Search Results (3,871)

Introduction: Multiple sclerosis (MS) is a chronic, inflammatory, demyelinating disease of the central nervous system with a highly heterogeneous clinical course. Early identification of patients at risk of aggressive disease progression is crucial for optimizing therapeutic strategies, including eligibility for highly effective treatments. Objective: The aim of this review was to synthesize current data on prognostic factors in multiple sclerosis, with particular emphasis on their significance in the early stages of the disease and potential clinical implications. Methods: A narrative systematic review of the literature was conducted, including observational studies, cohort studies, meta-analyses, and systematic reviews on the natural course of MS, prognostic factors, and clinical, neuroimaging, and laboratory biomarkers. We comprehensively reviewed PubMed and Scopus databases, focusing on English-language publications. Study selection prioritized longitudinal studies and meta-analyses with clear outcome definitions and sufficient follow-up. Formal quality scoring was not applied due to the narrative design of the review. Results: Key adverse prognostic factors include older age at onset, polysymptomatic onset, high relapse activity in the first years, incomplete remission after relapses, and the primary progressive form. Magnetic resonance imaging features, including the number and location of T2 lesions, contrast activity, the presence of spinal cord lesions, PRLs and SELs, and severe brain atrophy, also have significant predictive value. Increasing importance is being attached to laboratory biomarkers, such as oligoclonal bands, light neurofilaments, free kappa light chains, and GFAP. Conclusions: An integrated assessment of clinical, neuroimaging, and laboratory factors enables more effective risk stratification in patients with newly diagnosed MS. Early identification of an unfavorable prognostic profile may provide a basis for individualizing treatment and considering the use of highly effective therapies early in the course of the disease. Full article

Cognitive decline represents one of the most common clinical manifestations of neurodegenerative diseases (NDs), substantially affecting the quality of life of both patients and their families. Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis are major NDs characterized by a progressive degeneration of the central nervous system, with functional impairments extending beyond motor symptoms to multiple cognitive domains, including memory, attention, language, and executive functions. Increasing evidence highlights misfolded protein accumulation as a key driver of neuronal dysfunction and cognitive deterioration. This narrative review examines the major cognitive deficits associated with these disorders, focusing on the underlying molecular mechanisms, particularly protein aggregation, as well as clinical manifestations and their effects on daily life. Furthermore, current diagnostic tools and emerging therapeutic options for mitigating cognitive decline will be further discussed. Full article

Multiple Sclerosis (MS) is a chronic, autoimmune neurological disease resulting from the interplay between genetic susceptibility and environmental factors. In recent decades, the rising incidence of MS, particularly pediatric-onset forms, has paralleled the global obesity pandemic. This article explores the causal link between pediatric obesity, systemic inflammation, and neuroinflammation, with a specific focus on the microbiota–gut–liver–brain axis. We analyze how nutritional habits can play a pivotal role by inducing dysbiosis, with alteration in microbiota-driven metabolites, and leaky gut related abnormalities—which may trigger blood–brain barrier (BBB) disruption and microglial activation—or by acting as a protective factor, such as through the Mediterranean Diet (MD). Furthermore, we evaluate the emerging therapeutic perspectives offered by Glucagon-Like Peptide-1 (GLP-1) agonists, which may offer dual benefits in weight management and immune modulation. Full article

Myelination is essential for rapid axonal conduction and neuronal integrity, and its loss in demyelinating diseases such as multiple sclerosis (MS) leads to progressive neurological impairment. Despite advances in immunomodulatory therapies, effective strategies that promote remyelination remain limited. Here, we identify Morusin, a prenylated flavonoid natural compound, as a potent enhancer of oligodendrocyte (OL) differentiation and myelination-associated outcomes. Using a fluorescence-based screen of diverse flavonoids in primary rat oligodendrocyte progenitor cells (OPCs), it was found that Morusin markedly increased myelin basic protein (MBP) expression. To enable cross-species validation, we established a SOX10-inducible human OPC differentiation system, which shortened differentiation time and allowed functional screening in human cells. In this platform, Morusin enhanced OL maturation and induced a transcriptional profile enriched for myelination- and axon ensheathment-related genes, including MBP, PLP1, MAG, and SIRT2. Furthermore, in myelin oligodendrocyte glycoprotein (MOG)₃₅–₅₅-induced experimental autoimmune encephalomyelitis (EAE) mice, Morusin improved myelination-associated histological features and functional recovery, comparable to the benchmark compound Benztropine. Collectively, these findings identify Morusin as a promising natural compound with pro-myelinating activity across multiple experimental systems and highlight the potential of rationally guided natural compound screening for regenerative therapy in demyelinating diseases. Full article

Background/Objectives: Multiple sclerosis (MS) significantly impairs quality of life (QoL) beyond physical disability, affecting psychosocial well-being. Although nurses play a central role in holistic, person-centered care, region-specific evidence from Western Greece remains limited. This study aimed to evaluate QoL and its biopsychosocial determinants among adults with MS in Western Greece and synthesize evidence on modifiable factors to guide nursing interventions. Methods: A cross-sectional study was conducted among 128 adults with MS (82% response rate from a pool of 156). QoL was measured with the MSQOL-54, depression with the Beck Depression Inventory-II, and social support with the Multidimensional Scale of Perceived Social Support. Data were analyzed using descriptive statistics, correlations, and multiple regression. Results: Participants reported moderate QoL impairment (Physical Composite Score = 53.6; Mental Composite Score = 57.4). Unemployment (52% of sample) was significantly associated with poorer physical QoL (p < 0.001). Fatigue, pain, and depressive symptoms showed strong negative correlations with QoL (p < 0.001). Higher perceived social support was a significant predictor of better mental health (β = 0.42, p < 0.01). The systematic review confirmed these predictors and reinforced social support as a key protective factor. Conclusions: Nurses should prioritize psychosocial aspects of MS care. Routine assessment and strengthening of social support networks, along with addressing employment barriers, are essential. Integrating targeted psychosocial strategies into standard nursing practice can effectively improve holistic well-being and mitigate QoL deterioration in individuals with MS. Full article

One of the key pathological features of Diabetic Kidney Disease (DKD) progression is the accumulation of extracellular matrix (ECM) proteins in kidneys, leading to thickening of the glomerular and tubular basement membranes, subsequently resulting in mesangial expansion, sclerosis, and tubulointerstitial fibrosis. Given the high prevalence of DKD among both T2DM and T1DM patients, as well as the complexity of its underlying molecular mechanisms, this study provides a comparative analysis of published urinary proteomics datasets in DKD (n = 4). By integrating these data with published tissue proteomics (n = 2) and published transcriptomics datasets (n = 5), the study further aims to link urinary findings to tissue pathophysiology. Through integrative proteomic and transcriptomic analysis, DKD was associated with distinct alterations in the urinary proteome, particularly involving proteins related to ECM turnover. Using multiple validation datasets, several upregulated proteins with potential biological significance were identified, including annexins, collagens, cathepsins, and glycoproteins. Overall, our findings underscore the critical role of ECM remodeling in DKD progression and further validation could open new avenues for biomarker development and targeted therapy in early stages of DKD. Full article

Background and Objectives: Employment is a major determinant of quality of life in people with multiple sclerosis (pwMS). This multicenter cross-sectional study aimed to identify which commonly studied demographic, disease-related, clinical, cognitive, and psychological variables, alongside the presence of lower urinary tract symptoms (LUTS), predict employment status in pwMS. Materials and Methods: Seventy-eight pwMS were classified as either full-time employed (n = 41) or non-employed (n = 37). Participants underwent clinical and neuropsychological assessment including disability status (Expanded Disability Status Scale; EDSS), fatigue (Modified Fatigue Impact Scale; MFIS), information processing speed (Symbol Digit Modalities Test; SDMT), depressive symptoms (Hospital Anxiety and Depression Scale-Depression; HADS-D), and LUTS status (presence/absence), alongside demographic and disease-related variables (sex, age, education level, relationship status, and disease duration). Results: Hierarchical binary logistic regression indicated that higher information processing speed was associated with higher odds of employment (OR = 1.11, p = 0.008), whereas the presence of LUTS was associated with lower odds of employment (OR = 0.13, p = 0.026). Disability severity, fatigue, depressive symptoms, demographic characteristics, and disease duration did not contribute in the final model (p > 0.05). Conclusions: Information processing speed and urinary dysfunction were associated with employment status in pwMS. Within the present sample, the multivariable model including these variables showed good discrimination between employed and non-employed participants. The findings should be interpreted as exploratory, and they require further confirmation in independent cohorts before any potential application is considered. Full article

Background: Bulbar dysfunction is a major complication of amyotrophic lateral sclerosis (ALS). This study aimed to develop and validate a simple, smartphone-based task for the objective assessment of tongue movements and to examine their association with clinical variables. Methods: 37 ALS patients and 20 age- and sex-matched controls performed a tongue lateralization task, recorded with a smartphone. A deep-learning U-Net++-based model was used for segmentation and feature extraction. The frequency and maximum amplitude of tongue movements were quantified. Clinical measures included the ALS Functional Rating Scale-revised (ALSFRS-r) bulbar sub-scores, tongue fasciculations, jaw jerk, and tongue “spasticity”. Between-group differences and associations between tongue metrics and clinical features were assessed. Results: The U-Net++-based model achieved robust segmentation performance. Patients showed lower tongue movement frequency than controls (0.14 vs. 0.40, t = −9.58, p < 0.001). Normalized frequency was associated with dysarthria (t = −3.13, p = 0.003) but not dysphagia (t = −1.05, p = 0.30). Normalized frequency (t = 2.77, p = 0.009) and tongue “spasticity” (t = −2.57, p = 0.015) were both associated with speech performance in a multiple-regression model (R = 0.51, adjusted R² = 0.43). Conclusions: Our method provides an objective, minimally invasive measure of bulbar function in ALS, which correlates with clinical ratings and may detect subtle impairments not captured by standard assessments. This approach offers a promising tool for remote monitoring and may support more effective disease management. Full article

The Background: monoclonal antibody therapies represent high-efficacy treatment options for relapsing forms of multiple sclerosis (MS). However, the absence of direct head-to-head randomized trials and the use of heterogeneous comparators across pivotal studies complicate comparative effectiveness assessments. While network meta-analysis (NMA) offers a framework to integrate evidence, the fragmented structure of the available evidence base precludes a conventional NMA with global indirect comparisons and treatment ranking. Methods: A systematic review with qualitative assessment of treatment effects of randomized controlled trials evaluating monoclonal antibody therapies in relapsing forms of multiple sclerosis was conducted. Annualized relapse rate (ARR) was analyzed as the primary outcome, and six-month confirmed disability progression (CDP) as the key secondary outcome. Network geometry and connectivity were explicitly assessed for each outcome prior to quantitative synthesis. Analyses were restricted to comparator-defined connected components of the evidence base, and indirect comparisons across disconnected components were not performed. Sensitivity analyses, including descriptive analyses in progressive multiple sclerosis, were conducted where appropriate. Results: nine randomized controlled trials involving 6762 patients were included. For ARR, the evidence network was fragmented into three disconnected components defined by placebo-, interferon beta-1a-, and teriflunomide-controlled trials. Within connected sub-networks, monoclonal antibody therapies consistently demonstrated substantial reductions in ARR relative to their respective comparators, with overlapping confidence intervals suggesting broadly comparable relapse suppression among high-efficacy agents. For CDP, network connectivity was more limited, and treatment effects were more heterogeneous. Significant reductions in disability progression were observed for some agents within comparator-specific networks, while uncertainty remained for others. Due to network disconnection, no global treatment ranking was performed. Conclusions: this study provides a transparent synthesis of randomized evidence on monoclonal antibody therapies in relapsing MS. By explicitly accounting for network connectivity and comparator heterogeneity, the analysis avoids unsupported indirect comparisons and global treatment hierarchies. The findings support robust relapse suppression across monoclonal antibody therapies within comparable trial frameworks, while highlighting heterogeneity in disability outcomes. These results illustrate the importance of contextual interpretation in comparative effectiveness research in MS. Full article

Dysregulation of iron and copper homeostasis is a pivotal driver of regulated cell death through two distinct yet interconnected modalities: ferroptosis and cuproptosis. This comprehensive review evaluates the therapeutic modulation of these metal-driven pathways within a dual paradigm: their deployment as a cytotoxic weapon in oncology and their inhibition for neuroprotection. We synthesize evidence ranging from small-molecule synergy to advanced nanomedicine, examining how the interplay between iron and copper governs cellular fate in resistant malignancies and neurodegenerative diseases such as Parkinson’s disease and Multiple Sclerosis. In oncology, bimetallic nanoplatforms and CRISPR-Cas9 nano-ionophores exploit “iron addiction” and metabolic vulnerabilities to induce fatal lipid peroxidation and FDX1-mediated proteotoxic stress, often by circumventing efflux transporters like ATP7A/B. Conversely, neuroprotective strategies focus on site-specific chelation, utilizing brain-penetrant molecules like SK4 (targeting the LAT1 transporter) and radical trapping antioxidants like Cu^II(atsm). Importantly, we elucidate the “iron trap” mechanism, where copper deficiency inactivates multicopper ferroxidases—including ceruloplasmin and hephaestin—thereby triggering iron-dependent ferroptosis. Our analysis reveals a self-amplifying cycle of oxidative damage driven by metal-induced ATP depletion and glutathione exhaustion. By delineating the molecular machinery of iron and copper metabolism, this article provides a roadmap for leveraging regulated cell death to overcome apoptosis resistance in cancer and preserve neural integrity in chronic degeneration. Full article

This study investigated the expression and subcellular localization of chitinase-3-like protein 1 (CHI3L1) in neutrophils and plasma from untreated and dimethyl fumarate (DMF)-treated multiple sclerosis (MS) patients, and healthy controls. Intracellular CHI3L1 expression was assessed in CD66b+ neutrophils and CD16+ cells using flow cytometry. Subcellular localization was analyzed by confocal microscopy using markers for various neutrophil granules, while ELISA measured plasma CHI3L1 and lactoferrin levels. We found that both intracellular CHI3L1 levels (expressed as mean fluorescence intensity, MFI) and the proportion of CD66b+ cells were significantly increased in MS patients compared to healthy controls. CHI3L1 was found to colocalize with CD66b+ specific granules. While plasma CHI3L1 levels in untreated MS patients remained comparable to those of healthy controls, a significant increase in both intracellular and plasma CHI3L1 was observed in DMF-treated MS patients. The lack of correlation between plasma lactoferrin and CHI3L1 might suggest selective release mechanisms or differential synthesis of these proteins, despite their common storage in specific granules. These findings highlight the role of neutrophils as a peripheral source of CHI3L1 and suggest a complex association between neutrophil-derived CHI3L1 and the differences observed in DMF-treated MS patients. Full article

Multiple sclerosis (MS) is characterized by progressive mitochondrial dysfunction affecting complexes I, III, and IV of the electron transport chain, contributing to axonal energy failure and neurodegeneration. This review examines the potential of combining β-hydroxybutyrate (βHB), epigallocatechin-3-gallate (EGCG), and ellagic acid (EA) as a multi-target therapeutic strategy to restore mitochondrial function in patients with MS. Experimental and clinical studies demonstrate that each compound exerts complementary mechanisms. Ketone bodies provide an alternative energy substrate and restore complex I activity via sirtuin-dependent pathways. EGCG acts predominantly at the peripheral level by reducing systemic inflammation and oxidative stress. EA-derived urolithins effectively cross the blood–brain barrier to directly enhance mitochondrial biogenesis and respiratory chain function in the central nervous system. Clinical trials have reported improvements in fatigue, cognition, mood, and muscle function following supplementation with these compounds. The convergence of their actions on energy restoration, reactive oxygen species reduction, and epigenetic modulation of protective pathways suggests their synergistic potential. Optimized delivery strategies, including exogenous ketone salts, liposomal EGCG, and microencapsulated EA, may overcome bioavailability limitations and interindividual variability in the gut microbiota metabolism. Full article

Background/Objectives: Walking impairment and fatigue are common in multiple sclerosis (MS) and contribute to reduced physical function and quality of life (QoL). This study evaluated the feasibility, safety, and pre–post changes associated with a 12-week treadmill walking training (TWT) programme on walking performance, physical function, fatigue, and QoL in people with MS. Methods: Single-arm pilot study with pre–post assessments (T1–T2). Eleven adults with MS (Expanded Disability Status Scale [EDSS] ≤ 6) completed supervised TWT for 12 weeks (two 25 min sessions/week) at the Complejo Asistencial Universitario de Soria (Spain). Outcomes included SF-36, Timed Up and Go (TUG), 4 m gait speed, Short Physical Performance Battery (SPPB), and Modified Fatigue Impact Scale (MFIS). Within-participant changes were analysed using paired t-tests or Wilcoxon signed-rank tests as appropriate; effect sizes were reported as appropriate for the statistical test. Results: SF-36 total score did not change significantly (p = 0.160), while general health (p = 0.039) and vitality (p = 0.043) improved. Walking performance improved (TUG, p = 0.007; 4 m gait speed, p < 0.001), and physical function increased (SPPB, p = 0.003). Fatigue impact decreased (MFIS total, p = 0.015; physical, p = 0.007; psychosocial, p = 0.026), whereas the cognitive subscale did not change significantly (p = 0.094). Adherence was 91.7%, and no adverse events were reported. Conclusions: In this pilot sample, a 12-week TWT programme was feasible and safe and was associated with improvements in walking performance, physical function, and fatigue, with QoL changes limited to specific SF-36 domains. These findings support proceeding to a randomised controlled trial to establish efficacy. These findings should be interpreted as preliminary and exploratory, given the single-arm pre–post study design. Full article

Background/Objectives: Pediatric-onset multiple sclerosis (POMS), defined as onset before age 18, is increasingly recognized as a distinct entity, often associated with a more burdensome disease course and earlier disability milestones than adult-onset MS. Although comorbidities may significantly affect disease progression and outcomes, their prevalence, incidence, risk, and characteristics in POMS remain poorly understood. To date, no systematic review has comprehensively evaluated comorbidities in POMS. The primary aim is to systematically identify and synthesize available evidence on the prevalence, incidence, risk, and characteristics of these comorbidities in POMS populations, as well as any reported effects on disease course, treatment outcomes, and overall clinical management. Methods: We will conduct a systematic review and meta-analysis following a hierarchical and pragmatic analytical strategy tailored to the expected heterogeneity and limited evidence base in POMS. MEDLINE (via PubMed) and Embase (produced by Elsevier) will be searched without date restrictions, combining controlled vocabulary terms (MeSH/Emtree) and relevant keywords for POMS and 15 predefined comorbidity categories. Study selection, abstract and full-text screening, and data extraction will be performed independently by two reviewers using predefined criteria and standardized forms. The primary quantitative outcome will be the pooled prevalence of comorbidities. Where study design and reporting permit, incidence rates will be assessed as secondary outcomes, and risk estimates (e.g., odds ratios) will be evaluated only in studies with appropriate comparator groups. Meta-analyses will be conducted using random-effects models when pooling is feasible. Heterogeneity will be assessed using the I² statistic and Cochran’s Q test, with sensitivity and subgroup analyses performed only when sufficient data are available. When quantitative synthesis is not appropriate due to limited data or substantial heterogeneity, findings will be summarized descriptively. Publication bias will be evaluated using funnel plots and, where applicable, Egger’s and Begg’s tests. This protocol adheres to PRISMA and PRISMA-P guidelines. Discussion: A systematic quantification of comorbidity prevalence, incidence (where available), and risk, together with POMS-specific characteristics and any reported impact on clinical outcomes, is anticipated to provide a crucial evidence base for guiding screening, refining management strategies, and informing future research directions. Ultimately, these findings may improve clinical outcomes and quality of life for children and adolescents with MS. Full article