Search Results (489)

Multiple sclerosis (MS) is an autoimmune and neurodegenerative disease affecting approximately 1 million people in the United States. Despite extensive research into the mechanisms of disease development, many aspects of the biological changes during MS progression and the varying symptoms among patients remain unclear. In the era of high-throughput sequencing, transcriptome databases are flooded with data. However, bulk RNA sequencing (RNA-seq) data are typically used only for differential gene expression analysis. Alternative splicing, a key process that alters the transcriptome, can also be identified from bulk data. Here, we accessed 11 studies with bulk RNA-seq data of postmortem MS patients’ brain samples via NCBI’s Gene Expression Omnibus (GEO). We extracted additional information from these data by identifying exclusively alternatively spliced genes via replicate multivariate analysis of transcript splicing (rMATS) analysis. Our analyses revealed that changes in RNA splicing mediate distinct biological signals compared to those driven by differential gene expression. Gene ontology and protein do-main analyses of genes exclusively regulated by alternative splicing revealed distinct molecular differences between progressive and relapsing–remitting MS as well as among lesions from different brain regions and between white and gray matter. These findings highlight the critical role of alternative splicing and its associated pathways in MS disease development and progression. Full article

Background/Objectives: Quantitative intravoxel incoherent motion (IVIM) imaging, incorporating both diffusion- and perfusion-derived metrics, offers a promising non-invasive approach for assessing tissue microstructure and clinical disability in multiple sclerosis (MS). This study aimed to investigate the correlation and predictive values of the IVIM apparent diffusion coefficient (ADC), true diffusion coefficient (D), and perfusion-derived pseudo-diffusion coefficient (D*) and perfusion fraction (f) parameters with disability status, measured using the Expanded Disability Status Scale (EDSS), in relapsing–remitting MS patients. Methods: This cross-sectional study retrospectively analyzed MRI data from 197 MS patients. Quantitative IVIM parameters were extracted from scans obtained using a 1.5 T MRI scanner. Clinical data were also obtained, including age, disease duration, number of relapses, disease-modifying therapy (DMT) status, and need for mobility assistance. Bivariate analyses were conducted to compare mean values across subgroups. Pearson correlation was used to examine associations between EDSS score and imaging/clinical variables. Multiple linear regression was applied to identify independent predictors of EDSS score. Results: The bivariate analyses revealed that ADC, D, D*, and EDSS values were higher in patients over 50 years old, those with a longer disease duration, and those who required mobility assistance. f was higher in females and DMT-treated patients, but it had no effect on EDSS score. Patients with longer disease duration and limited mobility had a higher number of MS lesions and relapses. EDSS score exhibited positive Pearson correlations with ADC, D, D*, the number of MS lesions, and the number of relapses (p-value < 0.001). In the multivariate regression analysis, only the number of MS lesions and relapses emerged as independent predictors of EDSS score (p-value < 0.001). Other variables, including ADC, D, D*, f, age, and disease duration, were not independently associated with EDSS score (p-value > 0.05). Conclusions: This study demonstrates the utility of IVIM parameters in detecting microstructural alterations associated with MS impairment. Despite relapse frequency and lesion count being the strongest predictors of EDSS score, IVIM metrics showed meaningful clinical correlations. The findings support combining IVIM biomarkers with clinical data for better disability assessment. Full article

Adipocytokines are involved in the pathogenesis of multiple sclerosis by modulating inflammation, blood–brain barrier function and immune responses, which may affect disease course and treatment outcomes. Our study assessed serum levels of visfatin, adiponectin and resistin in patients with relapsing–remitting multiple sclerosis treated with fingolimod or natalizumab. We examined 49 patients with relapsing–remitting multiple sclerosis and 38 healthy controls. Participants were divided into three groups: patients treated with fingolimod, those treated with natalizumab and the controls. Serum levels of visfatin, adiponectin and resistin were measured. We analyzed correlations with disease duration, treatment duration and body mass index. Adiponectin levels were significantly higher in patients treated with natalizumab compared to those receiving fingolimod and healthy controls (p < 0.05). In the fingolimod group, visfatin levels increased with treatment duration. The mean level was 51.27 pg/mL for treatment shorter than eighteen months and 59.12 pg/mL for longer treatment (p < 0.05). In the same group, resistin levels correlated positively with body mass index (p < 0.05), while visfatin levels showed a negative correlation (p < 0.05). Fingolimod may affect adipocytokine levels, which could support patient monitoring. Increased adiponectin in natalizumab-treated patients suggests its possible role in the therapeutic mechanism of the treatment. Full article

Inflammatory bowel disease (IBD) is a relapsing–remitting condition resulting in chronic inflammation of the gastrointestinal tract. Present methods are either inadequate or not viable for continuous tracking of disease progression in individuals. In this study, we present the development towards an implantable biosensor for detecting interleukin-6 (IL-6), an important cytokine implicated in IBD. The optimised sensor design includes a gold surface functionalised with a known IL-6-specific aptamer, integrating a recognition sequence and an electrochemical redox probe. The IL-6 aptasensor demonstrated a sensitivity of up to 40% and selectivity up to 10% to the IL-6 target in vitro. Sensors were found to degrade over 7 days when exposed to recombinant IL-6, with the degradation rate rapidly increasing when exposed to intestinal mucosa. A feasibility in vivo experiment with a newly designed implantable gut sensor array confirmed rapid degradation over a 5-h implantation period. We achieved up to a 93% reduction in sensor degradation rates, with a polyvinyl alcohol–methyl acrylate hydrogel coating that aimed to reduce nonspecific interactions in complex analytes compared to uncoated sensors. Degradation was linked to desorption of the monolayer leading to breakage of gold thiol bonds. While there are key challenges to be resolved before a stable implantable IBD sensor is realised, this work highlights the potential of aptamer-based biosensors as effective tools for long-term diagnostic monitoring in IBD. Full article

Background/Objectives: Multiple sclerosis (MS) is a chronic neurodegenerative disorder mainly affecting young adults and can greatly impair quality of life (QoL). Among its often overlooked but significant symptoms are bowel dysfunctions (BD), such as constipation and fecal incontinence, which can impact physical, emotional, and social well-being, especially in younger patients. This study aims to investigate the impact of BD on the QoL in young adults diagnosed with relapsing-remitting MS (RRMS) and mild disability. Methods: This retrospective cross-sectional study examined the effect of BD on QoL in 110 young adults with RRMS and mild disability (EDSS ≤ 3.5). Bowel symptoms were assessed using the Wexner Incontinence and Constipation Scales, while QoL was measured with the MSQoL-54 questionnaire. Statistical analyses were performed to examine correlations between BD severity and QoL domains. Results: Our findings showed significant correlations between the severity of intestinal symptoms and different domains of QoL, like physical functioning, emotional well-being, and social functioning. Abdominal pain and liquid fecal incontinence were especially linked to lower mental and physical health scores. Subgroup analyses also indicated gender-specific vulnerabilities, with women showing distinct effects on social and emotional dimensions. Conclusion: BD represents an important burden on bowel dysfunctions for young people with MS, deeply impacting various dimensions of QoL. This underscores an urgent need for an integrated, multidisciplinary care model that tackles physical symptoms but also psychological and social challenges. A holistic clinical strategy is vital to improving the overall well-being of this population. Full article

Inflammatory bowel disease (IBD), a chronic inflammatory disorder with relapsing/remitting characteristics, lacks reliable non-invasive biomarkers for accurate diagnosis and longitudinal monitoring. This study explored salivary exosomal miRNAs as potential biomarkers to address this unmet clinical need. Using discovery (24 IBD patients [11 active, 13 remission] and 6 healthy controls [HCs]) and validation cohorts (102 IBD patients [53 active, 49 remission] and 18 HCs), we analyzed miRNA profiles via reverse transcription quantitative PCR (RT-qPCR). Receiver operating characteristic (ROC) curves evaluated diagnostic performance, with area under the curve (AUC) quantifying discriminatory capacity. Initial screening revealed 23 miRNAs significantly upregulated in IBD salivary exosomes. An 8-miRNA signature distinguished IBD patients from HCs in validation analyses, with five miRNAs (hsa-miR-1246, hsa-miR-142-3p, hsa-miR-16-5p, hsa-miR-301a-3p, and hsa-miR-4516) showing strong correlations with disease activity. The combination of hsa-miR-16-5p and hsa-miR-4516 achieved robust discrimination (AUC = 0.925 for IBD vs. HCs; AUC = 0.82 for active disease vs. remission). A composite model integrating all five miRNAs demonstrated superior performance (AUC = 1.00 for IBD/HC differentiation; AUC = 0.86 for disease activity assessment). These findings reveal dynamic associations between salivary exosomal miRNA signatures and IBD progression, underscoring their utility as non-invasive diagnostic tools. This approach enables serial sampling, enhances patient compliance, and provides actionable insights for personalized disease management, establishing salivary exosomal miRNAs as promising candidates for clinical translation in IBD care. Full article

Background and Objectives: Multiple sclerosis (MS) is a chronic autoimmune, inflammatory, and neurodegenerative central nervous system disease. Neurodegeneration plays a central role in long-term disease progression. Materials and Methods: This cross-sectional study examined the relationship between neurodegenerative biomarkers, namely plasma neurofilament light chain (pNfL) levels and MRI-derived brain volume measurements, and clinical outcomes in 49 patients with relapsing–remitting multiple sclerosis (RRMS). Plasma NfL levels were quantified using Simoa technology, while MRI data was analyzed via FreeSurfer to measure volumes of grey and white matter, specific brain structures, and ventricular sizes. Cognitive performance was assessed using the Symbol Digit Modalities Test (SDMT) and Brief Visuospatial Memory Test-Revised (BVMT-R). Disability was evaluated using the Expanded Disability Status Scale (EDSS). Results: The results indicated significant positive correlations between SDMT scores and volumes of grey matter, white matter, and various subcortical structures, suggesting that preserved brain volume is linked to better cognitive performance. Negative correlations were observed between SDMT scores and ventricular volumes, as well as between SDMT scores and EDSS scores, implying that cognitive decline corresponds with structural brain deterioration and increased disability. No significant associations were found between BVMT-R scores and imaging data or disability measures. Plasma NfL levels showed significant correlations with early disease relapses and enlargement of the third and fourth ventricles, but not with brain volume, cognitive tests, or EDSS scores. Conclusions: These findings indicate that MRI-based brain volumetrics, particularly grey and white matter measures, are stronger indicators of cognitive function and disability in RRMS than plasma NfL. Full article

Background and Objectives: Multiple sclerosis (MS) is a chronic immune-mediated neurological disorder that primarily affects young adults and is frequently accompanied by psychiatric comorbidities such as depression and anxiety, both of which significantly diminish patients’ quality of life (QoL). This study investigated the effect of two oral disease-modifying therapies (DMTs), fingolimod and cladribine, on mental health and QoL in patients with relapsing-remitting MS (RRMS). The aim of the study was to compare levels of depression, anxiety, and health-related quality of life (HRQoL) in RRMS patients treated with fingolimod or cladribine, and to evaluate their associations with clinical and radiological parameters. Materials and Methods: Eighty RRMS patients aged 18 to 50 years with Expanded Disability Status Scale (EDSS) scores of 3.0 or less, no recent disease relapse, and no history of antidepressant use were enrolled. Forty patients were treated with fingolimod and forty with cladribine. Depression and anxiety were assessed using the Hamilton Depression Rating Scale (HDRS) and the Hamilton Anxiety Rating Scale (HARS). QoL was evaluated using the Multiple Sclerosis QoL-54 (MSQOL-54) instrument. Additional clinical data, including MRI-based lesion burden, EDSS scores, age, disease duration, and occupational status, were collected. Results: No statistically significant differences were observed between the two groups regarding HDRS and HARS scores (p > 0.05). However, patients treated with fingolimod had significantly higher scores in the Energy/Fatigue subdomain (7.55 ± 2.02 vs. 6.56 ± 2.57, p = 0.046) and Composite Mental Health (CMH) score (64.73 ± 15.01 vs. 56.00 ± 18.93, p = 0.029) compared to those treated with cladribine. No significant differences were found in the independent items of the MSQOL-54. A negative correlation was identified between total lesion load and QoL scores. Conclusions: Although fingolimod and cladribine exert comparable effects on depression and anxiety levels, fingolimod may be associated with better mental health outcomes and reduced fatigue in RRMS patients. Furthermore, lesion burden and clinical parameters such as age and EDSS score may independently influence QoL, regardless of the DMT used. Full article

Background/Objectives: Fatigue and cognitive impairment are common issues for People with Multiple Sclerosis (PwMS), affecting over 80% and 40–65%, respectively. The relationship between these two debilitating conditions is complex, with cognitive deficits exacerbating fatigue and vice versa. This study investigates the effects of a multimodal intervention combining cognitive rehabilitation and neuromodulation to alleviate fatigue and enhance cognitive performance in PwMS. Methods: The research employed multiple baselines across the subjects in a Single-Case Experimental Design (mbSCED) with a cohort of three PwMS diagnosed with Relapsing–Remitting MS. The intervention protocol consisted of a baseline phase followed by a four-week treatment involving transcranial direct current stimulation (tDCS) and cognitive training using RehaCom^® software (version 6.9.0). Fatigue levels were measured using the modified Fatigue Impact Scale (mFIS), while cognitive performance was evaluated through standardized neuropsychological assessments. Results: The multimodal protocol exhibited high feasibility and acceptability, with no dropouts. Individual responsiveness outcomes varied, with two PwMS showing significant decreases in fatigue and improvements in cognitive performance, particularly in the trained domains. Their motor performance and quality of life also improved, suggesting that the treatment had indirect beneficial effects. Conclusions: This study provides preliminary evidence for the potential benefits of integrating neuromodulation and cognitive rehabilitation as a personalized therapeutic strategy for managing fatigue and cognitive impairments in MS. Further research is needed to delineate the specific contributions of each intervention component and establish standardized protocols for clinical implementation. The insights gained may lead to more effective, tailored treatment options for PwMS. Full article

The present study aims to investigate the multi-year effects (5 years) of individualized whole-body vibration (WBV) on locomotion, postural control, and handgrip strength in a 68-year-old man with relapse remitting multiple sclerosis (PwRRMS). The dose–response relationship induced by a single session was quantified by determining the surface electromyographic activity (sEMG) of the participant. The participant wore an orthosis to limit the lack of foot dorsiflexion in the weakest limb during walking in daily life. The gait alteration during walking was assessed at 1, 2 and 3 km/h (without the orthosis) through angle–angle diagrams by quantifying the area, perimeter and shape of the loops, and the sEMG of leg muscles was recorded in both limbs. The evaluation of postural control was conducted during upright standing by quantifying the displacement of the center of pressure (CoP). The handgrip strength was assessed by measuring the force–time profile synchronized with the sEMG activity of upper arm muscles. The participant improved his ability to walk at higher speeds (2–3 km/h) without the orthosis. There were greater improvements in the area and perimeter of angle–angle diagrams for the weakest limb (Δ = 36–51%). The sEMG activity of the shank muscles increased at all speeds, particularly in the tibialis anterior of weakest limbs (Δ = 10–68%). The CoP displacement during upright standing decreased (Δ = 40–60%), whereas the handgrip strength increased (Δ = 32% average). Over the 5-year period of intervention, the individualized WBV improved locomotion, postural control and handgrip strength without side effects. Future studies should consider the possibility of implementing an individualized WBV in PwRRMS. Full article

The effective suppression of inflammation using disease-modifying therapies is essential in the treatment of multiple sclerosis (MS). Anti-CD20 monoclonal antibodies are commonly used long-term as maintenance therapies, largely due to the lack of reliable biomarkers to guide dosing and evaluate treatment response. However, prolonged use increases the risk of infections and other immune-mediated side effects. The unique ability of brain-derived blood extracellular vesicles (EVs) to cross the blood–brain barrier and reflect the central nervous system (CNS) immune status has sparked interest in their potential as biomarkers. This study aimed to assess whether blood-derived L1CAM⁺ EVs could serve as biomarkers of treatment response to rituximab (RTX) in patients with relapsing-remitting MS (RRMS). Serum samples (n = 25) from the baseline (month 0) and after 6 months were analyzed from the RTX arm of the ongoing randomized clinical trial OVERLORD-MS (comparing anti-CD20 therapies in RRMS patients) and were compared with serum samples from healthy controls (n = 15). Baseline cerebrospinal fluid (CSF) samples from the same study cohort were also included. EVs from both serum and CSF samples were characterized, considering morphology, size, and concentration, using transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA). The immunophenotyping of EV surface receptors was performed using flow cytometry with the MACSPlex exosome kit, while label-free quantitative proteomics of EV protein cargo was conducted using a proximity extension assay (PEA). TEM confirmed the presence of EVs with the expected round morphology with a diameter of 50–150 nm. NTA showed significantly higher concentrations of L1CAM⁺ EVs (p < 0.0001) in serum total EVs and EBNA1⁺ EVs (p < 0.01) in serum L1CAM⁺ EVs at baseline (untreated) compared to in healthy controls. After six months of RTX therapy, there was a significant reduction in L1CAM⁺ EV concentration (p < 0.0001) and the downregulation of TNFRSF13B (p = 0.0004; FC = −0.49) in serum total EVs. Additionally, non-significant changes were observed in CD79B and CCL2 levels in serum L1CAM⁺ EVs at baseline compared to in controls and after six months of RTX therapy. In conclusion, L1CAM⁺ EVs in serum showed distinct immunological profiles before and after rituximab treatment, underscoring their potential as dynamic biomarkers for individualized anti-CD20 therapy in MS. Full article

Background/Objectives: Inflammatory bowel disease (IBD) is characterized by chronic relapsing and remitting inflammation of the gastrointestinal tract. Fecal microbiota transplantation (FMT) has emerged as an FDA-approved treatment for recurrent Clostridioides difficile infections (CDIs), with promising potential in patients with IBD. This manuscript aimed to provide a comprehensive and updated review of the available literature on fecal microbiota transplantation, its clinical use in IBD in general, as well as in patients with IBD and CDI. Methods: An extensive literature search was performed from October 2024 to March 2025. All publications available within PubMed, Medline, Embase, Google Scholar, and Cochrane databases were reviewed. All original articles, case reports, review articles, systematic reviews, and meta-analyses were included. Qualitative and quantitative data were both extracted. Discussion: Intestinal microbiota is an integral part of the human body, and dysbiosis (an imbalance in the gut’s microbial community) has been linked with several pathologies. Dysbiosis in IBD is marked by reduced beneficial bacteria and increased pro-inflammatory pathogens, contributing to mucosal damage and immune dysregulation. FMT has emerged as a solution to dysbiosis, with the first case recorded in 1917. FMT has been successful in treating patients with CDI. The diagnostic value of the gut microbiome is currently being explored as a possible therapeutic approach to IBD. Several studies have assessed FMT in patients with IBD and CDI with promising results in both ulcerative colitis (UC) and Crohn’s disease (CD) but varying efficacy based on administration routes, donor selection, and processing methods. In the context of recurrent CDI in patients with IBD, FMT demonstrates a high cure rate and potential benefit in concurrently improving IBD activity. However, risks such as IBD flare-ups post-FMT remain a concern. Conclusions: FMT holds promising potential in the management of CDI in patients with IBD. By restoring microbial diversity and correcting dysbiosis, FMT offers a novel, microbiota-targeted alternative to conventional therapies. While data support its efficacy in improving disease remission, variability in outcomes underscores the need for standardized protocols and additional large-scale, controlled studies. Continued research efforts into donor selection, treatment regimens, and long-term safety will be critical to optimizing FMT’s role in IBD and CDI care as well as improving patient outcomes. Full article

Background/Objectives: Gut dysbiosis has been implicated in multiple sclerosis (MS), but microbial signatures remain inconsistent across studies. Machine learning (ML) algorithms based on global microbiome data integration can reveal key disease-associated microbial biomarkers and new insights into MS pathogenesis. This study aimed to investigate gut microbial signatures associated with MS and to evaluate the potential of ML for diagnostic applications. Methods: Fecal samples from 29 relapsing–remitting MS patients during exacerbation and 27 healthy controls were analyzed using 16S rRNA gene sequencing. Differential abundance analysis was performed, and data were integrated with 29 published studies. Four ML models were developed to distinguish MS-associated microbiome profiles. Results: MS patients exhibited reduced levels of Eubacteriales (p = 0.037), Lachnospirales (p = 0.021), Oscillospiraceae (p = 0.013), Lachnospiraceae (p = 0.012), Parasutterella (p = 0.018), Faecalibacterium (p = 0.004), and higher abundance of Lachnospiraceae UCG-008 (p = 0.045) compared to healthy controls. The Light Gradient Boosting Machine classifier demonstrated the highest performance (accuracy: 0.88, AUC-ROC: 0.95) in distinguishing MS microbiome profiles from healthy controls. Conclusions: This study highlights specific microbiome dysbiosis in MS patients and supports the potential of ML for diagnostic applications. Further research is needed to elucidate the mechanistic role of these microbial alterations in MS progression and their therapeutic utility. Full article

Background: Cognitive impairment (CI) is a common and disabling symptom in patients with relapsing–remitting multiple sclerosis (RRMS), potentially emerging at any stage, including preclinical phases. Despite its impact on quality of life, CI often goes unrecognized, as clinical follow-up typically focuses on motor and sensory symptoms. Validated tools, such as the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) and patient-reported outcomes (PROs), should be integrated into routine evaluations beyond the Expanded Disability Status Scale (EDSS). Objective: The objective of this study was to evaluate cognitive impairment and quality of life in patients with RRMS using the BICAMS and PROs. Methods: This cross-sectional, descriptive study included patients with RRMS under follow-up at a tertiary hospital in San Luis Potosí, Mexico. Participants underwent cognitive screening with the BICAMS battery and completed the MSQoL-54 (quality of life), FSMC (fatigue), and MSIS-29 (functional impact) scales. Statistical analyses included ANOVA, the Kruskal–Wallis test, and Pearson correlations. Results: Nineteen patients were evaluated (73.7% female, mean age 36.5 ± 8.9 years). BICAMS results showed variable cognitive performance, with no significant differences across treatment groups for processing speed (p = 0.222), verbal memory (p = 0.082), or visuospatial memory (p = 0.311). A significant correlation was found between verbal and visuospatial memory (r = 0.668, p = 0.002). Total quality of life differed significantly across treatments (F = 8.007, p = 0.029), with a strong correlation between overall quality of life and general health perception (r = 0.793, p < 0.001). Fatigue and MSIS scores showed no association with treatment. Conclusions: Cognitive impairment is common in RRMS and can be detected using brief assessment tools, such as the BICAMS. Incorporating cognitive screening and PROs into clinical practice is essential to guide comprehensive management. Full article

Background: Cutaneous lichen planus (CLP) is a chronic inflammatory T cell-mediated disease driven by a mixed Th1 and Th2 lymphocyte population, for which many of the currently available treatments have poor efficacy. Aim: The aim of this study was to indicate the clinical success of dupilumab administration after two years of treatment in a case of longstanding CLP and to perform a review of the medical literature related to the use of dupilumab in different dermatologic settings and in CLP. Case presentation: One 26-year-old woman with a previous history of atopic dermatitis had a long-lasting skin condition, referred to as a suspected lichen, which started when she was 7 years old. Her disease exhibited a relapsing–remitting course with severe bouts of pruritus over a very long period. The final histological diagnosis of CLP was confirmed at the age of 26. Starting dupilumab (injected subcutaneously at a dose of 600 mg followed by a maintenance dose of 300 mg every two weeks) resolved the skin scenery of this patient, who is currently in full remission. Conclusions: The remarkable recovery from CLP obtained via treatment with dupilumab in this single-patient case study emphasizes the potential therapeutic implications of targeting the Th2 pathway in this skin disorder. Full article