multiple Sclerosis (MS) Society (NMSS)of the United Arab Emirates (UAE), set up a scientific committee to create a MS disease modifying treatment (DMT) guideline for UAE. The committee considered several unique features of the MS community in UAE including large number of expatriate population, wide variations in health insurance coverage, physician and patient preferences for DMT. The overall goal of the treatment guideline is to facilitate the most appropriate DMT to the widest number of patients. To this end it has adapted recommendations from various health systems and regulatory authorities into a pragmatic amalgamation of best practices from across the world. Importantly where data is unavailable or controversial, a common sense approach is taken rather than leave physicians and patients in limbo. The committee classifies MS into subcategories and suggests appropriate treatment choices. It recommends treatment of RIS and CIS with poor prognostic factors. It largely equates the efficacy and safety of DMT with similar mechanisms of action or drug classes e.g. ocrelizumab is similar to rituximab. It allows early switching of treatment for unambiguous disease activity and those with progression independent of relapses. Autologous hematopoietic stem cell transplantation can be offered to patients who fail one high efficacy DMT. Pragmatic guidance on switching and stopping DMT, DMT choices in pregnancy, lactation and pediatric MS have been included. It is expected that these guidelines will be updated periodically as new data becomes available., Competing Interests: Declaration of competing interest Anu Jacob has received advisory board fees and speakers fee from Astra Zeneca. Ahmed Shatila has received speaker's honoraria, advisory board fees, travel grants from Novartis, Sanofi Genzyme, Roche, Merck, Jansen, Biologix, pfizer, Boehringer Ingelheim, AstraZeneca, Lundbeck and Argenx, Bayer, Biogen and received research grants from Novartis, AstraZeneca and Argenx. Jihad Inshasi has received speaker's honoraria from Bayer, Biogen, Biologix, Merck, Novartis, Roche, Sanofi; Research grants from Merck, Novartis; Advisory board fees from Bayer, Biogen,Merck, Novartis, Roche, Sanofi Joelle Massouh has received speakers’ honoraria, travel, grants and advisory board fees from AstraZeneca, Biogen, Biologix, Janssen, Merck, Novartis, Roche, and Sanofi. Ruquia Mir has received speaker's honoraria, advisory board fees and travel grants from Merck Sanofi Novartis Roche Suzan Noori has no disclosures. Bassem Yamout has received speaker's honoraria travel, grants and advisory board fees from Bayer, Biogen, Biologix, Genpharm, Merck, Novartis, Roche, Sanofi, Genzyme and research grants from Bayer, Biogen, Biologix, Merck, Novartis, Pfizer, (Copyright © 2024. Published by Elsevier B.V.)
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- 2024
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24. Sexual Health Education and Quality of Counseling in Pediatric-Onset Multiple Sclerosis.
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Burk K, Pagarkar D, Khoshnood MM, Jafarpour S, Ahsan N, Mitchell WG, and Santoro JD
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- Humans, Female, Adolescent, Male, Young Adult, Adult, Pregnancy, Cohort Studies, Sex Education, Pilot Projects, Family Planning Services, Multiple Sclerosis therapy, Multiple Sclerosis ethnology, Health Knowledge, Attitudes, Practice ethnology, Sexual Health, Counseling standards, Hispanic or Latino
- Abstract
Background: Disease-modifying therapies (DMTs) have revolutionized the management of multiple sclerosis (MS). Many DMTs have a risk of teratogenic outcomes, which is notable as MS disproportionally affects women of reproductive age and the rates of unplanned pregnancies among persons with MS (PwMS) are as high as 34%. Prior research suggests that patients' culture may influence their perspectives surrounding family planning. Given our institution's patient population, we compared the spectrum of knowledge in Hispanic and non-Hispanic patients with pediatric-onset MS (POMS) regarding DMTs and their associated risks during pregnancy and possible disparities in their treatment and counseling., Methods: A small cohort of patients with POMS (n = 22) were surveyed on their knowledge and beliefs surrounding family planning and sexual health counseling. Odds ratios and 95% confidence intervals were used to evaluate the association between survey question responses and ethnicity., Results: No significant differences in beliefs or knowledge regarding sexual health between Hispanic and non-Hispanic participants were identified, but many valuable themes emerged. Internet access and social relationships heavily influence participants' knowledge surrounding birth control and sexual health. Patients also desired continuous engagement in sexual health counseling., Conclusions: In this small pilot cohort, cultural views did not significantly influence whether adolescent and young adult patients with POMS seek sexual health resources. Future studies should aim to identify effective interventions for providers to educate PwMS about sexual health and family planning to address the elevated unplanned pregnancy rate in this population and provide the education these patients have vocalized a desire to receive., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)
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- 2024
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25. Improving prospective memory in persons with multiple sclerosis via telehealth: A randomized feasibility study.
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Gromisch ES, Turner AP, Neto LO, Haselkorn JK, and Raskin SA
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- Humans, Male, Female, Middle Aged, Adult, Patient Satisfaction, Feasibility Studies, Multiple Sclerosis rehabilitation, Multiple Sclerosis therapy, Multiple Sclerosis complications, Telemedicine, Memory, Episodic, Memory Disorders etiology, Memory Disorders rehabilitation, Memory Disorders therapy
- Abstract
Background: Persons with multiple sclerosis (PwMS) can experience deficits in prospective memory (PM) or "remembering to remember," which are associated with functional difficulties. However, no cognitive rehabilitation intervention has specifically addressed improving PM in PwMS. The Telehealth PM Intervention (TPMI) provides a novel combination of two strategies-visual imagery and implementation intentions-that have each been beneficial in other populations. This study aimed to evaluate the feasibility of TPMI and its preliminary efficacy, which could be used to inform future trials., Methods: Participants (n = 35) were PwMS who were pre-screened and endorsed experiencing problems "remembering places they have to be" and "things they have to do." After completing a baseline evaluation, which included objective (Memory for Intentions Test; MIST) and subjective (Perceived Deficits Questionnaire; PDQ-PM) measures of PM, participants were randomized to either the active treatment (TPMI; n = 17) or active control group (Control; n = 18). TPMI was offered through remote one-on-one sessions twice a week over a four-week period. Participants were asked about treatment credibility and expectancy during the first session. The MIST and PDQ-PM were repeated at post-treatment, where treatment satisfaction was also captured. Mann-Whitney U and chi-square tests were used to examine the feasibility measures, while repeated measures ANOVAs were used to examine changes in the PM outcomes., Results: A total of 88.2 % of the TPMI group completed all eight sessions, with moderate-to-high (≥7 out of 10) treatment credibility/expectancy and satisfaction reported by 93.3 % and 86.7 %, respectively. While there were no significant effects on overall PM, the TPMI group had an improvement in objective time-based PM after adjusting for baseline differences (F(1,29) = 4.61, p = 0.040; d = 0.80). Furthermore, the TPMI group had a significant reduction in the number of time-based loss of content errors compared to the Control group, which remained significant after covariate adjustment (F(1,25) = 4.29, p = 0.049; d = 0.83)., Conclusions: TPMI is a feasible intervention, with high completion rates and moderate-to-high treatment ratings, that can be delivered remotely. Early evidence shows its potential benefit for improving time-based PM, a particular concern for PwMS, which should be further evaluated in a larger clinical trial., Competing Interests: Declaration of competing interest Dr. Raskin in the developer of the MIST. The authors have no other competing interests to declare., (Copyright © 2024. Published by Elsevier B.V.)
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- 2024
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26. Neuropsychology intervention for managing invisible symptoms of MS (NIMIS-MS) group: A pilot effectiveness and acceptability study.
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O'Keeffe F, Cogley C, McManus C, Davenport L, O'Connor S, Tubridy N, Gaughan M, McGuigan C, and Bramham J
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- Humans, Male, Female, Middle Aged, Pilot Projects, Adult, Acceptance and Commitment Therapy methods, Psychotherapy, Group methods, Cognitive Dysfunction etiology, Cognitive Dysfunction rehabilitation, Cognitive Dysfunction therapy, Cognitive Behavioral Therapy methods, Patient Education as Topic, Patient Acceptance of Health Care, Depression therapy, Depression etiology, Multiple Sclerosis complications, Multiple Sclerosis rehabilitation, Multiple Sclerosis psychology, Multiple Sclerosis therapy
- Abstract
Background: People with MS (pwMS) commonly experience a range of hidden symptoms, including cognitive impairment, anxiety and depression, fatigue, pain, and sensory difficulties. These "invisible" symptoms can significantly impact wellbeing, relationships, employment and life goals. We developed a novel bespoke online group neuropsychological intervention combining psychoeducation and cognitive rehabilitation with an Acceptance and Commitment Therapy (ACT)-informed approach for pwMS in an acute tertiary hospital. This 'Neuropsychological Intervention for Managing Invisible Symptoms' in MS (NIMIS-MS) consisted of 6 sessions, each with a psychoeducation and ACT component. The content included psychoeducation around managing cognitive difficulties, fatigue, pain, sleep and other unpleasant sensations in MS with the general approach of understanding, monitoring, and recognising patterns and potential triggers. Specific cognitive rehabilitation and fatigue management strategies were introduced. The ACT-informed component focussed on three core ACT areas of the 'Triflex' of psychological flexibility (Harris, 2019): Being Present, Opening Up, and Doing What Matters., Methods: 118 pwMS attended the NIMIS-MS group intervention which was delivered 14 times in six-week blocks over an 18-month period. To evaluate the effectiveness and acceptability, participants completed measures of depression and anxiety (HADS), functional impairment (WSAS), Values- Progress (VQ) and Values- Obstruction (VQ), and Acceptance of MS (MSAS) pre and post NIMIs-MS group intervention. Qualitative feedback was obtained during focus groups after the final session and via online feedback questionnaires RESULTS: Pre-post analysis showed that symptoms of depression and anxiety were significantly lower and acceptance of MS was significantly higher following completion of the NIMIS-MS group. Qualitative feedback showed that participants reported that they felt more equipped to manage the "invisible" symptoms of MS following completion of the group, and benefited from using ACT-based strategies and techniques. Participants highly valued the peer support that evolved during the NIMIS-MS groups. The online format was considered more accessible than in-person groups, due to less concerns of travel time, cost, fatigue, and comfort and infection., Conclusion: Evaluation suggests that our novel NIMIS-MS groups is an acceptable, beneficial and feasible approach for providing neuropsychological interventions to individuals with MS., Competing Interests: Declaration of competing interest The authors do not have any competing or conflicting interests to declare., (Copyright © 2024. Published by Elsevier B.V.)
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- 2024
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27. Neuropsychological outcomes following HSCT in MS: A systematic review.
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Davenport L, McCauley M, Breheny E, Smyth L, Gaughan M, Tubridy N, McGuigan C, and O'Keeffe F
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- Humans, Quality of Life, Fatigue etiology, Outcome Assessment, Health Care, Hematopoietic Stem Cell Transplantation adverse effects, Multiple Sclerosis complications, Multiple Sclerosis therapy
- Abstract
Background: Autologous haematopoietic stem cell transplant (HSCT) is considered an effective treatment for highly active multiple sclerosis (MS). To date, most research has focused primarily on disease outcome measures, despite the significant impact of neuropsychological symptoms on MS patients' quality of life. The current systematic review aimed to examine whether HSCT for MS impacts neuropsychological outcome measures such as cognition, fatigue, mood, and quality of life., Methods: The review was registered with the International Prospective Register of Systematic Reviews (PROSPERO, ID: CRD42023474214). Systematic searches were carried out in six databases (PsycINFO, PubMed, Embase, Scopus, CINAHL and Web of Science) based on the following inclusion criteria: (i) published in peer-reviewed journals in English; (ii) longitudinal studies of adults with MS (iii) at least one neuropsychological outcome was assessed pre- and post-HSCT using standardised measures. Risk of bias was assessed using the National Heart, Lung and Blood Institute (NHLBI) quality assessment tools. A narrative synthesis was used to present results., Results: Eleven studies were included in the review. Long-term improvements in quality of life post-HSCT were identified. In terms of cognition and fatigue, the evidence was mixed, with some post-HSCT improvements identified. Decline in cognitive performance in the short-term post-HSCT was observed. No changes in mood were identified post-HSCT. Arguments for interpreting these results with caution are presented based on risk of bias. Arguments for interpreting these results with caution are presented based on risk of bias. Limitations of the evidence are discussed, such confounding variables and lack of statistical power., Conclusion: The evidence base for the impact of HSCT for MS on neuropsychological outcomes is limited. Further research is required to progress understanding to facilitate clinician and patient understanding of HSCT treatment for MS., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. No known declarations of interest to state., (Copyright © 2024. Published by Elsevier B.V.)
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- 2024
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28. Exosome Content-Mediated Signaling Pathways in Multiple Sclerosis.
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Mohammadinasr M, Montazersaheb S, Ayromlou H, Hosseini V, Molavi O, and Hejazi MS
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- Humans, Animals, MicroRNAs metabolism, MicroRNAs genetics, Exosomes metabolism, Multiple Sclerosis metabolism, Multiple Sclerosis pathology, Multiple Sclerosis therapy, Signal Transduction
- Abstract
Exosomes are small extracellular vesicles with a complex lipid-bilayer surface and 30-150 nm diameter. These vesicles play a critical role in intercellular signaling networks during physiopathological processes through data trafficking and cell reprogramming. It has been demonstrated that exosomes are involved in a variety of central nervous system (CNS) disorders such as multiple sclerosis (MS). Exosome mediators' cell-to-cell communication is possibly by delivering their contents such as proteins, RNAs (coding and non-coding), DNAs (mitochondrial and genomic), and transposable elements to the target cells. Exosomal microRNAs (miRNAs) differ in their expression patterns in MS disease, thereby providing novel diagnostic and prognostic biomarkers and therapeutic options for better treatment of MS disease. Furthermore, these microvesicles are non-immunogenic and non-toxic therapeutic tools for transferring miRNAs across the blood-brain barrier (BBB). Collectively, exosomes could be used as novel drug delivery devices for the treatment of MS patients. This review summarized research regarding the exosomes from serum, plasma, PBMC, and other cells in MS patients and experimental models. We also provide a critical view of exosome content-mediated signaling pathways in MS, including TNF-α, TGF-β, NF-κB, and Wnt pathways. The use of exosomes as a therapeutic potential in MS has also been discussed., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
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- 2024
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29. Nurse-led immunotreatment DEcision Coaching In people with Multiple Sclerosis (DECIMS) - A cluster- randomised controlled trial and mixed methods process evaluation.
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Rahn AC, Peper J, Köpke S, Antony G, Liethmann K, Vettorazzi E, and Heesen C
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- Humans, Female, Male, Adult, Germany, Middle Aged, Mentoring methods, Cluster Analysis, Multiple Sclerosis therapy, Decision Making
- Abstract
Objective: To evaluate a nurse-led decision coaching programme aiming to redistribute health professionals' tasks to support immunotherapy decision-making in people with multiple sclerosis (MS)., Methods: Cluster-randomised controlled trial with an accompanying mixed methods process evaluation (2014 - 2018). We planned to recruit 300 people with clinically isolated syndrome or relapsing-remitting MS facing immunotherapy decisions in 15 clusters across Germany. Participants in the intervention clusters received up to three decision coaching sessions by a trained nurse and access to an evidence-based online information platform. In the control clusters, participants also had access to the information platform. The primary outcome was informed choice after six months, defined as good risk knowledge and congruent attitude and uptake., Results: Twelve nurses from eight clusters participated in the decision coaching training. Due to insufficient recruitment, the randomised controlled trial was terminated prematurely with 125 participants (n = 42 intervention clusters, n = 83 control clusters). We found a non-significant difference between groups for informed choice favouring decision coaching: odds ratio 1.64 (95% CI 0.49-5.53)., Conclusions: Results indicate that decision coaching might facilitate informed decision-making in MS compared to providing patient information alone., Practice Implications: Barriers have to be overcome to achieve structural change and successful implementation., Competing Interests: Declaration of Competing Interest AR, EV, SK, GA, KL and JP declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. CH declares the following financial interests/personal relationships which may be considered as potential competing interests: CH has received research grants from Merck, Novartis and Roche., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
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- 2024
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30. Neutrophil to lymphocyte ratio and systemic immune-inflammatory index as markers of response to autologous hematopoietic stem cell transplantation in persons with multiple sclerosis.
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Ocaña-Ramm G, Gallardo-Pérez MM, Garcés-Eisele SJ, Sánchez-Bonilla D, Robles-Nasta M, Hernández-Flores EJ, Hamilton-Avilés LE, Negrete-Rodríguez P, Melgar-de-la-Paz M, Lira-Lara O, Olivares-Gazca JC, Ruiz-Delgado GJ, and Ruiz-Argüelles GJ
- Subjects
- Humans, Female, Male, Adult, Middle Aged, Inflammation blood, Lymphocyte Count, Hematopoietic Stem Cell Transplantation, Neutrophils, Multiple Sclerosis therapy, Multiple Sclerosis blood, Transplantation, Autologous, Lymphocytes, Biomarkers blood
- Abstract
Introduction: Biomarkers that help to evaluate the immune system and could be useful in multiple sclerosis (MS) are the neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and systemic immune-inflammatory index (SII). The objective of this work is to evaluate the significance of the SII index, PLR, and NLR before and after transplantation in individuals with MS who underwent autologous hematopoietic stem cell transplant (aHSCT) at a single institution., Methods: Patients with MS who received an aHSCT between 2017 and 2022 were included in the study. NLR, PLR, and SII index were calculated prior to the transplant and 100 days after, and evaluation of the expanded disability status scale (EDSS) was done before the transplant and 12 months after. The cohort was divided into two groups: aHSCT responders (R) and nonresponders (NR)., Results: Fifty-eight individuals were examined: 37 patients in the responders group R group and 21 in NR group. There was no statistically significant difference in the SII, NLR, and PLR prior to the transplant, however at 100 days post-HSCT, NLR in the R group was 1.8 versus 3.1 in the NR group (p = 0.003), PLR was 194 versus 295, respectively (p = 0.024), meanwhile SII index was 489.5 versus 729.3 (p < 0.001)., Conclusion: High NLR and SII index values after the aHSCT were associated with a worsening in the EDSS score. However, since this is the first ever study that compared NLR and SII index with the aHSCT response in persons with MS, further studies must be performed to corroborate this information., (© 2024 John Wiley & Sons Ltd.)
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- 2024
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31. Intermittent and periodic fasting - Evidence and perspectives in multiple sclerosis.
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Lorefice L, Pitzalis M, and Zoledziewska M
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- Humans, Animals, Multiple Sclerosis therapy, Fasting physiology
- Abstract
Multiple sclerosis (MS) is a complex neurological disease characterized by great variability in clinical presentation, including the radiological features, and degree of disability. Both genetics and environment contribute to disease etiopathogenesis. Because MS is more common in Western countries, and diet has been proposed among the etiologic factors. However, based on the several studies published thus far, principally involving small cohorts, there is no described diet-protocol to be applied in clinical practice as a supplement to the standard immunomodulatory treatment of MS. Diet is an easily changeable factor thus the research on the diet importance in MS has been exploded in last years. Starting from the notions that diet can change lifespan and quality of life in general, and its improvement could be one of many contributing factors with effects on disease evolution, this review examines the evidence of the effects of intermittent fasting in a mouse model of MS; the evidence derived from clinical trials; and future perspectives., Competing Interests: Declaration of competing interest Lorefice Lorena received honoraria for consultancy or speaking from Biogen, Novartis, Sanofi Genzyme, Serono and Teva and Almirall. Pitzalis Maristella and Zoledziewska Magdalena have nothing to disclose., (Copyright © 2024 Elsevier B.V. All rights reserved.)
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- 2024
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32. Perspectives on fatigue management among veterans living with multiple sclerosis.
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Knowles LM, Yang B, Mata-Greve F, and Turner AP
- Subjects
- Humans, Male, Middle Aged, Female, Adult, Aged, Qualitative Research, Veterans, Multiple Sclerosis complications, Multiple Sclerosis therapy, Multiple Sclerosis rehabilitation, Telemedicine, Cognitive Behavioral Therapy methods, Fatigue therapy, Fatigue etiology, Fatigue rehabilitation
- Abstract
Background: Chronic fatigue is one of the most common, disabling, and least understood symptoms of many chronic health conditions including multiple sclerosis (MS). A multidisciplinary rehabilitative treatment approach is recommended for MS-related fatigue, but few people with MS have access to such treatment. In-person and telehealth cognitive behavioral therapy (CBT) for fatigue is an emerging acceptable and effective treatment for MS-related fatigue in civilians that has not been studied in Veterans with MS, a population that is more likely to be older, male, unemployed, and disabled. The present study aimed to understand how Veterans with MS (1) describe their fatigue and (2) manage their fatigue, and (3) perceive telehealth CBT for MS-related fatigue., Method: Twenty-four Veterans with MS completed semi-structured interviews and a brief survey. For descriptive purposes, the survey included questionnaires on demographics, fatigue, psychosocial functioning, depression, and pain. Thematic analysis with a combined deductive and inductive approach was used to analyze interview transcripts., Results: Three themes emerged. First, "experience of MS fatigue as 'one big tapestry'" described fatigue as deficits in physical and mental energy that were fluctuating and complex in their interaction with biological factors. Veterans described that MS fatigue negatively impacted daily activities of living, emotions, and cognitive functioning. Second, "managing MS fatigue through trial and error" revealed that Veterans expend significant time and effort learning and trialing fatigue management strategies based on their personal beliefs, military training/experiences, provider recommendations, and iterative learning. Most Veterans described energy management, relaxation, exercise, and adaptive thinking as helpful for managing fatigue. Interestingly, the helpfulness of medication for fatigue was highly variable, and none of the Veterans described medication as a standalone fatigue treatment. The third theme, "practicing flexibility with telehealth CBT for MS fatigue" revealed Veteran's enthusiasm about telehealth CBT for MS-related fatigue and highlighted the importance of flexible delivery to meet individual needs., Conclusion: Veteran participants shared their experience of MS-related fatigue as well as management strategies that are consistent with previous research in civilians with MS fatigue. Notably, Veterans' preference for flexible nonpharmacological intervention can inform adaptation of telehealth CBT for Veterans with MS fatigue., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier B.V.)
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- 2024
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33. Unleashing the power of anti-CD20 immunotherapy: Mitigating multiple sclerosis risk in Epstein-Barr virus latent infections.
- Author
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Alrashoudi RH
- Subjects
- Humans, Latent Infection immunology, Herpesvirus 4, Human immunology, Rituximab therapeutic use, Rituximab adverse effects, Multiple Sclerosis immunology, Multiple Sclerosis drug therapy, Multiple Sclerosis therapy, Multiple Sclerosis virology, Epstein-Barr Virus Infections immunology, Epstein-Barr Virus Infections therapy, Epstein-Barr Virus Infections complications, Antigens, CD20 immunology, Immunotherapy methods
- Abstract
Multiple sclerosis (MS) is a chronic inflammatory, demyelinating, and neurodegenerative connective tissue disease affecting the central nervous system (CNS). Recently, there has been a dramatic improvement in several vital concepts of immune pathophysiology underlying MS. Notably, one of the prerequisites to MS development is Epstein-Barr virus (EBV) infection. Greater attention has been drawn towards promising, innovative immunotherapies in the management and treatment of MS. Whilst there are numerous immunotherapies currently proposed for MS, the B cell depleting therapy that predominantly uses the anti-CD20 monoclonal antibodies (mAbs) such as rituximab, ocrelizumab, and ofatumumab have demonstrated promising clinical benefits by targeting the memory B cells, which are the primary reservoir of EBV latency. Although mAbs have proved beneficial in the treatment of MS, they pose the risk of potential adverse effects. The current systematic review was undertaken to explore the therapeutic role of anti-CD20 therapy and its downsides in the treatment of MS and EBV infection. Clinical trials and prospective and retrospective studies reporting anti-CD20 therapy were carefully reviewed. The initial sections discuss the clinical features of MS, the probable link between EBV and MS, and the role of B cells in MS pathogenesis. Here, we show the potential role of anti-CD20 therapy more of a boon than a bane as the therapy yields more promising results for MS treatment. Nevertheless, the adverse effects could be minimized following a planned therapeutic regimen for treating MS patients.
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- 2024
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34. [Neuro-urological diagnostics and treatment of non-traumatic/degenerative neurogenic lower urinary tract dysfunction exemplified by multiple sclerosis].
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Kurze I and Jaekel AK
- Subjects
- Humans, Multiple Sclerosis complications, Multiple Sclerosis diagnosis, Multiple Sclerosis therapy, Urinary Bladder, Neurogenic diagnosis, Urinary Bladder, Neurogenic therapy, Urinary Bladder, Neurogenic etiology, Lower Urinary Tract Symptoms etiology, Lower Urinary Tract Symptoms diagnosis, Lower Urinary Tract Symptoms therapy
- Abstract
Neurogenic lower urinary tract dysfunction in multiple sclerosis is often underestimated, underdiagnosed, and inadequately treated. Depending on the course of the disease and the location of neural damage, it occurs with varying frequency and types of impairment of urine storage and voiding function. Symptoms such as urinary incontinence, recurrent urinary tract infections, urgency, pollakiuria, reduced urinary flow, hesitancy as well as postvoid residual urine may occur. However, the symptoms do not allow any conclusions to be drawn about the underlying type of neurogenic lower urinary tract dysfunction. Although numerous data, publications, and guidelines are available on this topic today, there continues to be a lack of standardized screening parameters and algorithms that have been tested in prospective studies for multiple sclerosis. This article presents the current diagnostic and therapeutic options of neurogenic lower urinary tract dysfunction in multiple sclerosis. A crucial issue is the initial delay in diagnosis, not least due to a lack of communication between neurologists and urologists. Initial indicators of the presence of neurogenic lower urinary tract dysfunction can be obtained by actively asking about the subjective presence of symptoms such as urinary incontinence or the occurrence of urinary tract infections. However, a subjective lack of symptoms does not rule out a neurogenic lower urinary tract dysfunction. Regardless of the stage of the disease, an early and individualized neuro-urological diagnosis and treatment should be implemented. All aspects of the damage and the extent of functional deficits in other organ systems caused by multiple sclerosis must be included in this neuro-urological treatment decision, which requires a consistent interdisciplinary exchange between neurologists, general practitioners, and urologists. This interdisciplinary and interprofessional way of thinking and acting is key for an optimal treatment using the numerous therapeutic procedures. Lifelong, individual, risk-adapted urological care for the early detection and prevention of neuro-urological complications should be offered to persons with multiple sclerosis., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)
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- 2024
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35. Intraperitoneal injection of mesenchymal stem cells-conditioned media (MSCS-CM) treated monocyte can potentially alleviate motor defects in experimental autoimmune encephalomyelitis female mice; An original experimental study.
- Author
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Jalali Kondori B, Abdolmaleki A, Raei M, Ghorbani Alvanegh A, and Esmaeili Gouvarchin Ghaleh H
- Subjects
- Animals, Female, Mice, Culture Media, Conditioned pharmacology, Injections, Intraperitoneal, Monocytes immunology, Guinea Pigs, Cytokines metabolism, Cells, Cultured, Mesenchymal Stem Cell Transplantation, Multiple Sclerosis therapy, Multiple Sclerosis immunology, Macrophages immunology, Macrophages metabolism, Disease Models, Animal, Humans, Encephalomyelitis, Autoimmune, Experimental therapy, Encephalomyelitis, Autoimmune, Experimental immunology, Mice, Inbred C57BL, Mesenchymal Stem Cells metabolism
- Abstract
Introduction: Multiple sclerosis (MS), as a destructive pathology of myelin in central nervous system (CNS), causes physical and mental complications. Experimental autoimmune encephalomyelitis (EAE) is laboratory model of MS widely used for CNS-associated inflammatory researches. Cell therapy using macrophage M2 (MPM2) is a cell type with anti-inflammatory characteristics for all inflammatory-based neuropathies. This experimental study investigated the probable therapeutic anti-inflammatory effects of intraperitoneal (IP) injection of MPM2 on alleviation of motor defect in EAE-affected animals., Materials and Methods: 24 C57/BL6 female mice were divided into four groups of EAE, EAE + Dexa, EAE + PBS, and EAE + MP2. EAE was induced through deep cervical injection of spinal homogenate of guinea pigs. MPM2 cells were harvested from bone marrow and injected (10
6 cells/ml) in three days of 10, 13 and 16 post-immunizations (p.i). Clinical score (CS), anti-inflammatory cytokines (IL-4, IL-10), pro-inflammatory gene expression (TNF-α, IL-1β) and histopathological investigations (HE, Nissl and Luxol Fast Blue) were considered. Data were analyzed using SPSS software (v.19) and p < 0.05 was considered significant level., Results: During EAE induction, the mean animal weight was decreased (p < 0.05); besides, following MPM2 injection, the weight gain was applied (p < 0.05) in EAE + MPM2 groups than control. Increased (p < 0.05) levels of CS was found during EAE induction in days 17-28 in EAE animals; besides, CS was decreased (p < 0.05) in EAE + MPM2 group than EAE animals. Also, in days 25-28 of experiment, the CS was decreased (p < 0.05) in EAE + MPM2 than EAE + Dexa. Histopathological assessments revealed low density of cell nuclei in corpus callosum, microscopically. LFB staining also showed considerable decrease in white matter density of corpus callosum in EAE group. Acceleration of white matter density was found in EAE + MPM2 group following cell therapy procedure. Genes expression of TNF-α, IL-1β along with IL-4 and IL-10 were decreased (p < 0.05) in EAE + MPM2 group., Conclusion: IP injection of MPM2 to EAE-affected female mice can potentially reduce the CNS inflammation, neuronal death and myelin destruction. MPM2 cell therapy can improve animal motor defects., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024. Published by Elsevier B.V.)- Published
- 2024
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36. Involvement of gut microbiota in multiple sclerosis-review of a new pathophysiological hypothesis and potential treatment target.
- Author
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Olejnik P, Buczma K, Cudnoch-Jędrzejewska A, and Kasarełło K
- Subjects
- Humans, Animals, Blood-Brain Barrier immunology, Blood-Brain Barrier metabolism, Fatty Acids, Volatile metabolism, Gastrointestinal Microbiome immunology, Multiple Sclerosis immunology, Multiple Sclerosis microbiology, Multiple Sclerosis therapy, Dysbiosis immunology, Probiotics therapeutic use, Probiotics administration & dosage, Fecal Microbiota Transplantation
- Abstract
Multiple sclerosis (MS) is a chronic inflammatory disease that leads to demyelination and damage to the central nervous system. It is well known, the significance of the involvement and influence of the immune system in the development and course of MS. Nowadays, more and more studies are demonstrating that an important factor that affects the action of the immune system is the gut microbiota. Changes in the composition and interrelationships in the gut microbiota have a significant impact on the course of MS. Dysbiosis affects the disease course mainly by influencing the immune system directly but also by modifying the secreted metabolites and increasing mucosal permeability. The essential metabolites affecting the course of MS are short-chain fatty acids, which alter pro- and anti-inflammatory responses in the immune system but also increase the permeability of the intestinal wall and the blood-brain barrier. Dietary modification alone can have a significant impact on MS. Based on these interactions, new treatments for MS are being developed, including probiotics administration, supplementation of bacterial metabolites, fecal microbiota transplantation, and dietary changes. Further studies may serve to develop new drugs and therapeutic approaches for MS., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
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- 2024
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37. The effect of education of self-care behaviors on the quality of life and resilience of multiple sclerosis patients.
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Rakhshani T, Afroozeh S, Kashfi SM, Kamyab A, and Khani Jeihooni A
- Subjects
- Humans, Adult, Male, Female, Middle Aged, Young Adult, Adolescent, Iran epidemiology, Quality of Life psychology, Multiple Sclerosis psychology, Multiple Sclerosis therapy, Multiple Sclerosis epidemiology, Self Care methods, Self Care psychology, Resilience, Psychological, Patient Education as Topic methods
- Abstract
Background: Multiple sclerosis (MS) is one of the most common causes of non-traumatic disability in young adults. Typically, doctors diagnose MS between the ages of 20 and 50. This study aims to determine the effect of educational intervention on self-care behaviors on MS patients' quality of life and resilience in Shiraz, Iran., Methods: This interventional study included 90 individuals, aged 15 to 50, who were members of the support association for MS patients in Shiraz city, Iran. The study employed a convenient sampling method. Patients were randomly assigned to two experimental and control groups, and the self-care educational program was conducted during six educational sessions. The quality of life and resilience of the patients were measured before and after the study. Information was collected by completing the questionnaires before and three months after the intervention. To analyze the data, SPSS 23 was used. To describe the data, frequency, percentage, mean, and standard deviation indicators were used, and for analysis, independent t-tests and paired t-tests were used., Results: This study examined a total of 90 MS patients. 50.4% of the people in the study were married, 40% of them had a high school diploma, and 78.5% were unemployed. The results of the t-test showed that there was a significant difference between all the components of self-care, quality of life, and resilience before and after the intervention (P < 0.05)., Conclusion: By accepting the responsibility of self-care, patients would improve the inadequacies and disabilities resulting from the disease, use the power of self-care to solve problems, and improve their quality of life and resilience., (© 2024. The Author(s).)
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- 2024
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38. [Theoretical approach and prognostic significance of high disease activity in multiple sclerosis].
- Author
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Mátyás K
- Subjects
- Humans, Prognosis, Inflammation, Multiple Sclerosis therapy, Multiple Sclerosis diagnosis, Multiple Sclerosis immunology, Disease Progression
- Abstract
Multiple sclerosis (MS) is an autoimmune inflammatory disease of the central nervous system with demyelination and neurodegeneration. In addition to the inflammatory immune processes that characterise the onset of the disease with relapses, chronic inflammation is also present from the onset of the disease. The catabolic processes induced by chronic inflammation are responsible for the axonal degeneration that causes the progression of the disease. The activity of the disease is well defined, an important prognostic factor, and a determining factor in the indication of disease-modifying therapies. It is important to establish disease activity at the time of diagnosis and to monitor it continuously during patient care, both clinically and radiologically, as it is the basis for deciding on the current treatment. If detected on the basis of the professional guideline, it is necessary to start or switch to a highly effective therapy.
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- 2024
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39. The Role of Intestinal Microbiota and Probiotics Supplementation in Multiple Sclerosis Management.
- Author
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Hasaniani N, Mostafa Rahimi S, Akbari M, Sadati F, Pournajaf A, and Rostami-Mansoor S
- Subjects
- Humans, Brain-Gut Axis physiology, Brain-Gut Axis drug effects, Animals, Dietary Supplements, Probiotics administration & dosage, Probiotics therapeutic use, Multiple Sclerosis microbiology, Multiple Sclerosis therapy, Gastrointestinal Microbiome physiology
- Abstract
Multiple sclerosis (MS) is a neurological autoimmune disorder predominantly afflicting young adults. The etiology of MS is intricate, involving a variety of environmental and genetic factors. Current research increasingly focuses on the substantial contribution of gut microbiota in MS pathogenesis. The commensal microbiota resident within the intestinal milieu assumes a central role within the intricate network recognized as the gut-brain axis (GBA), wielding beneficial impact in neurological and psychological facets. As a result, the modulation of gut microbiota is considered a pivotal aspect in the management of neural disorders, including MS. Recent investigations have unveiled the possibility of using probiotic supplements as a promising strategy for exerting a positive impact on the course of MS. This therapeutic approach operates through several mechanisms, including the reinforcement of gut epithelial integrity, augmentation of the host's resistance against pathogenic microorganisms, and facilitation of mucosal immunomodulatory processes. The present study comprehensively explains the gut microbiome's profound influence on the central nervous system (CNS). It underscores the pivotal role played by probiotics in forming the immune system and modulating neurotransmitter function. Furthermore, the investigation elucidates various instances of probiotic utilization in MS patients, shedding light on the potential therapeutic advantages afforded by this intervention., (Copyright © 2024 IBRO. Published by Elsevier Inc. All rights reserved.)
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- 2024
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40. [XVI Post-ECTRIMS Meeting: review of the new developments presented at the 2023 ECTRIMS Congress (II)].
- Author
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Fernández O, Montalbán X, Agüera E, Aladro Y, Alonso A, Arroyo R, Brieva L, Calles C, Costa-Frossard L, Eichau S, García-Domínguez JM, Hernández MA, Landete L, Llaneza M, Llufriu S, Meca-Lallana JE, Meca-Lallana V, Moral E, Prieto JM, Ramió-Torrentà L, Téllez N, Romero-Pinel L, Vilaseca A, and Rodríguez-Antigüedad A
- Subjects
- Aged, Female, Humans, Male, Congresses as Topic, Multiple Sclerosis therapy
- Abstract
The XVI Post-ECTRIMS meeting was held in Seville on 20 and 21 October 2023, where expert neurologists in multiple sclerosis (MS) summarised the main new developments presented at the ECTRIMS 2023 congress, which took place in Milan from 11 to 13 October. The aim of this article is to summarise the content presented at the Post-ECTRIMS Meeting, in an article in two parts. This second part covers the health of women and elderly MS patients, new trends in the treatment of cognitive impairment, focusing particularly on meditation, neuroeducation and cognitive rehabilitation, and introduces the concept of fatigability, which has been used to a limited extent in MS. The key role of digitalization and artificial intelligence in the theoretically near future is subject to debate, along with the potential these technologies can offer. The most recent research on the various treatment algorithms and their efficacy and safety in the management of the disease is reviewed. Finally, the most relevant data for cladribine and evobrutinib are presented, as well as future therapeutic strategies currently being investigated.
- Published
- 2024
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41. Re-establishing immune tolerance in multiple sclerosis: focusing on novel mechanisms of mesenchymal stem cell regulation of Th17/Treg balance.
- Author
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Hu H, Li H, Li R, Liu P, and Liu H
- Subjects
- Humans, Animals, Mesenchymal Stem Cell Transplantation, Th17 Cells immunology, T-Lymphocytes, Regulatory immunology, Mesenchymal Stem Cells immunology, Multiple Sclerosis immunology, Multiple Sclerosis therapy, Immune Tolerance
- Abstract
The T-helper 17 (Th17) cell and regulatory T cell (Treg) axis plays a crucial role in the development of multiple sclerosis (MS), which is regarded as an immune imbalance between pro-inflammatory cytokines and the maintenance of immune tolerance. Mesenchymal stem cell (MSC)-mediated therapies have received increasing attention in MS research. In MS and its animal model experimental autoimmune encephalomyelitis, MSC injection was shown to alter the differentiation of CD4
+ T cells. This alteration occurred by inducing anergy and reduction in the number of Th17 cells, stimulating the polarization of antigen-specific Treg to reverse the imbalance of the Th17/Treg axis, reducing the inflammatory cascade response and demyelination, and restoring an overall state of immune tolerance. In this review, we summarize the mechanisms by which MSCs regulate the balance between Th17 cells and Tregs, including extracellular vesicles, mitochondrial transfer, metabolic reprogramming, and autophagy. We aimed to identify new targets for MS treatment using cellular therapy by analyzing MSC-mediated Th17-to-Treg polarization., (© 2024. The Author(s).)- Published
- 2024
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42. Targeted DeSUMOylation as a therapeutic strategy for multiple sclerosis.
- Author
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Sriram S, Kim KW, and Ljunggren-Rose Å
- Subjects
- Animals, Humans, Encephalomyelitis, Autoimmune, Experimental drug therapy, Encephalomyelitis, Autoimmune, Experimental immunology, Encephalomyelitis, Autoimmune, Experimental metabolism, Multiple Sclerosis drug therapy, Multiple Sclerosis immunology, Multiple Sclerosis therapy, Multiple Sclerosis metabolism, Sumoylation drug effects
- Abstract
SUMO (small ubiquitin like modifier) conjugated proteins have emerged as an important post translational modifier of cellular function. SUMOylation modulates several cellular processes involved in transcriptional regulation of genes, protein-protein interactions and DNA damage and repair. Since abnormalities in SUMOylation has been observed in neoplastic and neurodegenerative disorders, the SUMO pathway has become an attractive site for targeting of new therapies to regulate SUMOylation and reduce disease burden. Conjugation of SUMO to their respective substrates is orchestrated by an enzymatic cascade involving three main enzymes, E1, activation enzyme, E2, conjugating enzyme and E3, a protein ligase. Each of these enzymes are therefore potential "druggable" sites for future therapeutics. SUMOylation is a well-known mechanism by which the innate immune response is regulated in response to viral infections and in the adaptive immune response to tumor immunity. We have shown that small molecules which inhibit the SUMO activation pathway are also capable of inhibiting autoimmune response. TAK981 which forms adducts with SUMO and anacardic acid which inhibits the E1 enzyme of the SUMO pathway were effective in preventing the development of experimental allergic encephalitis (EAE), a mouse model of multiple sclerosis. Anacardic acid and TAK981 inhibited activation of TH17 cells and reduced clinical and pathological injury in IL-17 mediated myelin oligodendrocyte glycoprotein (MOG) induced EAE. Ginkgolic acid, another known inhibitor of SUMO pathway, was also shown to be effective in reducing the severity of inflammatory arthropathies which is also IL-17 mediated. In addition, the increase in the transcription of myelin genes with TAK981 and anacardic acid improved remyelination in experimental models of demyelination. In the present review paper, we examine the mechanism of action of inhibitors of the SUMO pathway on regulating the immune response and the possibility of the use of these agents as therapeutics for MS., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
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- 2024
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43. High-intensity interval training improves bone remodeling, lipid profile, and physical function in multiple sclerosis patients.
- Author
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Amato A, Proia P, Alioto A, Rossi C, Pagliaro A, Ragonese P, Schirò G, Salemi G, Caldarella R, Vasto S, Nowak R, Kostrzewa-Nowak D, Musumeci G, and Baldassano S
- Subjects
- Humans, Male, Female, Adult, Lipids blood, Lipid Metabolism, Biomarkers blood, Middle Aged, Quality of Life, Exercise Therapy methods, Exercise physiology, High-Intensity Interval Training methods, Multiple Sclerosis physiopathology, Multiple Sclerosis blood, Multiple Sclerosis therapy, Bone Remodeling
- Abstract
Multiple sclerosis (MS) is a demyelinating and neurodegenerative disease due to an autoimmune chronic inflammatory response, yet the etiology is currently not completely understood. It is already known that physical activity plays an essential role in improving quality of life, especially in neuropathological conditions. The study was aimed to investigate the possible benefits of high-intensity interval training (HIIT) in bone and lipid metabolism markers, and neuromotor abilities in MS patients. 130 participants were recruited; 16 subjects with MS met the inclusion criteria and were included in the data analysis. The patients were randomly assigned to two groups: a Control group (CG) (34.88 ± 4.45 yrs) that didn't perform any physical activity and the Exercise group (EG) (36.20 ± 7.80 yrs) that performed HIIT protocol. The training program was conducted remotely by a kinesiologist. It was performed three times a week for 8 weeks. At the beginning (T0) and the end of the study (T1) physical function tests, bone remodelling markers, and lipid markers analyses were performed. After 8 weeks of training the wall squat (s) (T0 = 27.18 ± 4.21; T1 = 41.68 ± 5.38, p ≤ 0.01) and Time Up and Go test (s) (T0 = 7.65 ± 0.43; T1 = 6.34 ± 0.38 p ≤ 0.01) performances improved; lipid markers analysis showed a decrease in Total (mg/dl) (T0 = 187.22 ± 15.73; T1 = 173.44 ± 13.03, p ≤ 0.05) and LDL (mg/dl) (T0 = 108 ± 21.08; T1 = 95.02 ± 17.99, p < 0.05) cholesterol levels. Additionally, the levels of osteocalcin (µg/L), a marker of bone formation increased (T0 = 20.88 ± 4.22; T1 = 23.66 ± 6.24, p < 0.05), 25-OH Vitamin D (µg/L) improved after 8 weeks (T0 = 21.11 ± 7.11; T1 = 27.66 ± 7.59, p < 0.05). HIIT had an effect on lower limb strength and gait control, improved bone formation, and lipid management, in MS patients., (© 2024. The Author(s).)
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- 2024
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44. The interplay of inflammation and remyelination: rethinking MS treatment with a focus on oligodendrocyte progenitor cells.
- Author
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Zveik O, Rechtman A, Ganz T, and Vaknin-Dembinsky A
- Subjects
- Humans, Animals, Cell Differentiation physiology, Myelin Sheath, Oligodendroglia, Remyelination physiology, Multiple Sclerosis immunology, Multiple Sclerosis therapy, Multiple Sclerosis pathology, Oligodendrocyte Precursor Cells, Inflammation immunology
- Abstract
Background: Multiple sclerosis (MS) therapeutic goals have traditionally been dichotomized into two distinct avenues: immune-modulatory-centric interventions and pro-regenerative strategies. Oligodendrocyte progenitor cells (OPCs) were regarded for many years solely in concern to their potential to generate oligodendrocytes and myelin in the central nervous system (CNS). However, accumulating data elucidate the multifaceted roles of OPCs, including their immunomodulatory functions, positioning them as cardinal constituents of the CNS's immune landscape., Main Body: In this review, we will discuss how the two therapeutic approaches converge. We present a model by which (1) an inflammation is required for the appropriate pro-myelinating immune function of OPCs in the chronically inflamed CNS, and (2) the immune function of OPCs is crucial for their ability to differentiate and promote remyelination. This model highlights the reciprocal interactions between OPCs' pro-myelinating and immune-modulating functions. Additionally, we review the specific effects of anti- and pro-inflammatory interventions on OPCs, suggesting that immunosuppression adversely affects OPCs' differentiation and immune functions., Conclusion: We suggest a multi-systemic therapeutic approach, which necessitates not a unidimensional focus but a harmonious balance between OPCs' pro-myelinating and immune-modulatory functions., (© 2024. The Author(s).)
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- 2024
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45. Electrical stimulation of the vagus nerve ameliorates inflammation and disease activity in a rat EAE model of multiple sclerosis.
- Author
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Natarajan C, Le LHD, Gunasekaran M, Tracey KJ, Chernoff D, and Levine YA
- Subjects
- Animals, Rats, Inflammation therapy, Inflammation pathology, Disease Models, Animal, Female, Myelin Sheath metabolism, Blood-Brain Barrier, Encephalomyelitis, Autoimmune, Experimental therapy, Encephalomyelitis, Autoimmune, Experimental immunology, Multiple Sclerosis therapy, Multiple Sclerosis immunology, Multiple Sclerosis pathology, Vagus Nerve, Vagus Nerve Stimulation methods
- Abstract
Multiple sclerosis (MS) is a demyelinating central nervous system (CNS) disorder that is associated with functional impairment and accruing disability. There are multiple U.S. Food and Drug Administration (FDA)-approved drugs that effectively dampen inflammation and slow disability progression. However, these agents do not work well for all patients and are associated with side effects that may limit their use. The vagus nerve (VN) provides a direct communication conduit between the CNS and the periphery, and modulation of the inflammatory reflex via electrical stimulation of the VN (VNS) shows efficacy in ameliorating pathology in several CNS and autoimmune disorders. We therefore investigated the impact of VNS in a rat experimental autoimmune encephalomyelitis (EAE) model of MS. In this study, VNS-mediated neuroimmune modulation is demonstrated to effectively decrease EAE disease severity and duration, infiltration of neutrophils and pathogenic lymphocytes, myelin damage, blood-brain barrier disruption, fibrinogen deposition, and proinflammatory microglial activation. VNS modulates expression of genes that are implicated in MS pathogenesis, as well as those encoding myelin proteins and transcription factors regulating new myelin synthesis. Together, these data indicate that neuroimmune modulation via VNS may be a promising approach to treat MS, that not only ameliorates symptoms but potentially also promotes myelin repair (remyelination)., Competing Interests: Competing interests statement:C.N., L.H.D.L., D.C., and Y.A.L. are employees of SetPoint Medical. M.G. was an employee of SetPoint Medical when the work was performed. C.N., K.J.T., D.C., and Y.A.L. own options/shares of SetPoint Medical. C.N., M.G., K.J.T., D.C., and Y.A.L. are named inventors on patent filings relevant to the methods discussed in this paper.
- Published
- 2024
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46. Current Knowledge about Nonclassical Monocytes in Patients with Multiple Sclerosis, a Systematic Review.
- Author
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Arneth B
- Subjects
- Humans, Encephalomyelitis, Autoimmune, Experimental immunology, Encephalomyelitis, Autoimmune, Experimental pathology, Biomarkers, Animals, Disease Progression, Monocytes immunology, Monocytes metabolism, Multiple Sclerosis pathology, Multiple Sclerosis immunology, Multiple Sclerosis therapy, Multiple Sclerosis metabolism
- Abstract
Monocytes play a critical role in the initiation and progression of multiple sclerosis (MS). Recent research indicates the importance of considering the roles of monocytes in the management of MS and the development of effective interventions. This systematic review examined published research on the roles of nonclassical monocytes in MS and how they influence disease management. Reputable databases, such as PubMed, EMBASE, Cochrane, and Google Scholar, were searched for relevant studies on the influence of monocytes on MS. The search focused on studies on humans and patients with experimental autoimmune encephalomyelitis (EAE) published between 2014 and 2024 to provide insights into the study topic. Fourteen articles that examined the role of monocytes in MS were identified; the findings reported in these articles revealed that nonclassical monocytes could act as MS biomarkers, aid in the development of therapeutic interventions, reveal disease pathology, and improve approaches for monitoring disease progression. This review provides support for the consideration of monocytes when researching effective diagnostics, therapeutic interventions, and procedures for managing MS pathophysiology. These findings may guide future research aimed at gaining further insights into the role of monocytes in MS.
- Published
- 2024
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47. Healthcare resource utilization and economic burden of multiple sclerosis in Chinese patients: results from a real-world survey.
- Author
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Sun C, Jia Y, Li H, Qiao X, Tang M, Geng M, Jones E, Pike J, Unsworth M, and Hu M
- Subjects
- Humans, China epidemiology, Female, Male, Adult, Middle Aged, Cross-Sectional Studies, Patient Acceptance of Health Care statistics & numerical data, Health Resources economics, Health Resources statistics & numerical data, Surveys and Questionnaires, Hospitalization economics, Severity of Illness Index, East Asian People, Multiple Sclerosis economics, Multiple Sclerosis therapy, Cost of Illness, Health Care Costs
- Abstract
Multiple sclerosis (MS) is uncommon in China and the standard of care is underdeveloped, with limited utilization of disease-modifying treatment (DMT). An understanding of real-world disease burden (including direct medical, non-medical, and indirect costs, such as loss of productivity), is currently lacking in this population. To investigate the overall burden of managing patients with MS in China, a cross-sectional survey of physicians and their consulting patients with MS was conducted in 2021. Physicians provided information on healthcare resource utilization (HCRU; consultations, hospitalizations, tests, medication) and associated costs. Patients provided data on changes in their life, productivity, and impairment of daily activities due to MS. Results were stratified by disease severity using generalized linear models, with a p value < 0.05 considered statistically significant. Patients with more severe disease had greater HCRU, including hospitalizations, consultations and tests/scans, and incurred higher direct and indirect costs and productivity loss, compared with those with milder disease. However, the use of DMT was higher in patients with mild disease severity. With the low uptake and limited efficacy of non-DMT drugs, Chinese patients with MS experience a high disease burden and significant unmet needs. Therapeutic interventions could help save downstream costs and lessen societal burden., (© 2024. The Author(s).)
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- 2024
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48. Diversity and inclusion in behavioural intervention trials in multiple sclerosis: A commentary.
- Author
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Sidhu NK, Proudfoot H, Adan HM, Fawson S, and Moss-Morris R
- Subjects
- Humans, Patient Selection, Behavior Therapy methods, Clinical Trials as Topic, Cultural Diversity, Multiple Sclerosis therapy
- Abstract
Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article.
- Published
- 2024
- Full Text
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49. No one really plans to have multiple sclerosis: Transition readiness and quality of life in paediatric multiple sclerosis.
- Author
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Thoby E, Veras J, Nallapati S, Jimenez ME, and Bhise V
- Subjects
- Humans, Adolescent, Female, Male, Young Adult, Adult, Adaptation, Psychological, Interviews as Topic, Quality of Life, Multiple Sclerosis psychology, Multiple Sclerosis therapy, Qualitative Research, Transition to Adult Care
- Abstract
Aim: We sought to explore the experiences and perceptions of the quality of life of adolescents with pediatric-onset multiple sclerosis and assess their readiness for academic, employment and/or health care-related transitions., Background: Adolescents with pediatric-onset multiple sclerosis face unique challenges in managing a chronic illness while navigating future scholastic, social and occupational goals. We conducted a qualitative study with in-depth, semi-structured interviews from July 2017 to March 2019. Adolescents with pediatric-onset multiple sclerosis were recruited from a pediatric neurology subspeciality practice until reaching data saturation. A total of 17 interviews were completed via telephone with participants ages 15 through 26., Results: Through content analysis of the interviews, we identified five major themes: (1) receiving a new diagnosis; (2) adapting to life with pediatric-onset multiple sclerosis; (3) evaluating education/career transition preparedness; (4) adjusting within family life and establishing support systems; and (5) assessing current medical services and preparedness for adult medical care., Conclusions: Autonomy in health care management, adequate control of physical symptoms and sufficient family support impacted perceptions of quality of life. Implementing a dedicated transition visit, including the parent(s) of those with pediatric-onset multiple sclerosis, early in adolescence may provide an avenue for appropriate anticipatory guidance regarding available services, independent medical management and continuity of care., (© 2024 The Author(s). Child: Care, Health and Development published by John Wiley & Sons Ltd.)
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- 2024
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- View/download PDF
50. Mesenchymal stem cells and their derived exosomes in multiple sclerosis disease: from paper to practice.
- Author
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Hamidi SH, Etebar N, Rahimzadegan M, Zali A, Roodsari SR, and Niknazar S
- Subjects
- Humans, Mesenchymal Stem Cell Transplantation, Animals, Cell Communication, Mesenchymal Stem Cells metabolism, Exosomes metabolism, Multiple Sclerosis therapy, Multiple Sclerosis pathology, Multiple Sclerosis metabolism
- Abstract
Multiple sclerosis (MS) is a chronic neurodegenerative, inflammatory, and demyelinating disease of the central nervous system (CNS). Current medicines are not sufficient to control the inflammation and progressive damage to the CNS that is known in MS. These drawbacks highlight the need for novel treatment options. Cell therapy can now be used to treat complex diseases when conventional therapies are ineffective. Mesenchymal stem cells (MSCs) are a diverse group of multipotential non-hematopoietic stromal cells which have immunomodulatory, neurogenesis, and remyelinating capacity. Their advantageous effects mainly rely on paracrine, cell-cell communication and differentiation properties which introduced them as excellent candidates for MS therapy. Exosomes, as one of the MSCs secretomes, have unique properties that make them highly promising candidates for innovative approach in regenerative medicine. This review discusses the therapeutic potential of MSCs and their derived exosomes as a novel treatment for MS, highlighting the differences between these two approaches., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
- Published
- 2024
- Full Text
- View/download PDF
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