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Open research questions in Multiple Sclerosis Research Studies

262 unresolved questions extracted from the limitations and future-work sections of 1,039 Multiple Sclerosis Research Studies papers in our library. Each links back to the study that raised it.

What the literature leaves open

  • Further study of the 10-protein signature, - Investigation of the underlying mechanisms of the identified biomarkers, - Development of diagnostic tests based on the identified biomarkers

    Prognostic Biomarker Signature of Relapse in Neuromyelitis Optica Spectrum Disorders in the CIRCLES Observational Study · 2026 · DOI

  • The ability to predict and prevent relapses in NMOSD is crucial for improving clinical outcomes. There is a need for biomarkers that can predict relapse in NMOSD.

    Prognostic Biomarker Signature of Relapse in Neuromyelitis Optica Spectrum Disorders in the CIRCLES Observational Study · 2026 · DOI

  • development of composite biomarkers to stratify MS patients and predict progression - mechanistically grounded EBV-directed interventions that can interrupt the autoimmune cascade - investigation of the specific EBV latency programs and B-cell states

    EBV-driven Gate–License–Amplify circuit in multiple sclerosis pathogenesis · 2026 · DOI

  • The gap in current understanding lies in the mechanisms by which EBV influences antigen presentation and survival licensing. The paper identifies a need to understand how LMP1-mediated survival signaling operates spatially across human CNS compartments. The gap also includes understanding which specific EBV latency programs and B-cell states generate the DR15 myelin-peptidome.

    EBV-driven Gate–License–Amplify circuit in multiple sclerosis pathogenesis · 2026 · DOI

  • limited to post-mortem brain samples, - small sample size of 7 blocks of fresh-frozen tissue, - no significant T or B lymphocyte presence signal was detected in any sample

    Stage-Specific Gene Expression Profiles in Multiple Sclerosis Cortical Lesions Identified via Spatial Transcriptomics · 2026 · DOI

  • future studies at both the gene and protein levels, - examining NAWM, - investigating the molecular mechanisms underlying MS lesion progression

    Stage-Specific Gene Expression Profiles in Multiple Sclerosis Cortical Lesions Identified via Spatial Transcriptomics · 2026 · DOI

  • The primary limitation of this study was its small sample size, which may affect the generalizability of the findings. Given the multifactorial nature of fatigue in multiple scle- rosis and the potential interrelationships among factors such as sleep quality, mood, anxiety, and pain, independent asso- ciations could not be determined.

    Fatigue and contributing factors in relapsing-remitting multiple sclerosis: a descriptive study based on the comprehensive fatigue assessment battery for multiple sclerosis (CFAB-MS) · 2026 · DOI

  • Further studies are needed to confirm these findings, - Investigation of the relationship between cardiovascular measures and IPS in larger samples, - Examination of the effects of different exercise workloads on IPS in PwMS

    Cardiovascular–Cognitive Associations During Physiological Challenges in Relapsing-Remitting Multiple Sclerosis · 2026 · DOI

  • The relationship between cardiovascular measures and information processing speed during acute physiologic challenges is unexplored. Prior studies have not examined the association between cardiovascular responses and cognitive performance in people with multiple sclerosis during acute physiologic challenges.

    Cardiovascular–Cognitive Associations During Physiological Challenges in Relapsing-Remitting Multiple Sclerosis · 2026 · DOI

  • No randomization was performed, - The study relied on a convenience sample, - The analysis was limited to a specific population (MS and LCOF patients), - The study did not control for other potential factors that could influence fatigue

    EEG-based frontal excitation/inhibition balance as an objective biomarker for cognitive fatigue across multiple sclerosis and Long COVID · 2026 · DOI

  • Investigating the underlying mechanisms of altered prefrontal E/I balance in cognitive fatigue, - Examining the potential of the aperiodic exponent as a biomarker for other neurological conditions, - Developing targeted interventions to alleviate cognitive fatigue based on the aperiodic exponent, - Exploring the relationship between the aperiodic exponent and other symptoms of MS and LCOF

    EEG-based frontal excitation/inhibition balance as an objective biomarker for cognitive fatigue across multiple sclerosis and Long COVID · 2026 · DOI

  • Investigating the effects of GBCAs on other brain regions - Studying the long-term consequences of GBCA exposure on cognitive function - Examining the potential benefits and risks of using GBCAs in patients with MS

    Gadolinium-based Contrast Agents Trigger Gadolinium Accumulation Within the Hippocampus In Vivo and Mitochondrial Alterations in Organotypic Hippocampal Tissue Cultures Ex Vivo · 2026 · DOI

  • The effects of chronic GBCA exposure on living hippocampal tissue under inflammatory conditions remain insufficiently understood. The impact of inflammation on gadolinium retention and mitochondrial dynamics is not well understood.

    Gadolinium-based Contrast Agents Trigger Gadolinium Accumulation Within the Hippocampus In Vivo and Mitochondrial Alterations in Organotypic Hippocampal Tissue Cultures Ex Vivo · 2026 · DOI

  • Limited high-quality, large-scale, randomized controlled trials for NMOSD. Need for effective treatment options for patients with AQP4-IgG+ NMOSD.

    Obinutuzumab β for aquaporin-4-positive neuromyelitis optica spectrum disorder: a phase 3 randomized controlled trial · 2026 · DOI

  • Investigating the application of digital pathways in MS management and treatment - Developing a modular-integrative framework for the development of digital patient pathways for MS treatment - Exploring the use of AI in digital pathways for MS care

    Building digital patient pathways for the management and treatment of multiple sclerosis · 2024 · DOI

  • Data from experimental models of MS could have a low predictive value, - Most of the described associations show a modest odds ratio and explain close to half of its heritability, - The study lacks a direct association between SNPs and multiple sclerosis

    Oxidative Stress Markers in Multiple Sclerosis · 2024 · DOI

  • Further prospective, multicenter studies with a long-term follow-up period involving a large number of patients with MS and controls are needed, - Research on the association between oxidative stress and MS should be continued, - Studies on the genetic variants of genes related to oxidative stress in patients with MS should be conducted

    Oxidative Stress Markers in Multiple Sclerosis · 2024 · DOI

  • BACKGROUND AND OBJECTIVES: The 2024 McDonald criteria provide new recommendations for multiple sclerosis (MS) diagnosis, but validation of the criteria is lacking.

    Performance of the 2024 McDonald Criteria in Patients Under Evaluation for Suspected Multiple Sclerosis · 2026 · DOI

  • Limitations include the lack of data on central vein sign and kappa free light chains, and missing optic nerve assessment in some patients.

    Performance of the 2024 McDonald Criteria in Patients Under Evaluation for Suspected Multiple Sclerosis · 2026 · DOI

  • BACKGROUND AND OBJECTIVES: Gray matter (GM) damage is a key determinant of clinical disability in multiple sclerosis (MS), but its relevance to very long-term outcomes remains insufficiently characterized.

    Gray Matter Damage and Long-Term Disability, Cognitive Outcome, and Survival in Patients With Multiple Sclerosis · 2026 · DOI

  • While gait and lower limb dysfunction are well studied, foot- and ankle-specific impairments remain underexplored despite their potential impact on mobility, independence, and quality of life.

    Association Between Foot Alterations and Disability in People With Multiple Sclerosis: A Cross-Sectional Study · 2026 · DOI

  • Latent infection with Epstein-Barr virus (EBV) is a strong risk factor for the development of multiple sclerosis (MS), although the underlying mechanisms remain unclear.

    Epstein-Barr virus infection promotes T cell dysregulation in a humanized mouse model of multiple sclerosis · 2025 · DOI

  • Epstein-Barr virus (EBV) is strongly implicated in the pathogenesis of multiple sclerosis (MS), yet its exact role in disease progression remains unclear.

    Epstein–Barr virus and the immune microenvironment in multiple sclerosis: Insights from high-dimensional brain tissue imaging · 2025 · DOI

  • Optic neuritis is the dominant phenotype in this age group with MOGAD and is under-recognized and frequently misdiagnosed.

    Clinical Features and Factors Associated With Outcome in Late Adult-Onset Myelin Oligodendrocyte Glycoprotein Antibody–Associated Disease · 2025 · DOI

  • However, because of the rarity of the disease, little is known concerning how to switch from one treatment to another in case of lack of effectiveness or side effects.

    Severe Relapse After Switching From Eculizumab to Satralizumab in Neuromyelitis Optica Spectrum Disorder · 2025 · DOI

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262 open questions have been extracted from the limitations and future-work passages of 1,039 Multiple Sclerosis Research Studies papers in our library. Each one below links back to the study that raised it, so you can read the original claim in context.

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