Search Results (450)

Background/Objectives: Cytokine-mediated immune dysregulation contributes to the heterogeneity of multiple sclerosis (MS). Interleukin-18 (IL-18) and interleukin-8 (IL-8) are involved in distinct inflammatory pathways; however, their genetic contributions to disease susceptibility and radiological activity remain incompletely defined. Methods: In this study, 98 relapsing–remitting MS (RRMS) patients and 98 healthy controls were genotyped for IL-18 and IL-8 variations using PCR-based methods. Clinical data and MRI findings were analyzed in the MS cohort. Associations with disease susceptibility, clinical severity (EDSS), and MRI activity were evaluated using regression analyses. Results: IL-18 (−137 G/C) and IL-8 variations were significantly associated with MS susceptibility. The G allele of IL-18 (−137), the T allele of IL-8 (−251), and the C allele of IL-8 (+781) were more frequent in MS patients. No significant associations were observed between cytokine variations and clinical severity measures. However, IL-18 (−137) variation was significantly associated with higher baseline MRI lesion burden, with C allele carriers showing increased lesion counts. In addition, IL-8 (−251 AA genotype) was independently associated with increased annual lesion development. These findings were confirmed in multivariable regression analyses. Conclusions: IL-18 and IL-8 gene variations contribute to MS through distinct but complementary mechanisms. IL-18 appears to be primarily involved in disease susceptibility and baseline inflammatory burden, whereas IL-8 is more closely associated with ongoing radiological activity. These results highlight the importance of integrating genetic and imaging biomarkers to better understand disease heterogeneity in MS. Full article

Background/Objectives: Multiple sclerosis (MS) is a chronic, demyelinating and neurodegenerative disease frequently associated with dysphagia, nutritional imbalances, and alterations in body composition. This study aims to describe the anthropometric profile and body composition in people with MS, estimate the risk and type of dysphagia, analyse dietary intake and habits, and evaluate the evolution of these parameters over six months. Methods: This descriptive analytical longitudinal study included 30 patients with MS (20 women, 10 men), with a median age of 53.3 years at baseline and 54.0 years at final assessment. The prevalence of dysphagia risk was determined, dietary patterns and body composition were characterised, and their interactions were explored through two assessments conducted six months apart. Results: Overall, 90% of the sample had relapsing–remitting MS (RRMS). At both the initial and final assessments, the median BMI was above 25 kg/m² and a high prevalence of dysphagia risk (63.3% and 76.7%), particularly for liquids. Frequent inadequacies were observed in the intake of certain macronutrients and micronutrients, including energy, fibre, potassium and magnesium. Likewise, the analysis by food groups revealed low adherence to recommendations, particularly for fruits, cereals, legumes, fish and lean meats. No significant differences were detected between the two time points. Conclusions: Dysphagia, dietary intake, habits, and body composition are interconnected dimensions in MS; systematically integrating nutritional assessment and dysphagia screening into clinical practice would contribute to a more comprehensive management and to improvements in swallowing disorders and nutritional status in people with MS. Full article

Background and Objectives: Visual evoked potentials (VEPs) are a simple, noninvasive method for detecting subclinical visual pathway involvement in multiple sclerosis. This study investigated the frequency of VEP abnormalities and their associations with baseline clinical, radiological, and cerebrospinal fluid (CSF) features in treatment-naïve patients with clinically isolated syndrome (CIS) or early relapsing-remitting multiple sclerosis (RRMS) without prior optic neuritis. Materials and Methods: We retrospectively reviewed newly diagnosed, treatment-naïve CIS/early RRMS patients evaluated between January 2022 and July 2024 who underwent CSF analysis. Pattern-reversal VEPs were recorded under standardized conditions. VEP abnormalities were analyzed as any or bilateral, and associations were assessed using group comparisons and multivariable logistic regression. Results: In 101 patients (mean age 31.8 ± 9.7 years; 72% female; median EDSS 1.0), latency prolongation occurred in 69 (42 any,27 bilateral) and amplitude reduction in 33 (22 any, 11 bilateral). Among patients with latency prolongation, both the number of OCB bands and the IgG index were higher (bilateral p = 0.032; any p = 0.007). In multivariable analysis, male sex (p = 0.032) and pyramidal/brainstem-onset presentation (p = 0.006) were independently associated with any amplitude reduction; neither was associated with latency abnormalities. Conclusions: VEP abnormalities are common early in the disease, even without a history of optic neuritis. Male sex and pyramidal/brainstem-onset presentation were associated with reduced amplitude, suggesting that amplitude decrease may reflect early tissue dysfunction and may be related to adverse baseline clinical features. Associations between intrathecal immune activation and prolonged latency may indicate subclinical demyelination of the visual pathways related to inflammatory activity. Larger longitudinal studies are needed to clarify the clinical significance of VEP abnormalities in early RRMS. Full article

Background/Objectives: Gut microbiota (GM) dysbiosis has been implicated in multiple sclerosis (MS) pathogenesis, influencing inflammation and neurodegeneration, but findings remain inconsistent due to environmental and methodological variability. This study aimed to identify possible microbial biomarkers of MS status and disease severity by profiling gut microbiota and short-chain fatty acid (SCFA) patterns in people with relapsing–remitting MS (pwRRMS), using household-matched healthy controls (HC) to minimize environmental variability. Methods: Twenty-four pwRRMS and their respective household-matched healthy controls (HC) were enrolled, with dietary and lifestyle habits monitored. GM composition was assessed by 16S rRNA gene sequencing, and fecal SCFAs were quantified using gas chromatography–mass spectrometry. PwRRMS were stratified by Expanded Disability Status Scale (EDSS) and Multiple Sclerosis Severity Score (MSSS). Results: β-diversity did not differ between groups. However, α-diversity was significantly reduced in pwRRMS, particularly in those with greater disability. Reduced diversity was associated with lower abundance of butyrate-producing genera (Roseburia, Faecalibacterium, Coprococcus) and enrichment of Oscillibacter and UBA1819, alongside a downward trend in fecal butyrate and propionate levels. Conclusions: RRMS and greater disease severity are associated with gut microbial alterations characterized by reduced SCFA-producing bacteria. Despite limitations including small sample size and sex imbalance, the household-matched design strengthens internal validity. Our findings highlight the potential of targeting the gut microbiota, an accessible compartment within the gut–brain axis, for MS management. Full article

Background: Serum neurofilament light chain (sNfL) is an established biomarker of neuroaxonal damage in multiple sclerosis (MS). Despite its prognostic utility, patient awareness of its clinical application remains poorly characterized. The objective of this study was to assess the acceptance of sNfL monitoring among patients with early-stage relapsing–remitting MS (RRMS) and identify factors predicting their willingness to adopt this tool. Methods: This non-interventional, cross-sectional study was conducted across 16 neuroimmunology clinics. We included RRMS patients with a disease duration of ≤3 years receiving disease-modifying therapy. Acceptance was assessed following a standardized educational tutorial. Multivariable logistic regression was employed to identify predictors of patient acceptance. Results: The study included 144 patients (mean age 37.6 [SD 10.3] years, 69.4% female). Only 19.4% (n = 28) had prior awareness of sNfL. However, after the tutorial, 84.0% (n = 121) expressed willingness to adopt sNfL testing. Furthermore, 62.5% (n = 90) indicated that normal sNfL levels would provide emotional reassurance between clinical visits. Patients willing to undergo testing showed higher disease knowledge, less treatment regret, and better physical quality of life and cognitive performance. In the multivariable analysis, higher disease knowledge (OR = 1.52, 95%CI 1.16–1.99; p = 0.002) and lower symptom burden (OR = 0.96, 95%CI 0.93–0.99; p = 0.038) were associated with greater acceptance. Conclusions: Patients demonstrate high receptivity to sNfL monitoring when provided with adequate clinical context. Because disease knowledge is a primary driver of acceptance, personalized educational initiatives may be a complementary strategy to facilitate the integration of precision biomarkers into MS management. Full article

Background/Objectives: Real-world evidence on ofatumumab (OFA) beyond 12 months remains limited in relapsing–remitting multiple sclerosis (RRMS). We assessed 24-month effectiveness and safety, compared treatment-naïve and previously treated patients, and explored predictors of failure to achieve No Evidence of Disease Activity-3 (NEDA-3). Methods: This multicenter retrospective cohort study included adult RRMS patients treated with OFA in routine clinical practice. Effectiveness analyses were restricted to patients with complete 24-month follow-up and full clinical and magnetic resonance imaging (MRI) assessment (complete-case analysis). Outcomes included relapses, MRI activity, Expanded Disability Status Scale (EDSS) progression, NEDA-3, and adverse events (AEs). Exploratory multivariable logistic regression was used to assess baseline predictors of NEDA-3 non-achievement. Results: Of 258 patients who initiated OFA, 148 had completed 24-month clinical and MRI follow-up and were evaluable for effectiveness. Over 24 months, 71.5% achieved NEDA-3; relapses occurred in 15.5% of patients, MRI activity in 15.5%, gadolinium-enhancing lesions (GELs) in 4.7%, and EDSS progression in 17.6%. Disease activity was minimal during months 12–24, with relapses in 2.7%, MRI activity in 2.0%, and no GELs. In unadjusted analyses, no statistically significant differences were observed between treatment-naïve and previously treated patients. Higher baseline EDSS was associated with failure to achieve NEDA-3. In the 24-month safety subgroup, AEs were recorded in 28.4% of patients; infections occurred in 26.4% of patients (all grade 1–2), and no serious adverse events were observed. Conclusions: In this multicenter real-world cohort, OFA was associated with low inflammatory disease activity over 24 months in RRMS patients with complete follow-up. These findings should be interpreted cautiously because the effectiveness analysis was restricted to a complete-case cohort and safety data were collected retrospectively. Full article

Background/Objectives: Multiple Sclerosis (MS) is a chronic immune-mediated disorder characterized by neuroinflammation and neurodegeneration. Increasing evidence implies the kynurenine pathway (KP) in the MS pathophysiology; however, data from Mexican populations are lacking. This exploratory study aimed to characterize central and circulating KP metabolites in Mexican patients with MS and to investigate potential genetic variants in KP-related genes. Methods: Serum concentrations of kynurenic acid (KYNA) and 3-hydroxykynurenine (3-HK), as well as cerebrospinal fluid (CSF) levels of KYNA, quinolinic acid (QUIN), interleukin-4 (IL-4), and interleukin-6 (IL-6), were determined in treatment-naïve relapsing-remitting MS (RRMS), primary progressive MS (PPMS), and treated PMS patients. Serum levels were compared with those of healthy controls, and CSF findings contrasted with those of non-MS neurological patients and individuals with neurocysticercosis (NCC). Public whole-exome datasets were analyzed for variants in KP-related genes, and target exome sequencing was performed in three Mexican patients with MS. Results: Serum concentrations of KYNA and 3-HK were decreased in MS patients compared with healthy controls. CSF KYNA and QUIN levels did not differ significantly among MS subtypes or the non-MS neurological group, but they were lower than those observed in NCC. IL-4 and IL-6 were detectable in MS CSF samples, supporting the presence of intrathecal inflammation. Genetic and bioinformatic analyses identified variants in genes encoding KP enzymes in both public MS datasets and in Mexican patients with MS. Conclusions: These findings indicate an altered KP metabolism in Mexican MS patients, particularly during the relapse phase, and suggest a possible contribution of genetic variability. Further large-scale studies are needed to confirm these observations and to determine the functional implications of KP-related genetic variants in MS. Full article

Background: Circulating cytokines and their soluble receptors in body fluids have been implicated in the pathogenesis of multiple sclerosis (MS). Alterations in serum levels of pro- and anti-inflammatory cytokines and/or their soluble receptors can dysregulate central nervous system (CNS) signaling pathways and, therefore, may serve as potential biomarkers for the diagnosis of MS. Therefore, the primary end-point of this study is to investigate the utility of various cytokines and their soluble receptors as diagnostic biomarkers in MS. The secondary outcome is also to assess whether these cytokines are useful in differentiating the severity of MS. Methods: In this case–control study, we compared a panel of pro-inflammatory interleukins (ILs), including IL18 and tumor necrosis factor-alpha (TNFα), soluble IL receptors (sIL7Rα and sIL2Rα), and insulin-like growth factor-1 (IGF-1) in 45 MS patients and in 45 healthy control individuals matched for sex and age. Associations of these biomarkers with age, disease severity (Expanded Disability Status Scale [EDSS]), disease duration, and age at first MS symptom onset were also assessed. Results: Serum levels of cytokines and soluble IL receptors were elevated in MS patients compared to healthy controls. IGF-1 was lower (p < 0.001) in the MS patients than in the healthy individuals. The serum level of IGF-1 was higher (p < 0.01) in the remitting-relapsing phase compared to the primary progression and secondary progression stages. Similarly, only IGF-1 was more elevated (p < 0.01) in the mild stage compared to the moderate stage based on the EDSS score. Receiver operating characteristic (ROC) curve analysis demonstrated that IL18 had excellent discriminatory power for the diagnosis of MS (p < 0.001), with an area under the curve (AUC) of 0.96 ± 0.017, followed by IGF-1 (p < 0.001), which showed strong diagnostic performance (AUC = 0.873 ± 0.037). Soluble (s) IL2Rα exhibited fair diagnostic accuracy (p < 0.001; AUC = 0.717 ± 0.054). In contrast, sIL7Rα and TNFα showed poor discriminatory power despite statistical significance (p < 0.01), with AUC values of 0.675 ± 0.057 and 0.687 ± 0.056, respectively. Results of regression analysis revealed that EDSS, duration of disease, and use of any treatment had no impact on the cytokines. Similarly, no significant correlations were noted between these confounders and cytokines, except a moderate negative correlation (−0.418) between IGF-1 and EDSS. Conclusions: IL18 and IGF-1 have the potential to be used as biomarkers in distinguishing MS from healthy individuals. However, both biomarkers failed to demonstrate the discrimination between various phenotypic patterns of disease, limiting their utility for disease stratification. Future studies with larger, longitudinal cohorts and multi-marker panels are warranted to validate these results and to explore whether combining cytokines with imaging or genetic markers can improve prognostic precision. Full article

Multiple sclerosis (MS) is an autoimmune and demyelinating disease of the central nervous system (CNS). By acting on the immune system, disease-modifying therapies (DMTs) can control disease activity, but they indirectly increase susceptibility to infections, so different vaccines are necessary to prevent it. DMTs may potentially affect vaccine-induced seroconversion. We aim to analyse the response to the hepatitis B virus (HBV) vaccine (Engerix-B) in relapsing–remitting MS patients (RRMS) using these therapies because the scientific literature remains limited in this area. A retrospective observational study of RRMS patients vaccinated against HBV was conducted. Acquired immunity after vaccination was determined, and an analysis of immunogenicity was conducted based on the type of DMT (immunomodulators/immunosuppressants), vaccine doses, total lymphocyte count (TLC), age, and sex. 200 patients were included, with a mean age 47.79 years, and 140 (70%) were women. A lower vaccine response was observed in patients treated with immunosuppressive DMTs (51.8%, p < 0.001), particularly with fingolimod (32.4%, p < 0.001), and a higher response was seen with immunomodulators like teriflunomide and interferon-β1a (100%, p < 0.001). Using logistic regression, a model was obtained that included the number of vaccine cycles, lymphopenia and type of DMT associated with the response to the HBV vaccine. It is necessary to adapt HBV vaccination protocols for MS patients, considering the type of DMT used and baseline immune status. Full article

Background: Radiologically isolated syndrome (RIS) is defined by MRI findings that are suggestive of multiple sclerosis (MS) in the absence of prior clinical demyelinating events. We aimed to compare the health-related quality of life (HRQoL) between RIS and relapsing–remitting MS (RRMS) after adjusting for fatigue, cognition, and psychological distress, and to contextualize generic HRQoL, relative to healthy controls. Methods: In this cross-sectional analysis of the baseline data, 30 RIS, 29 RRMS, and 30 healthy controls were analyzed. MS-specific HRQoL (patients only) was assessed with the Functional Assessment of Multiple Sclerosis (FAMS), and generic HRQoL (all participants) was assessed with the EuroQol-5D (EQ-5D) visual analogue scale and utility index. Multi-variable linear regression models with robust (HC3) standard errors were used, adjusting for demographics, fatigue impact, cognitive performance, and psychological distress. Results: The FAMS totals were similar in RIS vs. RRMS (median 167.5 vs. 164.0; p = 0.694) and remained non-different after adjustment (β= −2.37, 95% CI −10.18 to 5.44; p = 0.544). EQ-5D outcomes showed an unadjusted gradient across groups, but adjusted differences relative to RIS were not statistically significant. Greater fatigue impact was associated with poorer HRQoL across all models (all p < 0.001). Psychological distress was associated with lower FAMS (β = −14.53; p < 0.001) but not with EQ-5D outcomes. Conclusions: HRQoL in RIS was comparable to RRMS, and fatigue impact was the most consistent correlate of poorer HRQoL. Full article

Background and Objectives: Sexual dysfunction (SD) is common in multiple sclerosis (MS) but remains under-recognized in routine care. This study aimed to quantify the burden of SD in men and women with relapsing–remitting MS (RRMS), describe sex-stratified patterns across primary/secondary/tertiary domains, and examine associations with fatigue and MS-related health-related quality of life (HRQoL). Materials and Methods: In this cross-sectional observational study, RRMS participants were voluntarily recruited online via a QR code linking to a Google Forms survey. Men completed the International Index of Erectile Function-5 (IIEF-5), and women the Female Sexual Function Index (FSFI). MS-specific SD domains were assessed using the Multiple Sclerosis Intimacy and Sexuality Questionnaire (MSISQ), alongside the Fatigue Severity Scale (FSS) and the Multiple Sclerosis Quality of Life questionnaire (MSQOL-54). Sex differences were tested using parametric/non-parametric methods as appropriate, with false discovery rate (FDR) and Bonferroni adjustments for multiple comparisons. Results: Thirty-seven participants were included (16 men; 21 women). Mean age did not differ by sex (35.9 ± 4.0 vs. 38.9 ± 10.4 years; p = 0.23). All participants reported at least some degree of difficulty across MSISQ domains. Among men, 87.5% screened positive for erectile dysfunction within this sample (mild 37.5%, mild-to-moderate 12.5%, moderate 12.5%, severe 25.0%). When dysfunction type was defined as the highest MSISQ domain score, secondary SD was most frequent in both sexes (75.0% men; 76.2% women; p = 0.49). Women showed higher secondary domain scores at the uncorrected level (p = 0.04), but this did not survive FDR correction. In HRQoL and symptom measures, women reported markedly higher fatigue (FSS 46.1 ± 12.4 vs. 25.5 ± 12.7; p_FDR < 0.001) and poorer physical health indices, including pain-related outcomes. Conclusions: SD has represented a substantial burden within this RRMS sample, with secondary domain predominance in both sexes, highlighting the clinical relevance of symptom-related and functional interference. These findings support the value of multidimensional sexual health assessment in clinical research settings and may be relevant for clinical assessment and future research in MS. Full article

Background: The eye has shown potential as a reliable, readily accessible and clinically relevant site for investigating patients with multiple sclerosis (pwMS). Optical coherence tomography angiography (OCTA) shows promise in revealing new metabolic and vascular elements driving multiple sclerosis (MS) disease pathology. This study aimed to explore correlations between OCTA parameters and clinical characteristics in newly diagnosed relapsing–remitting MS (RRMS) patients. Methods: In this cross-sectional study, forty-one newly diagnosed RRMS patients underwent comprehensive evaluations, including neurological examinations, functional and cognitive tests (9-Hole Peg Test, Montreal Cognitive Assessment), and OCT/OCTA scans. Multiple regression analyses assessed correlations between OCT/OCTA parameters and baseline clinical characteristics. Results: Lower superficial capillary plexus (SCP) vessel density was associated with longer disease duration, higher EDSS scores (visual, pyramidal, cerebellar, ambulation), and impaired 9-Hole Peg Test performance, especially in the non-dominant hand. Higher values of choriocapillaris (CC) flow voids correlated with worse cognitive performance (MoCA). Structural OCT parameters showed limited clinical correlations. Conclusions: OCTA-derived parameters are associated with disability, fine motor function, and cognitive performance in newly diagnosed RRMS patients without prior ON. These findings suggest that retinal vascular alterations may reflect early neurodegenerative processes and provide complementary information beyond structural OCT metrics. OCTA may represent a sensitive, non-invasive imaging biomarker for patient assessment in early MS. Full article

Background/Objectives: Ofatumumab is a fully human anti-CD20 monoclonal antibody approved for the treatment of relapsing forms of multiple sclerosis (MS). While its efficacy and safety have been demonstrated in clinical trials, real-world data focusing on laboratory changes and detailed immunophenotyping during treatment remain limited. The objective of this study was to assess routine laboratory parameters and immunophenotyping profiles in ofatumumab-treated patients in a real-world setting. Methods: We conducted a retrospective, single-center real-world study including 59 patients with relapsing–remitting MS treated with ofatumumab. Routine laboratory parameters were analyzed at the baseline and 6–12 months after treatment initiation. Immunophenotyping by flow cytometry was available for a subset of 29 patients. Infections were assessed during a follow-up period of at least six months. Paired comparisons were performed using the Wilcoxon signed-rank test. Results: Ofatumumab induced a profound and sustained depletion of CD19+ B cells (p < 0.001). Total T cells, CD4+ and CD8+ T-cell counts, the CD4/CD8 ratio, and natural killer (NK) cells remained largely stable over time. NK cells and helper T cells showed a numerical increase without statistical significance. IgM levels and relative lymphocyte percentages showed a statistically significant decrease compared with baseline (p = 0.047 and p = 0.016, respectively), while remaining within reference ranges. Other routine laboratory parameters remained stable. Reported infections were infrequent and predominantly mild. Conclusions: In this real-world cohort, ofatumumab demonstrated a favorable immunological and laboratory profile consistent with its known mechanism of action. These findings suggest that routine laboratory monitoring is sufficient for most patients, while immunophenotyping may be reserved for selected clinical scenarios. Further prospective studies integrating clinical and radiological outcomes are needed to better define the clinical relevance of these immunological findings. Full article

Background/Objectives: Response heterogeneity limits the implementation of dry needling for spasticity in multiple sclerosis (MS). This secondary analysis aimed to identify early responders and explore predictors of response. Methods: We conducted a responder analysis of a pilot randomized, double-blind, sham-controlled trial (NCT05956119) including 18 ambulatory MS patients with spasticity, randomized to a single session of dry needling (n = 9) or sham (n = 9). Sensitive responder criteria were defined as improvement ≥ 2.0 s in Timed Up-and-Go, ≥5 points in MSQOL-54 physical component, or ≥10% in 25-Foot Walk Test at 4 weeks. Results: Using these criteria, 33.3% (3/9) of dry needling recipients were classified as responders versus 0% (0/9) in the sham group (p = 0.214). Responders were more frequently observed among participants with relapsing–remitting MS (100% vs. 40%, p = 0.090) and lower baseline disability (Expanded Disability Status Scale 3.4 vs. 4.4). A positive association was observed between baseline pyramidal subscore and physical quality-of-life change, although this did not reach statistical significance (r = 0.52, p = 0.150) in the active group. Conclusions: Approximately one-third of participants met predefined responder criteria following dry needling; however, these findings should be interpreted as preliminary signals derived from an exploratory, underpowered pilot analysis. These results are hypothesis-generating and require confirmation in adequately powered trials. Full article

Cognitive impairment (CI) is a common and disabling manifestation of multiple sclerosis (MS), yet it remains underdiagnosed in clinical settings. This study aims to identify the volumetric MRI markers of CI in MS patients. A total of 79 MS patients were enrolled; after exclusions, 63 with relapsing-remitting MS (RRMS) and 7 with primary progressive MS were analyzed. All participants underwent neuropsychological testing (CVLT, BVRT, CTT, VFT, VST, and SDMT). Brain volumes were analyzed using FreeSurfer. In RRMS, 59% had CI (35% single-domain, 24% multidomain). Multidomain CI was linked to reduced left cerebellar white matter and bilateral pallidum volumes, slight choroid plexus enlargement, and higher lesion volume versus cognitively preserved patients. Significant correlations were found between brain volumes and cognitive test scores: cerebellar and cerebral white matter, corpus callosum, subcortical gray matter, and thalamus volumes correlated positively with measures of processing speed, memory, and verbal fluency, while higher lesion load and larger choroid plexus volumes were associated with poorer cognitive performance. CI in MS is linked to both global and regional brain atrophy, as well as lesion load. Volumetric MRI, including choroid plexus analysis, may represent candidate imaging correlates of CI; however, longitudinal and externally validated studies are needed to confirm their predictive value and clinical utility. Full article