Alcalá-Vicente C, Tortosa-Carreres J, Cubas-Núñez L
… +10 more, Quintanilla-Bordás C, Carratalà-Boscà S, Castillo-Villalba J, Verdini L, García-Lluch G, Forés-Toribio L, Gorriz-Romero D, Martínez-Gimeno A, Casanova B, Pérez-Miralles FC
Mult Scler Relat Disord
· 2026 May · PMID 42241787
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BACKGROUND: Multiple sclerosis (MS) exhibits a two-stage disability progression model in which early inflammatory activity influences the timing of moderate disability (EDSS 3.0), whereas subsequent progression is largel...BACKGROUND: Multiple sclerosis (MS) exhibits a two-stage disability progression model in which early inflammatory activity influences the timing of moderate disability (EDSS 3.0), whereas subsequent progression is largely relapse-independent. It remains unclear whether this paradigm persists in the era of high-efficacy disease-modifying therapies (DMTs). OBJECTIVES: To assess whether attainment of sustained EDSS 3.0 via relapse-associated worsening (RAW) or progression independent of relapse activity (PIRA) influences subsequent disability accumulation and to evaluate the impact of DMTs on long-term outcomes. METHODS: We conducted a prospective analysis of 269 relapsing-remitting MS patients followed from disease onset to sustained EDSS 3.0 (≥12 months) and followed for a mean 20.8 years from disease onset. Disability progression to EDSS 3.0 was categorized as RAW or PIRA. PIRMA additionally required absence of MRI inflammatory activity. Kaplan-Meier survival and Cox regression analyses were performed for progression to EDSS 4.0, 6.0, and secondary progressive MS (SPMS), adjusting for age, sex, time from disease onset to treatment initiation and DMT exposure. RESULTS: Of 269 patients, 159 (59%) reached EDSS 3.0 via PIRA and 110 (41%) via RAW. RAW patients attained EDSS 3.0 earlier (median 8.0 vs. 11.0 years) and at younger age (41.1 vs. 46.7 years) than PIRA patients, but time of progression from EDSS 3.0 to 6.0 was comparable. Conversion to SPMS occurred more frequently in the PIRA group (64.7% vs. 35.5%). Multivariable models identified older age and male sex as independent predictors of faster progression. Initial DMT class was not significantly associated with long-term outcomes. CONCLUSIONS: In contemporary treated MS, RAW accelerates early disability accumulation, whereas post-EDSS 3.0 progression converges between RAW and PIRA, supporting a persistent two-stage model of disease evolution. Early intervention to prevent relapse-associated disability and recognition of silent PIRA are critical to preserving long-term neurological function.
Turolla L, Moro M, Boffa G
… +4 more, Odone F, Inglese M, Brayda LG, Casadio M
Mult Scler Relat Disord
· 2026 Jun · PMID 42241786
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Multiple Sclerosis is a neurodegenerative disease frequently associated with gait impairments that can emerge early and progressively worsen, substantially affecting mobility and independence. The Expanded Disability Sta...Multiple Sclerosis is a neurodegenerative disease frequently associated with gait impairments that can emerge early and progressively worsen, substantially affecting mobility and independence. The Expanded Disability Status Scale (EDSS) is widely used to quantify overall disability in people with multiple sclerosis. However, gait alterations may present as specific spatiotemporal and kinematic changes that are not explicitly described by the EDSS scoring criteria. In this context, quantitative gait analysis can provide complementary information on motor function. This study investigates the feasibility of a markerless, single-camera two-dimensional video-based approach to extract quantitative gait parameters in people with multiple sclerosis and to examine whether these measures scale with overall disability level as indexed by scores on the Expanded Disability Status Scale. Twenty people with multiple sclerosis were recorded while walking at a comfortable pace using a standard video camera. Spatiotemporal parameters and lower-limb elevation angles (thigh, shank, and foot) were extracted using the position of the keypoints obtained with a pose estimation algorithm. Associations between these measures and disability scores were assessed. Results showed a significant reduction in normalized stride length and stride time with increasing disability level. In addition, the range of motion of shank and foot elevation angles exhibited strong associations with disability scores. These findings suggest that the range of motion of lower-limb elevation angles, particularly at distal segments, might provide sensitive indicators of disability-related gait impairment. The proposed two-dimensional video-based method offers a low-cost, non-invasive, and unconstrained tool for objective gait assessment in people with multiple sclerosis.
Sandi D, Nyári A, Biernacki T
… +9 more, Kokas Z, Szamosi S, Fricska-Nagy Z, Kincses ZT, Füvesi J, Rózsa C, Vécsei L, Klivényi P, Bencsik K
Mult Scler Relat Disord
· 2026 May · PMID 42241785
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INTRODUCTION: Cognitive impairment (CI) is a significant burden for patients with multiple sclerosis (MS). However crucial its assessment is, longitudinal measurement of cognitive performance is susceptible to learning e...INTRODUCTION: Cognitive impairment (CI) is a significant burden for patients with multiple sclerosis (MS). However crucial its assessment is, longitudinal measurement of cognitive performance is susceptible to learning effect, making the results of repeated evaluations difficult to interpret. Reliable change index (RCI) and standardized regression based norms (SRB) are accepted statistical methods to assess the reliability of a difference score between two observations. Thus, our aims were to provide RCIs and SRBs for all three subtests of the Brief International Cognitive Assessment for MS (BICAMS) battery and to measure the prevalence of true cognitive worsening and improvement. METHODS: We retrospectively evaluated the first interim analysis data of the longitudinal follow-up or our BICAMS prevalence study-cohort after 1-year. We analyzed the data of 242 MS patients. RESULTS: We calculated both the RCIs and the SRBs for all three subtests of the BICAMS battery. According to the RCI, 5.4%, 6.9% and 14.6% worsened while 12.3%, 34.3% and 10.6% improved on the SDMT, BVMT-R and CVLT-II respectively. In case of SRB method, 3.8%, 8.3% and 19.7% worsened while 3.8%, 7.6% and 0.0% improved. The κ values revealed a mild-to-moderate agreement (κ=0.391-0.540; p<0.001). In case of the BVMT-R and the CVLT-II assessments the baseline scores influenced this outcome significantly (BVMT-R: OR: 1.068; 90%CI: 1.001-1.138; CVLT-II: OR: 1.096; 90%CI: 1.041-1.153). CONCLUSION: Comparing the methods, RCI seems to be better in cases with already established CI, while SRB, the more complex method, seemingly detects change better in cognitively intact patients.
Rebei Y, Souissi A, Aissa A
… +8 more, Gharbi A, Abida Y, Atrous A, Kacem I, Gargouri A, Mrabet S, Jomli R, Gouider R
Mult Scler Relat Disord
· 2026 May · PMID 42241784
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BACKGROUND: People living with Multiple Sclerosis (MS) face numerous challenges in their daily lives. To cope with these difficulties and maintain an optimal quality of life, several strategies are employed, including se...BACKGROUND: People living with Multiple Sclerosis (MS) face numerous challenges in their daily lives. To cope with these difficulties and maintain an optimal quality of life, several strategies are employed, including self-management. This study aimed to assess self-management among Tunisian people with MS and identify associated factors. METHODS: A descriptive cross-sectional study on people with MS was conducted in the department of Neurology -Razi University Hospital-Tunisia. Self-management was assessed using the Multiple Sclerosis Self-Management Scale-Revised (MSSM-R), with scores ranging from 24 to 120, where higher scores indicate better self-management capabilities. Anxiety and depression were measured by the Hospital Anxiety and Depression Scale (HADS), personality traits were evaluated using the Big Five Inventory with 10 items (BFI-10), and stigma was assessed with the Stigma Scale for Chronic Illness with 8 items (SSCI-8). A multiple linear regression model was used to identify independent associated variables of the total MSSM-R score. RESULTS: The study included 100 MS patients: 72 women and 28 men with a mean age=34.23years ± 10.29. The mean MSSM-R score was 96.62 ± 9.83. Depression (β =-0.867, p = 0.023), anxiety (β= -0.743, p = 0.04), agreeableness(β = 1.385, p = 0.031), neuroticism(β = -0.634, p = 0.042), and second-line treatment(β = 1.295, p = 0.049) were significantly associated with self-management in the multivariate analysis. No significant association was found with stigma (r =-0.129, p = 0.2). CONCLUSION: The level of self-management among Tunisian people with MS was high. The type of disease-modifying therapy may affect self-management abilities, potentially by shaping patients' perception of their illness.Psychological well-being and personality traits represent important targets for interventions aimed at improving MS self-management.
Mult Scler Relat Disord
· 2026 May · PMID 42241783
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Multiple sclerosis (MS) is a chronic neuroinflammatory disorder, and approximately 50% of MS patients develop depression, making it one of the most common comorbidities of the disease. MS-related depression significantly...Multiple sclerosis (MS) is a chronic neuroinflammatory disorder, and approximately 50% of MS patients develop depression, making it one of the most common comorbidities of the disease. MS-related depression significantly reduces quality of life, worsens neurological disability, and increases suicide risk. Despite its high prevalence, the underlying mechanisms remain unclear. While neuroinflammation and neurotransmitter dysregulation have been implicated, recent evidence suggests that ferroptosis, an iron-dependent form of cell death, may contribute to both neuronal death and mood disturbances in MS patients. Ferroptosis is driven by iron accumulation, lipid peroxidation (LPO), and oxidative stress, all of which are elevated in MS lesions. The inflammatory environment in MS may exacerbate ferroptosis-related processes, potentially contributing to demyelination, neuronal dysfunction, and altered neurotransmitter metabolism-factors strongly linked to depressive symptoms. This review examines the potential role of ferroptosis in MS progression and MS-related depressive symptoms, with a particular focus on oxidative damage and inflammatory signaling related to iron metabolism in the central nervous system (CNS). Understanding these mechanisms may inform future therapeutic hypotheses for MS patients suffering from depression.
Knowles L, Mistretta E, Umucu E
… +3 more, Arellano D, Williams M, Lee B
Mult Scler Relat Disord
· 2026 May · PMID 42235088
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Racial/ethnic minorities with multiple sclerosis (MS) may face additional compounding stressors including access to care and cultural values. This study aimed to investigate the indirect role of resilience and psychologi...Racial/ethnic minorities with multiple sclerosis (MS) may face additional compounding stressors including access to care and cultural values. This study aimed to investigate the indirect role of resilience and psychological distress in the relationship between functional limitations and well-being in a sample of 224 racial/ethnic minorities with MS. Serial mediation analysis was conducted to examine the indirect effect of functional limitations on well-being through resilience and psychological distress. Our findings suggested that functional limitations were negatively associated with resilience and well-being, and were positively associated with psychological distress. Resilience was negatively associated with psychological distress and positively associated with well-being. Our serial mediation results provided preliminary support for resilience and psychological distress as partial mediators between the relationship of functional limitations and well-being. These findings may contribute to an understanding of the roles of resilience and psychological health in the relationship between functional limitations and well-being, which may be critical in addressing disparities in MS care and support.
BACKGROUND: Previous studies indicated that psychological distress increases the risk for disability progression in people with multiple sclerosis (PwMS). It remains unclear whether psychological distress is immune-media...BACKGROUND: Previous studies indicated that psychological distress increases the risk for disability progression in people with multiple sclerosis (PwMS). It remains unclear whether psychological distress is immune-mediated, and thus, an expression of MS or independent thereof. METHODS: In our prospective cohort of PwMS receiving HE-DMT, we invited all patients with "no evidence of disease activity" (NEDA) to fill out the PHQ-ADS questionnaire. We stratified patients according to severity of psychological symptoms and assessed clinical courses including serum neurofilament light-chain (NfL) levels. RESULTS: Among 748 patients, 298 were eligible. 197 patients participated in this analysis. 28.4% showed mild and 22.8% showed clinically significant psychological distress. Psychological distress was associated with confirmed disability worsening (CDW; p = 0.040). NfL assessment showed that patients with distress but normal NfL had no significantly increased hazard for disability worsening (HR:2.2(95%:0.5-9.2)). Conversely, patients with distress and elevated NfL had a high hazard for disability worsening (HR:18.2(95%:4.4-76.3)) even surpassing patients with elevated NfL but without distress (HR:4.1(95%:1.2-14.1)). CONCLUSION: Psychological distress was again common among PwMS and we found that distress increased the risk of disability progression in PwMS and was associated with subclinical activity in several patients. Screening for distress appears warranted to identify these patients at risk.
Generalized anxiety disorder (GAD) is prevalent, yet understudied and poorly managed among persons with multiple sclerosis (MS). Aerobic exercise may manage symptoms of GAD by improving cardiorespiratory fitness (CRF) in...Generalized anxiety disorder (GAD) is prevalent, yet understudied and poorly managed among persons with multiple sclerosis (MS). Aerobic exercise may manage symptoms of GAD by improving cardiorespiratory fitness (CRF) in MS. We examined the association among CRF, trait anxiety, GAD symptoms, and physical activity in a sample with MS prescreened for subclinical GAD. CRF was moderately associated with trait anxiety, but not GAD symptoms. Research should further interrogate the associations in larger samples with MS and GAD.
Immune checkpoint inhibitors (ICIs) are increasingly used in the treatment of advanced malignancies and have been associated with a broad spectrum of immune-related adverse events (irAEs). We present the case of a 65-yea...Immune checkpoint inhibitors (ICIs) are increasingly used in the treatment of advanced malignancies and have been associated with a broad spectrum of immune-related adverse events (irAEs). We present the case of a 65-year-old woman who developed a series of neurological complications, including autoimmune encephalitis, myelitis, and optic neuritis, following treatment with nivolumab and ipilimumab for non-small-cell lung cancer. The clinical and radiological findings supported a diagnosis within the seronegative neuromyelitis optica spectrum disorder/myelin oligodendrocyte glycoprotein antibody-associated disease (NMOSD/MOGAD) spectrum. The patient was treated with high-dose corticosteroids followed by intravenous immunoglobulin (IVIG) as first-line therapy and rituximab as maintenance treatment, resulting in sustained clinical and radiological remission over 30 months of follow-up. To our knowledge, this represents one of the few reported cases of a seronegative central nervous system demyelinating disorder associated with ICIs and among the first to demonstrate a favorable response to IVIG in the acute setting. This case highlights the potential for ICIs to trigger or unmask autoimmune demyelinating syndromes, even in antibody-negative patients, and suggests a potential role for IVIG as an alternative to plasma exchange in selected cases.
OBJECTIVE: To investigate the correlation between cerebrospinal fluid (CSF) and serum biochemical markers and baseline Expanded Disability Status Scale (EDSS) scores in patients with acute-onset multiple sclerosis (MS),...OBJECTIVE: To investigate the correlation between cerebrospinal fluid (CSF) and serum biochemical markers and baseline Expanded Disability Status Scale (EDSS) scores in patients with acute-onset multiple sclerosis (MS), and to identify independent predictors of EDSS-assessed baseline disability. METHODS: A retrospective study included 157 patients with acute-onset MS (82 first-episode, 75 relapse) meeting the 2023 McDonald criteria. Baseline EDSS was assessed during acute exacerbation. CSF and serum samples were collected before corticosteroid administration, and MRI activity was evaluated. Associations were analyzed using Spearman correlation and ordinal logistic regression. RESULTS: The median baseline EDSS score was 2.50 (IQR: 1.50-3.75). Spearman analysis revealed that EDSS scores were negatively correlated with serum albumin (S-Alb, ρ=-0.418, P = 0.001), and positively with CSF protein (ρ=0.173, P = 0.031), CSF-ADA (ρ=0.188, P = 0.019) and CSF-IgG (ρ=0.273, P = 0.001); serum magnesium had no statistical correlation with EDSS (P > 0.05). Multivariate ordinal logistic regression confirmed S-Alb (OR=0.802, 95% CI: 0.741-0.867, P < 0.001) as an independent protective factor and CSF-ADA (OR=1.223, 95% CI: 1.027-1.456, P = 0.024) as an independent risk factor for EDSS-assessed disability; other markers had no independent predictive value (all P > 0.05). Notably, first-episode/relapse status and MRI activity had no significant association with EDSS scores. CONCLUSION: S-Alb and CSF-ADA are independent influencing factors for EDSS-assessed baseline disability in acute-onset MS. Elevated S-Alb levels and reduced CSF-ADA activity are associated with lower EDSS scores and milder neurological deficits, serving as exploratory objective biological indicators for baseline disability evaluation and providing evidence for clinical stratified intervention and neuroprotective therapy research.
BACKGROUND: Motor and cognitive impairments in multiple sclerosis are progressive in nature and impair independence and overall quality of life. Although the use of a treadmill improves gait and endurance, there is limit...BACKGROUND: Motor and cognitive impairments in multiple sclerosis are progressive in nature and impair independence and overall quality of life. Although the use of a treadmill improves gait and endurance, there is limited benefit in regard to cognitive motor integration. Virtual reality offers multi-sensory, task-oriented environments that can enhance engagement and combine motor and cognitive rehabilitation. OBJECTIVES: This systematic review assessed the effectiveness of VR-enhanced treadmill training versus conventional treadmill training on gait, endurance, balance, and cognitive-motor performance in individuals with MS. METHODS: The comprehensive database search identified randomized controlled trials and observational studies comparing VR+TT with TT in adults with MS. Study screening, data extraction, and quality assessment were performed independently by two reviewers using Cochrane RoB 2 and Newcastle-Ottawa Scale tools. RESULTS: Six studies met inclusion criteria, three of which were RCTs, and three were observational. VR+TT resulted in larger improvements in gait speed, stride length, and functional mobility compared with TT alone. Improved performance was also seen in the Timed Up and Go, 25-Foot Walk, and 6-Minute Walk Tests. Dual-task walking and cognitive performance, assessed using the Symbol Digit Modalities Test, significantly improved in VR+TT groups. Participants were highly motivated and demonstrated good adherence, with few adverse effects. CONCLUSION: VR-treadmill training was associated with greater improvements in both motor and cognitive performance relative to treadmill training alone in people with multiple sclerosis. Our results indicate that immersive, feedback-driven environments could facilitate the integration of motor-cognitive function yet sufficiently powered, and methodologically rigorous trials are necessary to confirm long-term efficacy and clinical relevance.
BACKGROUND: The risk factors for headaches associated with Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) have not been systematically documented. OBJECTIVES: We aim to describe the risk factors...BACKGROUND: The risk factors for headaches associated with Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) have not been systematically documented. OBJECTIVES: We aim to describe the risk factors for headaches occurring in MOGAD. RESULTS: The prevalence of headaches was 26.3% at onset and 31.4% during the whole course, with headaches more frequently observed during the initial attack (p = 0.002). More patients with headaches experienced cerebral cortical encephalitis (CCE, at onset and all attacks, p < 0.001), elevated MOG-IgG titres (at onset, p = 0.013, all attacks p = 0.038), increased cerebrospinal fluid total protein (TP, all attacks, p = 0.011), more cortical lesion (all attacks, p = 0.046), leptomeningeal enhancement (at onset and all attacks, p = 0.001) and tumefactive demyelination (all attacks, p = 0.025) on MRI. The univariate analysis and multivariable analysis illustrated that the dominant features associated with headaches were CCE event (p = 0.007), leptomeningeal enhancement (p = 0.048), and tumefactive demyelination on MRI (p = 0.013). MOGAD patients often experienced CCE events and leptomeningeal enhancement on MRI simultaneously (p < 0.001). CONCLUSION: CCE, leptomeningeal enhancement and tumefactive demyelination are the dominant factors associated with headache in MOGAD.
BACKGROUND: Cognitively stimulating activities (CSAs) are associated with cognitive reserve in people with multiple sclerosis (pwMS). OBJECTIVE: To investigate the effect of 12 weeks of increased CSA engagement on object...BACKGROUND: Cognitively stimulating activities (CSAs) are associated with cognitive reserve in people with multiple sclerosis (pwMS). OBJECTIVE: To investigate the effect of 12 weeks of increased CSA engagement on objective and subjective cognition. METHODS: Using computer-generated allocation tables, sixty non-depressed pwMS were randomized (1:1), stratified by disease course, to a 12-week CSA intervention or passive control. The main inclusion criteria were age 18-65, an Expanded Disability Status Scale score ≤ 6.5, and cognitive impairment. Co-primary endpoints were mean change scores from baseline to 12-week follow-up on the oral Symbol Digit Modalities Test (SDMT) and the Multiple Sclerosis Neuropsychological Questionnaire (MSNQ). These were assessed using Analysis of Covariance, adjusting for group, baseline score, and education. The trial was registered at Clinicaltrials.org (NCT05691192) RESULTS: There was no significant between-group difference in SDMT change scores (β = 2.35, 95% CI [-1.14, 5.85], p = 0.18). There was a significant difference in MSNQ change scores driven by worsening in the control group (β = -4.38, 95% CI [-7.58, -1.17], p = 0.0084). CONCLUSION: The intervention was not associated with improvements in objective cognition. Although a difference was observed for subjective cognition, this was driven by worsening in the control group.
Psychological resilience has emerged as a robust protective factor in multiple sclerosis (MS), consistently associated with reduced depression, lower fear of relapse, and improved health-related quality of life. However,...Psychological resilience has emerged as a robust protective factor in multiple sclerosis (MS), consistently associated with reduced depression, lower fear of relapse, and improved health-related quality of life. However, resilience in MS has been predominantly conceptualized as an intrapersonal psychological trait, limiting its explanatory scope for cognitive and neurological outcomes. In this theoretical manuscript, we propose reconceptualizing psychological resilience as a dynamic behavioral-psychological system that may function as a behavioral proxy for cognitive reserve. This proposal is grounded in converging evidence indicating that resilience is associated with sustained engagement in behaviors known to support cognitive reserve, including physical activity, social participation, and adaptive health self-management. While direct causal relationships remain to be established, this framework offers an integrative perspective linking psychological adaptation, behavioral engagement, and neuroprotection in MS and related neurodegenerative conditions.
UNLABELLED: Real-world evidence (RWE) plays an increasingly important role in multiple sclerosis (MS) and related disorders, complementing randomized clinical trials by capturing effectiveness, safety, treatment persiste...UNLABELLED: Real-world evidence (RWE) plays an increasingly important role in multiple sclerosis (MS) and related disorders, complementing randomized clinical trials by capturing effectiveness, safety, treatment persistence, and access patterns in routine care. In Latin America (LATAM), fragmented healthcare systems and structural inequities in access to diagnosis, magnetic resonance imaging (MRI), biomarkers, and high-cost therapies underscore the need for regionally applicable real-world data. OBJECTIVES: To provide a practical methodological framework for the design, implementation, and sustainability of clinical registries in LATAM, drawing on regional experience in MS and neuromyelitis optica spectrum disorder (NMOSD). DESIGN/APPROACH: Narrative review integrating methodological principles for registry development with lessons learned from the implementation of multicenter MS registries in LATAM. Key domains analyzed include definition of objectives, core dataset selection, representativeness, bias mitigation, governance, data quality assurance, ethical considerations, and sustainability strategies. RESULTS: Clinical registries, when based on clearly defined objectives and essential minimum variables, enable standardized longitudinal data collection in routine practice. Regional experience highlights recurrent challenges, including selection bias toward high-complexity centers, missing data, operational burden, and governance conflicts. Pragmatic strategies-such as core datasets, progressive center inclusion, predefined authorship rules, and early dissemination of results-improve feasibility and long-term sustainability. Registries also provide actionable evidence on diagnostic timelines, treatment initiation, persistence, and access disparities, supporting clinical, regulatory, and health technology assessment decisions. CONCLUSIONS: Well-designed clinical registries represent a strategic platform for generating high-quality RWE in MS and related disorders in LATAM. By combining methodological rigor with operational pragmatism, registries can quantify healthcare gaps, enhance regional collaboration, and contribute to more equitable and evidence-informed decision-making.
BACKGROUND: Multiple sclerosis (MS) is a prevalent neurodegenerative disorder (NDD) affecting young adults. While responses to interferon-beta (IFN-β) vary significantly among patients, it has remained a cornerstone of M...BACKGROUND: Multiple sclerosis (MS) is a prevalent neurodegenerative disorder (NDD) affecting young adults. While responses to interferon-beta (IFN-β) vary significantly among patients, it has remained a cornerstone of MS treatment for decades. Increasing evidence suggests that microRNAs (miRNAs) play a crucial role in immune modulation and may influence variations in treatment outcomes. Therefore, this systematic review aims to investigate the role of miRNAs in affecting the therapeutic efficacy, response, and mechanisms of IFN-β therapy in patients with MS. METHOD: This systematic review was conducted in accordance with the PRISMA guidelines. A comprehensive search of PubMed, Scopus, Web of Science, and ScienceDirect databases was performed for studies published up to 2025. Studies investigating miRNA expression levels in RRMS patients who were treated/ responded compared to those who were untreated and non-responders were included in this review. A weighted vote-counting synthesis approach was applied to prioritize significantly dysregulated miRNAs based on directional consistency (upregulation/downregulation) and effective sample-size contribution. Subsequently, target prediction performed for miRNAs introduced without targets. Ultimately, miRNA-target network and PPI network constructed and analyzed and pathway enrichment analysis performed. RESULTS: 13 studies were included based on the eligibility criteria, collectively reporting changes in the expression levels of over 184 miRNAs related to IFN-β therapy. Significantly dysregulated miRNAs including miR-29b, miR-504, miR-185-5p, and miR-27a were found based on weighted vote-counting synthesis approach. miR-29b-1-5p, miR-193a-3p, miR-346, miR-27a-5p were hub miRNAs come from the miRNA-target interaction network and 10 hub genes came from the PPI network. The results of pathways enrichment analysis indicated that miRNAs and hub genes mainly involved in immune regulation, interferon signaling, and neuroinflammatory mechanisms. CONCLUSION: These findings could illuminate miRNAs' mediated mechanisms in IFN-β-treated RRMS patients and aid in creating more specialized and effective treatment options for MS patients.
BACKGROUND: Multiple sclerosis (MS) is a chronic disease in which the immune system attacks itself causing demyelination of the central nervous system. It usually results in cognitive impairment. Cognitive impairment (CI...BACKGROUND: Multiple sclerosis (MS) is a chronic disease in which the immune system attacks itself causing demyelination of the central nervous system. It usually results in cognitive impairment. Cognitive impairment (CI) has an impact on hand function as manual dexterity and bimanual coordination. Brain gym is one of multiple physical therapy modalities that used to improve cognitive function through increasing blood flow, increasing synthesis and utilization of neurotransmitters, and increased synthesis and release of brain-derived neurotrophic factor. METHODS: A total of 36 patients were chosen randomly. These patients were diagnosed with mild CI due to relapsing remitting multiple sclerosis (RRMS). The participants included 20 females and 16 males. Divided into two equal groups, the study group (SG) included 18 patients, and the control group (CG) includes 18 patients. CG received conventional physical therapy program in form of upper extremities coordination training & Strength training exercises. SG received educational kinesiology program, in addition to conventional physical therapy program the same as CG. Treatment was conducted 3times per week, for 4 weeks. The study was starting in January 2024 and continuing until May 2025.Complete clinical evaluations were conducted on all individuals by RehaCom screening modules and Purdue pegboard test. RESULTS: in comparing among both groups, the study group showed a significant increase in cognitive functions, manual dexterity and bimanual co-ordination, while control group did not improve in cognitive function but improved in manual dexterity and bimanual co-ordination but less than the study group. CONCLUSION: brain gym is effective in enhancing cognitive functions, manual dexterity and bimanual co-ordination in RRMS patients with mild CI.