Semra Mungan

Objectives: The neutrophil-to-lymphocyte ratio (NLR) is an easily obtainable blood-based marker reflecting systemic inflammation and immune activation. Its temporal behavior during relapses, corticosteroid treatment, and recovery in relapsing-remitting multiple sclerosis (RRMS) remains unclear. The objective of this study was to evaluate longitudinal changes in NLR and disability measured by Expanded Disability Status Scale (EDSS) across relapses, end of corticosteroid therapy, and one-month follow-up in RRMS. Methods: A total of 20 patients with RRMS relapses and 60 healthy controls were included in our study. Blood samples were collected once from controls and three times from patients: before corticosteroid therapy (BT), at the end of treatment (ET), and one month after therapy (1 M). NLR was calculated from automated complete blood counts. EDSS was scored by a trained neurologist at each visit. Statistical analyses were performed using SPSS. Correlation between NLR and EDSS was evaluated using repeated-measures correlation (rmcorr) in RStudio. Results: NLR was significantly higher in BT vs. controls (p=0.009) and increased further at ET (p<0.001), followed by a decline at 1 M (p=0.034). EDSS scores decreased significantly at ET and remained lower at 1 M. Receiver Operating Characteristic (ROC) analysis showed moderate discrimination for BT vs. control groups (AUC=0.696, p=0.009) and ET vs. BT (AUC=0.727, p=0.014), while 1 M vs. ET was not significant (AUC=0.626, p=0.172). Conclusions: NLR dynamically reflects both inflammatory activity and corticosteroid-induced immune modulation in RRMS. Although its diagnostic power is modest, NLR is a practical, cost-effective biomarker that may complement clinical and radiological tools in monitoring relapse and treatment response.

Multiple sclerosis (MS) is associated with an elevated risk of cardiovascular complications primarily due to endothelial dysfunction. Asymmetric dimethylarginine, an endogenous inhibitor of nitric oxide synthase, is a biomarker for endothelial dysfunction. This study aimed to examine the association between serum asymmetric dimethylarginine (ADMA) levels and carotid intima-media thickness (CIMT) in patients with MS compared with healthy controls. This study included 50 patients with MS and 50 healthy controls. Serum ADMA concentrations were quantified and CIMT was evaluated using Doppler ultrasonography. Statistical analyses included correlation and multivariate regression modeling. In this cross-sectional study, elevated levels of ADMA were found to be associated with increased subclinical carotid atherosclerosis in patients with MS. These findings suggest that ADMA may serve as a candidate biomarker for cardiovascular risk stratification. However, further prospective longitudinal studies are necessary to validate these findings and to establish the predictive value of ADMA in this population. Patients with MS exhibited significantly elevated ADMA levels (median: 15, 053 vs 8, 818 ng/L, P < .05) and increased CIMT (median: 0.60 [0.50–0.78] vs 0.50 [0.40–0.70] mm, P < .05) than controls. A positive correlation was observed between ADMA and CIMT ( R = 0.56, r ² = 0.31, P < .01). In multivariate regression analysis, ADMA was the only significant independent predictor of CIMT ( P < .001).

Journal of Medical Internet Research - International Scientific Journal for Medical Research, Information and Communication on the Internet #Preprint #PeerReviewMe: Warning: This is a unreviewed preprint. Readers are warned that the document has not been peer-reviewed by expert/patient reviewers or an academic editor, may contain misleading claims, and is likely to undergo changes before final publication, if accepted, or may have been rejected/withdrawn. Readers with interest and expertise are encouraged to sign up as peer-reviewer, if the paper is within an open peer-review period. Please cite this preprint only for review purposes or for grant applications and CVs (if you are the author). Background: Large language model-based chatbots are increasingly used by the public to access medical information. While these tools offer considerable potential in terms of accessibility and scalability, their accuracy, transparency, and clarity remain insufficiently evaluated for rare and diagnostically complex conditions such as myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). Objective: This study aimed to evaluate the quality, comprehensibility, transparency, and readability of responses generated by widely used AI chatbot platforms in response to a standardized, patient-centered question about MOGAD. Methods: We conducted a cross-sectional content analysis using the query: “What is MOGAD, and how is MOGAD treated?” Ten widely used chatbot platforms were selected to reflect diversity in architecture, access model, and functional design. Responses were collected on the same day, anonymized, and independently evaluated by seven blinded neurologists. Validated instruments were used, including DISCERN (treatment quality), PEMAT-P (understandability), Web Resource Rating (WRR; citation transparency), and two readability metrics: Flesch–Kincaid Grade Level (FKGL) and Coleman–Liau Index (CLI). Chatbots were also compared by access type (free vs paid) and functional focus (conversation-based vs search-based). Inter-rater reliability was assessed using intraclass correlation coefficients (ICCs). Results: Significant differences were observed across platforms in DISCERN, PEMAT-P, and WRR scores (all p < 0.001). Paid chatbots demonstrated higher treatment quality (p = 0.020) and citation transparency (p = 0.001) compared to free versions. Search-based models produced more understandable responses than conversation-based ones (p = 0.035). However, none of the chatbot responses achieved the recommended readability threshold for public-facing health communication (FKGL < 8). Inter-rater agreement was excellent across all expert-rated measures (ICC ≥ 0.838). Conclusions: AI chatbot responses to patient queries about MOGAD vary widely in quality, clarity, and transparency. These findings highlight the need for structured benchmarking, transparent evaluation frameworks, and thoughtful oversight in the use of generative AI tools for digital health communication, particularly in the context of rare and clinically complex diseases.

Multiple sclerosis (MS) is an autoimmune neurodegenerative disorder, with relapsing–remitting MS (RRMS) being the most common subtype. Interferon-γ (IFN-γ) plays a dual role in MS pathogenesis. MicroRNAs (miRNAs) have emerged as potential diagnostic biomarkers. This study examined the effect of relative expression of hsa-miR-24-3p and hsa-miR-181d-3p, plasma IFN-γ levels, and the IFNG rs2069727 T/C variant on MS risk, evaluating their interrelationships and diagnostic potential. This case–control study comprised two overlapping groups—a genetic polymorphism group (330 RRMS, 330 healthy controls (HCs)) and a miRNA group (25 glatiramer acetate (GA)-treated RRMS patients, 25 treatment-naïve RRMS patients, and 25 HCs)- collected at the Ankara Bilkent City Hospital Neurology Polyclinic. The IFNG rs2069727 T/C variant did not display a statistically significant disparity between RRMS patients and HCs. Significantly elevated hsa-miR-24-3p and hsa-miR-181d-3p relative expression levels were observed in GA-treated and treatment-naïve RRMS patients compared to HCs. Conversely, age-adjusted plasma IFN-γ concentrations were markedly lower in GA-treated and treatment-naïve RRMS patients versus HCs. Individuals with low plasma IFN-γ levels (≤ 1.311 pg/mL) demonstrated significantly elevated hsa-miR-24-3p relative expression compared to the high IFN-γ group (> 1.311 pg/mL). Conversely, subjects with low hsa-miR-181d-3p levels (≤ 2.90) exhibited significantly higher plasma IFN-γ concentrations relative to those with high hsa-miR-181d-3p levels (> 2.90). In the GA-treated group, EDSS negatively correlated with age-adjusted plasma IFN-γ. This study identified age-adjusted plasma IFN-γ, hsa-miR-24-3p, and hsa-miR-181d-3p expression as potential blood-based biomarkers for RRMS diagnosis and analyzed them alongside disability scores. The miRNAs in this study can be further evaluated as prospective therapeutic targets.

Multiple sclerosis (MS) is a chronic, demyelinating disorder of the central nervous system that is widely accepted to result from a complex interplay of genetic and environmental factors. The involvement of clusterin in neurodegenerative and autoimmune diseases has been highlighted, but its role in MS remains unclear. This study aimed to investigate the association of four single nucleotide polymorphisms (SNPs) in the clusterin gene (CLU) with MS susceptibility. The study group consisted of 310 patients with RRMS (pwRRMS) and 310 controls. 25 treatment-naïve pwRRMS, 25 pwRRMS on fingolimod treatment and 25 controls composed a subgroup for further analysis. The genotypes of 4 CLU SNPs were determined using either restriction endonuclease digestion following PCR (rs11136000 & rs3087554) or the real-time PCR method using TaqMan genotyping assays (rs2279590 & rs1532278). Plasma clusterin concentration was determined by ELISA in the subgroup (n = 75). Our results revealed that CLU rs3087554 C allele (p = .008) and TC + CC genotype were significantly associated with RRMS (p = .002). Furthermore, haplotype analysis has also shown that T-C-T-T haplotype was associated with RRMS (p < .001). Moreover, plasma clusterin concentrations were significantly higher in pwRRMS on fingolimod therapy compared to treatment-naïve pwRRMS and the control group. In addition, plasma clusterin concentration was increased in patients with rs11136000 & rs1532278 CC genotypes in the subgroup. These findings suggest that CLU SNPs and plasma clusterin concentrations could serve as significant biomarkers at different stages of MS.

To investigate the potential effects of systemic fingolimod treatment on parameters of the anterior segment of the eye and tear film function tests in patients with multiple sclerosis (MS). Forty-eight eyes of 24 individuals who were started on systemic fingolimod treatment for relapsing-remitting MS were prospectively enrolled in this study. Patients underwent examinations immediately before initiation of systemic fingolimod treatment, and at the first and sixth months of treatment. Anterior segment parameters were measured using Sirius Topography. The Schirmer-I test and tear break-up time (TBUT) were recorded during follow-up. Retinal thickness was also analyzed using spectral-domain optical coherence tomography (SD-OCT). There was no statistically significant difference in retinal thickness measurements between follow-up visits. The central corneal thickness, keratometric values, anterior chamber depth, aqueous humor depth, iridocorneal angle, horizontal anterior chamber tilt and anterior chamber volume values remained similar during follow-up. The Schirmer-I test value was 15.10 ± 2.65 mm at the zeroth month and 17.03 ± 3.61 mm at the sixth month (p = 0.044). The mean TBUT was significantly higher at the six-month visit compared to baseline and the one-month visit (p_0-6 < 0.001, p_1-6 < 0.001), but there was no statistically significant difference between baseline and month 1 (p_0-1 = 0.419). Systemic use of fingolimod may increase Schirmer I test and TBUT values in MS patients without altering other anterior segment parameters within 6 months.

This study aimed to assess the possible association between cognitive impairment and two important biochemical biomarkers of oxidative stress, thiol‐disulfide homeostasis (TDH), and ischemia‐modified albumin (IMA) in patients with multiple sclerosis (MS). This study included 85 patients with MS (38 treatment‐naïve relapsing–remitting MS (RRMS), 31 RRMS on fingolimod therapy, and 16 secondary progressive MS (SPMS)) and 33 healthy controls. Cognitive evaluation was carried out by applying the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) test battery and the scores were adjusted for age and years of education. Plasma TDH was assessed using an automated method and plasma IMA levels were determined using the cobalt‐albumin binding assay. Plasma native thiol and total thiol levels were significantly decreased in patients with SPMS when compared with the naïve patients and healthy controls. Cognitive impairment was detected in 47.4% of naïve patients, 64.5% of patients on fingolimod therapy, and 80% of patients with SPMS. Naïve patients or patients on fingolimod therapy who were cognitively impaired had significantly decreased levels of native thiol and total thiol compared to the cognitively normal patients. Logistic regression analysis revealed total thiol and native thiol to be significantly associated with cognitive impairment in naïve patients and patients on fingolimod therapy. Significant correlations were determined between BICAMS scores, TDH, IMA, clinical indices of disease severity (EDSS and MSSS), and magnetic resonance imaging parameters. This study has shown for the first time that plasma TDH parameters are associated with cognitive impairment in MS.