Background: Multiple sclerosis (MS) pathology is characterized by acute and chronic inflammation, demyelination, axonal injury, and neurodegeneration. After decades of research into MS-related degeneration, recent efforts have shifted toward recovery and the prevention of further damage. A key area of focus is the remyelination process, where researchers are studying the effects of pharmacotherapy on myelin repair mechanisms. Multiple compounds are being tested for their potential to foster remyelination in different clinical settings through the application of less or more complex techniques to assess their efficacy. Objective: To review current methods and biomarkers to track myelin regeneration and recovery over time in people with MS (PwMS), with potential implications for promyelinating drug testing. Methods: Narrative review, based on a selection of PubMed articles discussing techniques to measure in vivo myelin repair and functional recovery in PwMS. Results: Non-invasive tools, such as structural Magnetic Resonance Imaging (MRI) and Positron Emission Tomography (PET), are being implemented to track myelin repair, while other techniques like evoked potentials, functional MRI, and digital markers allow the assessment of functional recovery. These methods, alone or in combination, have been employed to obtain precise biomarkers of remyelination and recovery in various clinical trials on MS. Conclusions: Combining different techniques to identify myelin restoration in MS could yield novel biomarkers, enhancing the accuracy of clinical trial outcomes for remyelinating therapies in PwMS.

• Klíčová slova
• biomarkers, multiple sclerosis, recovery, remyelination,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

INTRODUCTION: Upper limb (UL) impairment is common in people with multiple sclerosis (pwMS), and functional recovery of the UL is a key rehabilitation goal. Technology-based approaches, like virtual reality (VR), are increasingly promising. While most VR environments are task-oriented, our clinical approach integrates neuroproprioceptive 'facilitation and inhibition' (NFI) principles. To advance this, we developed immersive VR software based on NFI principles targeting UL function and sit-to-stand ability. This study aims to evaluate the effectiveness of this VR therapy compared with conventional NFI-based physical therapy in pwMS. Our study uniquely applies advanced imaging techniques, along with biological molecular assessments, to explore adaptive processes induced by VR rehabilitation. METHODS AND ANALYSIS: This double-arm, randomised, assessor-blinded, controlled trial runs over 2 months (1 hour, 2 times per week). PwMS with mild to severe disability will receive either VR therapy or real-world physical therapy. Primary outcomes include the nine-hole peg test, box and block test, handgrip strength, tremor and five times sit-to-stand test. Secondary measures include the Multiple Sclerosis Impact Scale, the 5-level EQ-5D questionnaire and kinematic analysis. Adaptive processes will be monitored using imaging techniques (functional MRI and tractography), molecular genetic methods (long non-coding RNAs) and immune system markers (leukocytes, dendritic cells). The International Classification of Functioning, Disability and Health brief set for MS will map the bio-psycho-social context of participants. ETHICS AND DISSEMINATION: This project and its amendments were approved by the Ethics Committee of the Institute for Clinical and Experimental Medicine and Thomayer Hospital (1983/21+4772/21 (G-21-02) and the Ethics Committee of Kralovske Vinohrady University Hospital (EK-VP/38/0/2021) in Prague, Czechia (with single enrolment). The findings of this project will be disseminated through scientific publications, conferences, professional networks, public engagement, educational materials and stakeholder briefings to ensure a broad impact across clinical, academic and public domains. TRIAL REGISTRATION NUMBER: clinicaltrials.gov (NCT04807738).

• Klíčová slova
• Functional Magnetic Resonance Imaging, IMMUNOLOGY, Multiple sclerosis, Neuroradiology, REHABILITATION MEDICINE, Virtual Reality,
• MeSH
• dospělí MeSH
• dvojitá slepá metoda MeSH
• horní končetina * patofyziologie   MeSH
• kvalita života * MeSH
• lidé MeSH
• magnetická rezonanční tomografie * metody   MeSH
• postura těla MeSH
• randomizované kontrolované studie jako téma MeSH
• roztroušená skleróza * diagnostické zobrazování   MeSH
• síla ruky MeSH
• techniky fyzikální terapie * MeSH
• terapie pomocí virtuální reality metody   MeSH
• virtuální realita MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• protokol klinické studie MeSH

BACKGROUND AND PURPOSE: Cognitive impairment (CI) in multiple sclerosis (MS) is associated with bidirectional changes in resting-state centrality measures. However, practicable functional magnetic resonance imaging (fMRI) biomarkers of CI are still lacking. The aim of this study was to assess the graph-theory-based degree rank order disruption index (kD) and its association with cognitive processing speed as a marker of CI in patients with MS (PwMS) in a secondary cross-sectional fMRI analysis. METHODS: Differentiation between PwMS and healthy controls (HCs) using kD and its correlation with CI (Symbol Digit Modalities Test) was compared to established imaging biomarkers (regional degree, volumetry, diffusion-weighted imaging, lesion mapping). Additional associations were assessed for fatigue (Fatigue Scale for Motor and Cognitive Functions), gait and global disability. RESULTS: Analysis in 56 PwMS and 58 HCs (35/27 women, median age 45.1/40.5 years) showed lower kD in PwMS than in HCs (median -0.30/-0.06, interquartile range 0.55/0.54; p = 0.009, Mann-Whitney U test), yielding acceptable yet non-superior differentiation (area under curve 0.64). kD and degree in medial prefrontal cortex (MPFC) correlated with CI (kD/MPFC Spearman's ρ = 0.32/-0.45, p = 0.019/0.001, n = 55). kD also explained fatigue (ρ = -0.34, p = 0.010, n = 56) but neither gait nor disability. CONCLUSIONS: kD is a potential biomarker of CI and fatigue warranting further validation.

• Klíčová slova
• biomarkers, cognitive processing speed, fMRI, fatigue, multiple sclerosis,
• MeSH
• dospělí MeSH
• kognitivní dysfunkce etiologie   patofyziologie   diagnostické zobrazování   MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční tomografie * MeSH
• průřezové studie MeSH
• roztroušená skleróza * komplikace   diagnostické zobrazování   patofyziologie   MeSH
• rychlost zpracování MeSH
• únava * patofyziologie   etiologie   diagnostické zobrazování   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH