Multiple Sclerosis Patients Research Articles

Increased level of GATA3-AS1 long non-coding RNA is correlated with the upregulation of GATA3 and IL-4 genes in multiple sclerosis patients.

Long non-coding RNAs (lncRNAs) play various roles in gene regulation. GATA3 antisense RNA 1 (GATA3-AS1) is an lncRNA gene neighboring GATA binding protein 3 (GATA3). The current study aims to quantitatively compare the levels of the expression of GATA3-AS1, GATA3, and Interleukin-4 (IL-4) in peripheral blood mononuclear cells (PBMC) samples of MS patients and healthy individuals under the hypothesis of regulation of GATA3 and IL-4 expression orchestrated by GATA3-AS1. In this case-control study, the GATA3-AS1, GATA3 and IL-4 expression profiles were assessed using real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). Also, we assessed the IL-4 levels in the serum. The median fold changes in MS patients vs. controls were (4.39 ± 0.38 vs. 2.44 ± 0.20) for GATA3-AS1, (5.22 ± 0.51 vs. 2.86 ± 0.30) for GATA3, and (6.16 ± 0.52 vs. 3.57 ± 0.38) for IL-4, (P < 0.001). Furthermore, the mean serum levels of IL-4 were 30.85 ± 1.53 pg/ml in MS patients and 11.15 ± 4.23 pg/ml in healthy controls (P < 0.001). ROC curve analysis showed that the level of GATA3-AS1 might serve as a biomarker for diagnosing MS patients with the area under the curve (AUC = 0.918, P < 0.0001). Based on our results, this GATA3-AS1/GATA3/IL-4 pathway may increase IL-4 expression in MS patients. Our results indicate a probably regulatory function for GATA3-AS1and the levels of GATA3-AS1 in blood could be important biomarkers for MS diagnosis. To confirm and be more certain of these results, it is necessary to study neuromyelitis optica (NMO) and asthma patients in future studies.

The effect of education of self-care behaviors on the quality of life and resilience of multiple sclerosis patients

BackgroundMultiple sclerosis (MS) is one of the most common causes of non-traumatic disability in young adults. Typically, doctors diagnose MS between the ages of 20 and 50. This study aims to determine the effect of educational intervention on self-care behaviors on MS patients’ quality of life and resilience in Shiraz, Iran.MethodsThis interventional study included 90 individuals, aged 15 to 50, who were members of the support association for MS patients in Shiraz city, Iran. The study employed a convenient sampling method. Patients were randomly assigned to two experimental and control groups, and the self-care educational program was conducted during six educational sessions. The quality of life and resilience of the patients were measured before and after the study. Information was collected by completing the questionnaires before and three months after the intervention. To analyze the data, SPSS 23 was used. To describe the data, frequency, percentage, mean, and standard deviation indicators were used, and for analysis, independent t-tests and paired t-tests were used.ResultsThis study examined a total of 90 MS patients. 50.4% of the people in the study were married, 40% of them had a high school diploma, and 78.5% were unemployed. The results of the t-test showed that there was a significant difference between all the components of self-care, quality of life, and resilience before and after the intervention (P < 0.05).ConclusionBy accepting the responsibility of self-care, patients would improve the inadequacies and disabilities resulting from the disease, use the power of self-care to solve problems, and improve their quality of life and resilience.

Cognitive assessment in multiple sclerosis patients: electrophysiological and subjective studies

BackgroundMultiple sclerosis (MS) is a persistent inflammatory condition affecting the central nervous system, often associated with cognitive impairment. This impairment frequently presents itself as deficiencies in short-term memory, attention, and information processing speed. This research was designed to investigate P300 in patients with MS and its correlation with their cognitive function and their state of fatigue and depression. This work included two groups: the control group (20 subjects) and the study group (30 MS patients). Evaluation encompassed clinical history, audiological assessment, the Expanded Disability Status Scale (EDSS), the fatigue severity scale, the Beck Depression Inventory, Addenbrooke’s cognitive examination, and P300 component of event-related potentials (ERPs).ResultsThe study group exhibited varying degrees of fatigue and depression. The scores of Addenbrooke’s cognitive evaluation were reduced in the MS group. The MS group exhibited a considerably prolonged P300 latency compared to the control group.ConclusionThis study demonstrates the effectiveness of P300 in assessing cognitive function in persons diagnosed with MS.

The Characterization of the Th1/Th2 Ratio in Multiple Sclerosis Patients and its Response to a Dietary Supplement Regimen

Introduction Multiple sclerosis (MS) is a debilitating neurodegenerative disease affecting the central nervous system, causing disability and life-threatening complications. The interplay between immune cells and signaling pathways is a topic for investigating novel therapies. Past research has shown how the Th1/Th2 ratio plays a key role in the pathogenesis of MS lesions. Modulating the Th1/Th2 ratios with an efficacious dietary supplement may improve some of the consequences of MS. Methods Participants (n = 15) diagnosed with MS for an average of 12.4 years (standard deviation = 7.4; range = 2, 25) were enrolled in a clinical trial in which they consumed a dietary supplement regimen daily for 12 months. Venous blood was drawn at baseline and 12-month follow-up and peripheral blood mononuclear cells, cytokines, and growth factors were quantified. Infections, physical functioning, and quality of life were also assessed at baseline and 12 months. Results The IL-2/IL-10 and IFN-γ/IL-10 ratios were significantly higher than those of the healthy adults, and while only IFN-γ/IL-10 increased significantly at 12 months, all ratios other than IFN-γ/TNF-α increased over the course of the intervention. The decrease in yeast infections was inversely correlated with IL-2/TNF-α and IFN-γ/TNF-α. Significant improvements in physical functioning and quality of life correlated with changes in the Th1/Th2 ratios in response to the dietary supplement regimen. Conclusions The results show that dietary supplementation somewhat impacted the Th1/Th2 ratios over the course of the intervention (toward more Th1 dominance), and those changes were related to various clinical improvements of the participants’ symptoms in cognitive, motor, and psychosocial dimensions.

Non-contrast magnetic resonance evaluation of active multiple sclerosis lesions: Emerging role of quantitative synthetic magnetic resonance imaging.

The current study aims to explore the utility of novel synthetic MRI-derived quantitative parameters including myelin-correlated volume (MyC) in identifying active MS lesions without injecting gadolinium contrast. 43 MS patients underwent institutional MS protocol including 3D FLAIR and post-contrast 3D T1VIBE sequence on a 1.5T MR Scanner in addition to synthetic MRI sequence. MS plaques were categorised into enhancing (C) and non-enhancing (N) lesions. They were also sub-categorised based on location into periventricular WM lesions (P), deep WM lesions (D), infratentorial lesions (I) and cortical-juxtacortical (C) lesions. ROIs were placed on Synthetic FLAIR images in MS lesions and quantitative parameters of R1, R2, PD and myelin-correlated volume (MyC) obtained. Sensitivity and specificity for various cut-off values to differentiate enhancing from non-enhancing multiple sclerosis lesions were calculated by performing ROC curve analysis and logistic regression analysis. Contrast enhancing lesions demonstrated significantly higher mean R1, R2 values and lower mean PD values in comparison to non-enhancing lesions (p < 0.05) but with limited specificity. Region-wise analysis revealed high AUC values for mean R1 and R2 at cortical-juxtacortical lesions (p < 0.001) followed by periventricular lesions (p < 0.003) for differentiating enhancing from non-enhancing lesions with no significant contribution from MyC and PD values. Synthetic MRI-derived quantitative parameters of mean R1, R2, MyC and PD hold value in differentiating contrast enhancing and non-enhancing MS lesions without administering gadolinium-based contrast agent. However, the current study did not achieve significant specificity for establishing the same.

Disease-modifying therapies, outcomes, risk factors and severity of COVID-19 in multiple sclerosis: A MENACTRIMS registry based study

BackgroundThere is a lack information regarding risk factors associated with worse COVID-19 outcomes in patients with multiple sclerosis (MS) in the MENA region. MethodsThis is a multicenter, retrospective cohort study that included all MS patients with a suspected or confirmed COVID-19 infection using the MENACTRIMS registry. The association of demographics, disease characteristics, and use of disease-modifying therapies (DMTs) with outcomes and severity of COVID-19 were evaluated by multivariate logistic model. ResultsA total of 600 MS patients with confirmed (n = 542) or highly suspected (n = 58) COVID-19 were analyzed. Seventy-three patients (12.2 %) had a COVID-19 severity score of ≥3 on a 7-point ordinal scale (ranging from 1 [not hospitalized with no limitations on activities] to 7 [death] with a cutoff at 3 [hospitalized and not requiring supplemental oxygen]), and 15 patients (2.5 %) died. Out of 73 patients with a severity score ≥3, 90.4 % were on DMTs; 50.6 % of them were on anti-CD20, including ocrelizumab and rituximab. Multivariate logistic regression showed that older age (odds ratio per 10 years, 1.4 [95 %CI, 1.0–1.8]), disability (OR for EDSS 3.0–5.5, 2.9 [95 %CI. 1.5–5.7], OR for EDSS ≥6.0, 2.3 [95 %CI. 1.0–5.1]), obesity (OR, 3.0 [95 %CI, 1.5–6.0]), and treatment with rituximab (OR, 9.0 [95 %CI, 3.1–25.3]) or off-label immunosuppressive medications (OR, 5.6 [95 %CI. 1.1–27.8]) were risk factors for moderate or severe COVID-19. ConclusionIn this registry-based study of MS patients, age, sex, EDSS, obesity, progressive MS were risk factors for severe COVID-19. Moreover, there was an association found between exposure to anti-CD20 DMTs and COVID-19 severity.

Arm Swing Movements during Walking as an Early Predictor of Multiple Sclerosis Progression

Persons with Multiple Sclerosis (pwMS) are at a high risk of falling, with abnormal gait pattern. The upper limbs play an important role in postural control and gait stability. The presence of arm swing changes during walking in pwMS, especially in the early period, may be an indicator of balance problems. The current study aimed to assess arm swing during walking in early MS. A total of 18 pwMS were evaluated in two time points. The first time was after their first (stable) diagnosis (pre-evaluation) and the second time was 3 months after the pre-evaluation. In addition, 10 healthy controls were evaluated once. Arm swing analysis during walking, using video recording, was applied to both groups. Additionally, the MS group performed the Two-Minute Walk Test, Timed Up and Go, and Timed 25-Foot Walk Test. The pwMS showed similar joint angles at both the first and second evaluations. Only the elbow ROM value on the least affected side was lower in pwMS than healthy controls at the second evaluation (p = 0.027). The early MS patients showed altered arm swing pattern. As walking speed and mobility scores did not change over time, the decrease in elbow amplitude over a 3-month period indicates that the arm swing may present a pattern resulting from MS-specific disorders rather than being a compensatory mechanism in walking. From the earliest stages of the disease, variations in arm swing movements during walking may be considered as a disease progression-predictor for MS.

Analyzing the impact of pulse steroid therapy on relapse rates and disease progression in relapsing-remitting multiple sclerosis: a comprehensive retrospective study

Background and Objective: Relapsing remitting MS (RRMS) is characterized by recurrent relapses with remissions. Over an extended time-frame, high-dose steroid administration has primarily centered on the treatment of acute relapses, rather than relapse prevention. The objective of this retrospective study is to assess the long-term impact of administering three monthly pulse steroid therapy for three days on relapse rates and the Expanded Disability Status Scale (EDSS) scores in patients with RRMS. Methods: This study was conducted at Neurology ward of Chandka Medical College Hospital in Larkana from January 2021 to January 2023. A retrospective analysis of historical patient data, focusing on individuals with RRMS who received three monthly pulse steroid therapy over a specified period. Data was collected through patient records, including details of treatment, relapse history, and EDSS scores. Results: Thirty MS patients including 25 females and five males received one gram methylprednisolone intravenously every three months for three days. The mean age range was 18-50 years. Among them, three experienced no relapses, 11 had one relapse, 13 encountered two relapses, and three had three relapses over next consecutive two years. The severity of relapses varied, with 20 classified as moderate and seven as severe. A reduction in relapse rates and notable improvements in EDSS scores were observed. Conclusion: The initial findings from this retrospective analysis suggest that three monthly pulse steroid therapy is associated with positive outcomes in RRMS patients. These results support the need for further investigation into the potential benefits of continuous steroid therapy in managing RRMS.

Insight into motor fatigue mechanisms in natalizumab treated multiple sclerosis patients with wearing off

Motor fatigue in Multiple Sclerosis (MS) is due to reduced motor cortex (M1) output and altered sensorimotor network (SMN) modulation. Natalizumab, a disease-modifying therapy, reduces neuroinflammation and improves fatigue. However, some patients treated with natalizumab experience fatigue recurrence (‘wearing-off’) before subsequent infusions. Wearing-off provides a valuable window into MS-related motor fatigue mechanisms in a controlled, clinically stable, setting. This study investigates whether wearing-off is associated with worsening motor fatigue and its neurophysiological mechanisms and assesses natalizumab’s effect on MS-related fatigue. Forty-five relapsing–remitting MS patients with wearing-off symptoms were evaluated pre- and post-natalizumab infusion. Assessments included evaluating disability levels, depressive symptoms, and the impact of fatigue symptoms on cognitive, physical, and psychosocial functioning. The motor fatigue index was computed through the number of blocks completed during a fatiguing task and peripheral, central, and supraspinal fatigue (M1 output) were evaluated by measuring the superimposed twitches evoked by peripheral nerve and transcranial magnetic stimulation of M1. Transcranial magnetic stimulation-electroencephalography assessed M1 effective connectivity by measuring TMS-evoked potentials (TEPs) within the SMN before- and after the task. We found that wearing-off was associated with increased motor fatigue index, increased central and supraspinal fatigue, and diminished task-related modulation of TEPs compared to post-natalizumab infusion. Wearing-off was also associated with worsened fatigue impact and depression symptom scores. We conclude that the wearing-off phenomenon is associated with worsening motor fatigue due to altered M1 output and modulation of the SMN. Motor fatigue in MS may reflect reversible, inflammation-related changes in the SMN that natalizumab can modulate. Our findings apply primarily to MS patients receiving natalizumab, emphasizing the need for further research on other treatments with wearing-off.

Detection of diffusely abnormal white matter in multiple sclerosis on multiparametric brain MRI using semi-supervised deep learning

In addition to focal lesions, diffusely abnormal white matter (DAWM) is seen on brain MRI of multiple sclerosis (MS) patients and may represent early or distinct disease processes. The role of MRI-observed DAWM is understudied due to a lack of automated assessment methods. Supervised deep learning (DL) methods are highly capable in this domain, but require large sets of labeled data. To overcome this challenge, a DL-based network (DAWM-Net) was trained using semi-supervised learning on a limited set of labeled data for segmentation of DAWM, focal lesions, and normal-appearing brain tissues on multiparametric MRI. DAWM-Net segmentation performance was compared to a previous intensity thresholding-based method on an independent test set from expert consensus (N = 25). Segmentation overlap by Dice Similarity Coefficient (DSC) and Spearman correlation of DAWM volumes were assessed. DAWM-Net showed DSC > 0.93 for normal-appearing brain tissues and DSC > 0.81 for focal lesions. For DAWM-Net, the DAWM DSC was 0.49 ± 0.12 with a moderate volume correlation (ρ = 0.52, p < 0.01). The previous method showed lower DAWM DSC of 0.26 ± 0.08 and lacked a significant volume correlation (ρ = 0.23, p = 0.27). These results demonstrate the feasibility of DL-based DAWM auto-segmentation with semi-supervised learning. This tool may facilitate future investigation of the role of DAWM in MS.

Novel model of multiple sclerosis induced by EBV-like virus generates a unique B cell population

Epstein-Barr virus (EBV) is deemed a necessary, yet insufficient factor in the development of multiple sclerosis (MS). In this study, myelin basic protein-specific transgenic T cell receptor mice were infected with murid gammaherpesvirus 68 virus (MHV68), an EBV-like virus that infects mice, resulting in the onset neurological deficits at a significantly higher frequency than influenza or mock-infected mice. MHV68 infected mice exhibited signs including optic neuritis and ataxia which are frequently observed in MS patients but not in experimental autoimmune encephalomyelitis mice. MHV68-infected mice exhibited increased focal immune cell infiltration in the central nervous system. Single cell RNA sequencing identified the emergence of a population of B cells that express genes associated with antigen presentation and costimulation, indicating that gammaherpesvirus infection drives a distinct, pro-inflammatory transcriptional program in B cells that may promote autoreactive T cell responses in MS.

Telehealth Feasibility, Interest, and Satisfaction of Patients with Multiple Sclerosis Living in the Veneto Region, Italy, During the COVID-19 Pandemic.

Introduction: Synchronous telehealth (ST) consists of the remote real-time delivery of health services. COVID-19 pandemic has pressed the use of ST and forced neurologists to deliver telehealth services. The aim of this study was to obtain the actual picture of ST accessibility/interest and to evaluate the user satisfaction in patients with multiple sclerosis (MS) during the COVID-19 pandemic. Methods: The study consisted of two phases. First, a hard-copy questionnaire ("Telehealth Identity Card" [TIC]), including only yes/no questions, filled in the presence of a neurologist, and investigating the technical/practical access and the willingness/interest of MS patients to the telehealth services, was obtained from 600 consecutive outpatients, with no time limit for answering. Second, a fully filled "Televisit Satisfaction Questionnaire" (TSQ) was obtained from 100 consecutive patients that underwent a televisit. Statistical analysis applied the t test for normally distributed variables and the Mann-Whitney U test for ordinal. Logistic univariate and multivariate regressions were applied to predict televisit availability on the base of demographic variables. Results: Statistical analysis was performed on 552/600 consecutive TIC (92%). Of them, 464/552 (84%) of the MS patients declared to possess the tools and to be interested in telehealth services. Compared with noninterested patients, they were younger (mean age: 44.0 vs. 49.8, p < 0.001) and with lower disability (mean Expanded Disability Status Scale: 2.5 vs. 3.3, p < 0.01). From TSQ, it emerged that 95% agree or strongly agree that televisit respected timelines, saved time and money, was conducted with respect to privacy, can be a useful tool for monitoring disease and therapy, and expressed their availability for further televisits. Discussion: A great majority of MS patients living in Padua Province were interested in telehealth. High satisfaction and the willingness for further televist were expressed. Telehealth services can help neurologists to manage the increasing number of MS patients and their complex therapeutic monitoring.

The ageing central nervous system in multiple sclerosis: the imaging perspective.

The interaction between ageing and multiple sclerosis is complex and carries significant implications for patient care. Managing multiple sclerosis effectively requires an understanding of how ageing and multiple sclerosis impact brain structure and function. Ageing inherently induces brain changes, including reduced plasticity, diminished grey matter volume, and ischaemic lesion accumulation. When combined with multiple sclerosis pathology, these age-related alterations may worsen clinical disability. Ageing may also influence the response of multiple sclerosis patients to therapies and/or their side-effects, highlighting the importance of adjusted treatment considerations. Magnetic resonance MRI is highly sensitive to age- and multiple sclerosis-related processes. Accordingly, MRI can provide insights into the relationship between ageing and multiple sclerosis, enabling a better understanding of their pathophysiological interplay and informing treatment selection. This review summarizes current knowledge on the immuno-pathological and MRI aspects of ageing in the central nervous system in the context of multiple sclerosis. Starting from immunosenescence, ageing-related pathological mechanisms, and specific features like enlarged Virchow-Robin spaces, this review then explores clinical aspects, including late-onset multiple sclerosis, the influence of age on diagnostic criteria, and comorbidity effects on imaging features. The role of MRI in understanding neurodegeneration, iron dynamics, and myelin changes influenced by ageing and how MRI can contribute to defining treatment effects in ageing multiple sclerosis patients, are also discussed.

Beneficial therapeutic plasma exchange response in the treatment of severe relapses in patients with multiple sclerosis.

Therapeutic plasma exchange (PLEX) is effective as a second-line treatment of severe relapses of multiple sclerosis (MS) that failed to respond to standard steroid therapy. Our objective was to evaluate the effectiveness of PLEX in the severe MS relapses in a cohort of patients treated at Neurology Clinic, University Clinical Centre of Serbia, Belgrade, from 2007 until 2020. This retrospective study comprised 107 MS patients with 127 severe relapses treated with PLEX. Majority of our patients suffered from relapsing remitting MS (83.2%), 12.1% had secondary progressive MS and 4.7% had primary progressive MS. Mean age was 39.2 years (range, 19-79 years), female/male ratio 2.3:1. Pulse corticosteroid treatment was used before PLEX in 99.3% of patients. Median EDSS score at nadire during relapse was 6.0 (range 2.0-10.0). After PLEX, 73.8% relapses showed a marked clinical improvement, 7.1% showed mild improvement and in 19.0% there was no improvement. Median EDSS at discharge was 4.0 (6.0 at nadir of relapse vs. 4.0 at discharge; p<0.0001) and it was sustained at the same level, 6 month after PLEX. Multivariate regression analysis showed that higher EDSS at nadir during relapse (OR=0.63, 95% CI 0.41-0.96, p=0.039) and older age (OR=1.07, 95% CI 1.02- 1.12, p=0.010) were significantly associated with poor treatment response after 6- month follow-up. Adverse events occurred in 17.3 of procedures and they were completely resolved. Our study in a large cohort of MS patients confirmed that PLEX is effective.

Characterization of Japanese multiple sclerosis patients with progression independent of relapse activity: A 2-year multicenter cohort study

Progression independent of relapse activity (PIRA) is prevalent among Caucasian patients with relapsing and remitting multiple sclerosis (RRMS). However, there is limited knowledge regarding the characteristics of PIRA in Asian patients with RRMS. Therefore, we retrospectively analyzed the clinical and radiological progression of 95 Japanese patients with RRMS during a 2-year observation period. PIRA was observed in three patients who were characterized by young age, large T2 lesion volume, and great reduction in brain volume. Despite having highly active disease, fewer patients with PIRA (33.3%) were treated with high-efficacy drugs compared with those without disease activity (60.7%).

Inhomogeneous magnetization transfer (ihMT) imaging reveals variable recovery profiles of active MS lesions according to size and localization

Abstract This work aims at exploiting the unique myelin specificity of the inhomogeneous magnetization transfer (ihMT) technique to characterize the recovery dynamics of active multiple sclerosis (MS) lesions. IhMT and three other myelin-sensitive techniques, conventional MT, T1-weighted, and diffusion tensor imaging, were applied in a 12-month longitudinal study performed on relapsing-remitting MS patients. An exponential recovery model was used to fit the variations over time of the metrics derived from each MR technique within new active lesions. A principal component analysis was performed on the model parameters obtained for all MR myelin-sensitive techniques across all active lesions of all patients to identify specific recovery profiles. The results show that the recovery profiles of myelin-sensitive MR metrics in active MS lesions vary according to the localization and size of lesions. The distance of lesions from the ventricles is positively associated with the recovery rates of ihMTR and T1w-MPRAGE: the further the lesion is from the ventricles, the higher the recovery rate of these metrics. Lesion size is positively associated with initial loss and negatively associated with final recovery of ihMTR and other MR metrics: small lesions have lower initial loss and greater final recovery of MR metrics than large lesions. Thanks to the specificity of the ihMT technique for myelin, these features can be interpreted in terms of remyelination. This study thus provides longitudinal in vivo support for the pathological observations of higher remyelination in small lesions compared with large ones and faster remyelination in lesions away from the ventricles. These results support the use of ihMT and other measures for quantifying remyelination rates in clinical studies of remyelination therapies.

Association of Clinical Relapses With Disease Outcomes in Multiple Sclerosis Patients Older Than 50 Years.

Relapse and MRI activity usually decline with aging but are replaced by progression independent of relapse activity (PIRA) in patients with multiple sclerosis (PwMS). However, several older PwMS continue to experience clinical relapses, and the impact on their disease remains undetermined. We aimed to determine the impact of an index relapse on disease outcomes in patients older than 50 years and to identify risk factors of disadvantageous outcomes. We performed a secondary analysis from 3 prospective cohorts in Germany. We evaluated all PwMS 50 years and older with a relapse ≤60 days before a baseline visit and at least 18 months of follow-up compared with a control cohort of PwMS without a relapse. Patients were stratified according to age ("50-54" vs "55-59" vs "60+") or disease outcomes ("stable" vs "active" vs "progressive," according to the Lublin criteria). We analyzed relapses, MRI activity, relapse-associated worsening, and PIRA. Regression analysis was performed to evaluate the association of specific baseline risk factors and treatment regimen changes with disease outcomes at month 18. A total of 681 patients were included in the "relapse cohort" (50+: 361; 55+: 220; 60+: 100). The "control cohort" comprised 232 patients (50+: 117; 55+: 71; 60+: 44). Baseline epidemiologic parameters were balanced among cohorts and subgroups. We observed increased abundance of inflammatory activity and relapse-independent disability progression in the "relapse" vs "control" cohort. In the "relapse" cohort, we identified 273 patients as "stable" (59.7%), 114 patients as "active" (24.9%), and 70 patients as "progressive" (15.3%) during follow-up. Cardiovascular risk factors (CVRFs) and older age at baseline were identified as risk factors of progressive, whereas disease-modifying treatment (DMT) administration at baseline favored stable disease. DMT during follow-up was associated with stable over active, but not over progressive disease. A relapse-suggesting underlying active disease-in PwMS older than 50 years was associated with continued disease activity and increased risk of PIRA. Presence of CVRF and absence of DMT at baseline appeared as risk factors of disadvantageous disease courses. An escalation of DMT switch was associated with stable over active but not progressive disease.

Methylation of Interleukin-1 receptor-associated kinase-3 and the risk of multiple sclerosis relapse/activity

This study retrospectively investigated the impact of interleukin-1 receptor-associated kinase-3 (IRAK-3/IRAK-M) silencing by methylation on the likelihood of multiple sclerosis (MS) activity. This cross-sectional study included 90 patients with MS: 45 with active disease (Group 1), 45 in remission (Group 2), and 45 healthy controls. The study included quantitation of IRAK-3 methylation index (MI%), IRAK-3 mRNA, and myeloid differentiation factor88 (MyD88) and assessment of NF-κB activity.IRAK-3 MI% was significantly higher in group 1 compared to group 2, accompanied by lower IRAK-3 mRNA expression, elevated circulating MyD88, and increased NF-κB activity. IRAK-3 MI% correlated negatively with its transcript and positively with MyD88 and NF-κB activity. A logistic regression model was created to predict active demyelination. The C-index was 0.924, which indicates a very strong prediction model. Within the limitations of current work, IRAK-3 methylation level seems to be a promising candidate biomarker for identifying MS patients at risk of relapse.

Association of Autoimmune Diseases with the Risk of Parkinson's Disease.

PD is a progressive neurodegeneration disease characterized by cardinal motor symptoms such as bradykinesia and tremor. The pathogenesis of PD remains unclear. It is hypothesized that immune system dysfunction may contribute to PD. Thus, autoimmune diseases may influence the risk of incident PD. We included 398,329 participants without PD at the baseline from UK Biobank. The association between 20 autoimmune diseases with PD was examined using cox hazards regression analyses, adjusting covariates like age, sex, and smoking status in the statistical models. Sensitivity analyses were conducted, adjusting for polygenic risk score and the reported source of PD, to check the robustness. After an average follow-up of 13.1 ± 0.816 years, 2,245 participants were diagnosed with incident PD. After multiple comparison correction, only multiple sclerosis (MS) reached statistical significance and showed an increased risk for incident PD. Compared with non-MS patients, the risk of incident PD in MS patients was 2.57-fold with age and sex being adjusted (95% CI, 1.59-4.14; adjust p value = 0.002). After adjusting lifestyle and other factors, the hazard ratio of incident PD in MS patients was 2.49 (95% CI, 1.55-4.02; adjust p value = 0.004). Excluding the self-reported PD cases in the sensitivity analysis, MS was a detrimental factor for incident PD (HR, 2.06; 95% CI, 1.56-4.05; adjust p value = 0.004). The link between MS and PD did not reach the statistical significance in the sensitivity analysis adjusting the PRS (adjust p value = 0.95). Our study provided evidence from observational analyses that MS was associated with an increased risk of PD. Further investigations should be performed to determine the causal association and potential pathophysiology between MS and PD.

Medicinal plants used in multiple sclerosis patients, prevalence and associated factors: a descriptive cross-sectional study

IntroductionMultiple sclerosis (MS) is a chronic and debilitating disease that not only leads to disability and associated condition but also impacts one’s ability to maintain a professional life. People’s acceptance and utilization of medicinal plants (MPs) play an important role in managing their treatment process. As a result, this study aims to investigate the use of medicinal herbs among patients with MS.MethodsA descriptive cross-sectional study was conducted on 150 MS patients who visited a private clinic and the MS Association in Kerman, Iran in 2021. A questionnaire comprising questions about sociodemographic information, disease variables, and aspects of MPs usage was utilized for data collection. Statistical analysis was performed using SPSS version 20 (SPSS Inc., Chicago, IL). The Chi-square test was employed to identify any association between demographic characteristics and MPs usage. To determine the prevalence of plant use in a specific area and the consensus among informants, the use value (UV) and Informant consensus factor (Fic) were calculated.ResultsThe study revealed a high prevalence of MPs usage among MS patients. Chamomile (66.6%) and golegavzaban (62.0%) were the most commonly used plants with the highest UV indices (0.88 and 0.82 respectively), while St. John’s wort and licorice were rarely used (0.67% and 4% respectively). Participants cited pursuing a healthier lifestyle as the primary reason for using MPs (24%). St. John’s wort, lavender, and chamomile were the most satisfying plants (100%, 100%, and 53.0% respectively). Chamomile had the highest Fic too. Most patients were motivated to get MPs from their relatives.ConclusionsGiven the widespread use of MPs among MS patients, neurologists should enhance their knowledge in this area to guide patients away from seeking advice from non-professionals. Providing standardized formulations can help prevent potential interactions between MPs and mainstream drugs, thereby improving patients safety and outcomes.