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Advances in Multiple Sclerosis: From Pathogenesis to Therapeutics
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Advances in Multiple Sclerosis: From Pathogenesis to Therapeutics

A special issue of Sclerosis (ISSN 2813-3064).

Deadline for manuscript submissions: 1 June 2026 | Viewed by 2090

Special Issue Editors

Dr. Panagiotis Gklinos

E-Mail Website
Guest Editor
1st Neurology Department, Eginition University Hospital, National and Kapodistrian University of Athens, Athens, Greece
Interests: multiple sclerosis; autoimmune disorders; immune-mediated neurologic disorders; migraine; headache; neurology; neuroscience; demyelination
Prof. Dr. Dimos D. Mitsikostas

E-Mail Website
Guest Editor
1st Neurology Department, Eginition University Hospital, National and Kapodistrian University of Athens, Athens, Greece
Interests: headaches; migraine; placebo/nocebo; multiple sclerosis (MS); functional neurological disorders
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Multiple Sclerosis (MS) is a chronic, immune-mediated disease of the central nervous system (CNS), characterized by neuroinflammation, neurodegeneration, and varying degrees of disability. Although remarkable progress in neuroimaging, biomarker discovery, and treatment has been achieved, significant challenges persist, including the lack of effective therapies to address compartmentalized or smouldering inflammation, which appears to drive disability accumulation even from the earliest stages of the disease.

The recent 2024 revision of the McDonald criteria introduces a biologically based definition of the disease and allows for an earlier diagnosis, even from the stage of radiologically isolated syndrome (RIS), through advanced imaging sequences, novel biomarkers, and the inclusion of the optic nerve as a fifth topography. Novel therapies, including Bruton's Tyrosine Kinase Inhibitors (BTKis), chimeric antigen receptor T (CAR-T) cell therapies, and remyelination therapies, are being tested and hold promise for the near future.

This Special Issue, “Advances in Multiple Sclerosis: From Pathogenesis to Therapeutics”, focuses on the rapidly evolving landscape of MS. We invite researchers with contributions exploring all aspects of MS, including novel biomarkers of disease activity and progression, clinical and real-world evaluations of disease-modifying therapies (DMTs), as well as innovative symptomatic and rehabilitative strategies. Special attention will be given to studies addressing smouldering disease mechanisms, including the role of microglia, and to those examining clinical, radiological, and biochemical outcomes for the assessment of CNS compartmentalized inflammation.

Through cutting-edge research, this Special Issue aims to advance both knowledge and practice in MS by bridging pathophysiological, diagnostic, and therapeutic aspects of the disease. Authors are welcome to submit original articles, reports on novel treatment strategies and advances in decision making, clinical outcome studies, comparative studies, narrative reviews, scoping reviews and systematic reviews, and meta-analyses.

You may choose our Joint Special Issue in Medicina.

Dr. Panagiotis Gklinos
Prof. Dr. Dimos D. Mitsikostas
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Sclerosis is an international peer-reviewed open access quarterly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1000 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • multiple sclerosis
  • biomarkers
  • imaging
  • McDonald 2024 criteria
  • disease-modifying therapies
  • smoldering disease
  • progression independent of relapse activity
  • remyelination
  • microglia
  • clinical research

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Further information on MDPI's Special Issue policies can be found here.

Published Papers (2 papers)

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Review

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19 pages, 657 KB  
Review
When Multiple Sclerosis Overlaps with Neuromuscular Disorders: Clinical Associations, Shared Mechanisms, and Diagnostic Challenges
by Christian Messina
Sclerosis 2026, 4(1), 6; https://doi.org/10.3390/sclerosis4010006 - 9 Mar 2026
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Abstract
Multiple sclerosis (MS) is a chronic immune-mediated demyelinating disorder of the central nervous system, traditionally considered distinct from neuromuscular diseases, which primarily affect the peripheral nervous system, neuromuscular junction, or skeletal muscle. Growing clinical and experimental evidence, however, indicates that certain neuromuscular disorders [...] Read more.
Multiple sclerosis (MS) is a chronic immune-mediated demyelinating disorder of the central nervous system, traditionally considered distinct from neuromuscular diseases, which primarily affect the peripheral nervous system, neuromuscular junction, or skeletal muscle. Growing clinical and experimental evidence, however, indicates that certain neuromuscular disorders may coexist with MS or shared overlapping pathophysiological, immunological, and metabolic mechanisms. This narrative review summarizes reported associations between MS and neuromuscular diseases, with particular focus on well-characterized overlaps such as Leber hereditary optic neuropathy (LHON)-associated MS (Harding’s disease), combined central and peripheral demyelination (CCPD), and myasthenia gravis (MG) co-occurring with MS. Additional associations with Charcot–Marie–Tooth disease, mitochondrial disorders with MS-like phenotypes, inherited and autoimmune myopathies, and rare syndromes such as Guillain–Barré syndrome are also discussed. This review highlights proposed mechanisms potentially linking these conditions, including immune dysregulation, T- and B-cell-mediated autoimmunity, antibody-driven demyelination, mitochondrial dysfunction, impaired neuromuscular transmission, and molecular mimicry. Limitations of the current literature are acknowledged, particularly the predominance of case reports for rare associations and the frequent lack of systematic screening for coexisting disorders. By integrating evidence from case series, cohort studies, and mechanistic research, this review provides a comprehensive overview of the biological and clinical intersections between MS and neuromuscular diseases. Enhanced understanding of these overlaps may improve diagnostic accuracy, guide individualized management strategies, and inform future research on shared neuroimmunological and neurodegenerative pathways. Full article
(This article belongs to the Special Issue Advances in Multiple Sclerosis: From Pathogenesis to Therapeutics)
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11 pages, 753 KB  
Systematic Review
Risk Factors for Relapses in Multiple Sclerosis Beyond Disease-Modifying Therapy: An Umbrella Review of Systematic Reviews and Meta-Analyses
by Sara Terrim, Samira Luisa Apostolos-Pereira, Thiago Ivan Vilchez Santillan, Tarso Adoni, Dagoberto Callegaro and Guilherme Diogo Silva
Sclerosis 2025, 3(4), 41; https://doi.org/10.3390/sclerosis3040041 - 10 Dec 2025
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Abstract
Background/Objectives: People with MS continue to experience relapses despite the use of disease-modifying therapies. This has motivated growing interest in the potential of non-pharmacological factors to reduce relapse risk. However, previous studies have been heterogeneous, and current clinical guidelines lack clarity on which [...] Read more.
Background/Objectives: People with MS continue to experience relapses despite the use of disease-modifying therapies. This has motivated growing interest in the potential of non-pharmacological factors to reduce relapse risk. However, previous studies have been heterogeneous, and current clinical guidelines lack clarity on which measures should be incorporated into routine care. We aim to conduct an umbrella review of systematic reviews with meta-analyses to determine the current evidence on non-pharmacological exposures associated with relapse risk in MS. Methods: We searched PubMed, Embase and Cochrane to identify systematic reviews with meta-analyses that evaluated the association between non-pharmacological exposures and relapse risk. We included observational studies that reported on relapses as an outcome. The effect sizes (relative risk [RR] or standardized mean difference [SMD]) and certainty of evidence were assessed using components of the GRADE framework. Results: We screened 3366 articles and identified 11 systematic reviews for inclusion. Protective factors were breastfeeding (RR 0.63, high certainty), pregnancy (SMD −0.52, moderate certainty), menopause (SMD −0.5, low certainty), autumn months (RR 0.97, moderate certainty) and increasing levels of vitamin D (RR 0.9, low certainty). Risk factors were early postpartum period (RR 1.87, moderate certainty) and stress (d = 0.53, moderate certainty). Influenza vaccination (low certainty), COVID-19 infection (low certainty), and vitamin D levels above 50 nmol/L (low certainty) were not statistically associated with relapse risk. Conclusions: Our umbrella review highlights the need for more robust studies to strengthen the certainty of evidence on non-pharmacological exposures and relapse risk in people with MS. Current findings support promoting breastfeeding, careful disease management throughout the pregnancy–postpartum period, and the implementation of stress mitigation strategies. Full article
(This article belongs to the Special Issue Advances in Multiple Sclerosis: From Pathogenesis to Therapeutics)
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