Multiple Sclerosis Foundation

The Paced Auditory Serial Addition Test (PASAT) is widely used to assess cognitive functioning and fatigability in people with Multiple Sclerosis (PwMS). However, its poor acceptability and high refusal rates may limit its clinical interpretability, while potentially conveying meaningful information beyond test performance. To determine whether PASAT rejection at the first assessment represents a clinically meaningful marker of overall vulnerability in PwMS, reflected by a tendency toward worsening across demographic, disease-related and clinical domains, using both patient-reported and clinician-assessed outcomes. One-way ANOVAs or non-parametric equivalents were run to compare different groups defined by baseline PASAT performance (missing, low, high) in terms of demographic, disease-related and clinical variables. Retrospective data from 1154 PwMS were analyzed. Participants with missing PASAT (N=224) were significantly older (60.1±13.5 years), had longer disease duration (18.9±12.2 years), higher EDSS (6.1±2.0), lower educational level (9.9±3.9 years), poorer cognitive performances on the Montreal Cognitive Assessment (MoCA) and Symbol Digit Modalities Test (SDMT) (respectively, 17.4±6.5, 22.5±13.6), and higher level of required assistance in daily functioning as measured by the Functional Independence Measure (FIM) (91.1±29.3), compared with both low and high PASAT groups (all ps < 0.05). PASAT rejection at first assessment identifies a subgroup of older PwMS with higher disability, lower education, and more pronounced cognitive and functional impairments, suggesting that test refusal may serve as a clinically relevant marker of overall vulnerability in MS.

Background:Disability accrual in multiple sclerosis (MS) is highly variable and challenging to predict, complicating personalised care. Integrating machine learning (ML) with patient-reported outcomes (PROs) and clinician-assessed outcomes (CAOs) may support tailored interventions.Objectives:To develop and validate an interpretable ML model for predicting disability accrual trajectories in MS.Methods:A multicentre data set of 1,176 MS patients with up to 8 years of follow-up was used. A random forest model was trained to predict disability accrual at 2, 3, 4, and 5 years, using baseline clinical variables, PROs and initial risk class as predictors. Model performance was assessed using accuracy, area under the curve, and survival analysis.Results:437 patients composed final cohort. The model predicted disability changes with an accuracy of 0.82 (95% CI: 0.77–0.86) at 2 years and 0.73 (95% CI: 0.66–0.80) at 5 years. Initial risk class and baseline Expanded Disability Status Scale (EDSS) were the most influential predictors. Survival analysis confirmed model’s ability to effectively capture the time-dependent patterns of disability accrual events at the population level (log rank p > .05).Conclusions:The model offers robust and interpretable predictions that may support clinical decision-making using routine clinical data.

For a comprehensive study of such a socially significant disease as multiple sclerosis (MS), which occurs predominantly in people of working age and in which neuroinflammation and neurodegeneration go hand in hand, resulting in irreversible damage to the brain and spinal cord, the key point is to decipher the pathophysiological mechanisms of its development and progression. Despite the established relationship between hyperhomocysteinemia and secondary endothelial damage, data on the possible role of homocysteine (Hcy) in disease progression are quite contradictory.Objective: to investigate the informative value of determining the content of markers of oxidative stress, mitochondrial and endothelial dysfunction in patients with MS.Material and methods. The study included 63 patients with MS (40 women, 23 men) aged 35 [30; 43] years. The control group consisted of 43 healthy volunteers (22 men, 21 women) aged 37 [32; 44] years. Depending on the therapy received, patients were divided into two groups: those receiving first-line and second-line therapy; patients receiving natalizumab therapy were considered separately. A neurological examination of patients was performed with an assessment of disease severity using the EDSS scale, and the disease progression index was calculated. The following biomarkers were also determined in the blood of patients and volunteers using enzyme-linked immunosorbent assay: intercellular adhesion molecules (ICAM-1), S-adenosylmethionine, S-adenosylhomocysteine, cysteine, cysteinylglycine, glutathione, and Hcy.Results. A statistically significant correlation was found between disease severity (EDSS disability level) and increased Hcy levels. A statistically significant increase in ICAM-1 levels was also found in patients during periods of disease activity (clinical exacerbation, activity according to MRI data), which allows this molecule to be considered as a biomarker of endothelial dysfunction and inflammation.Conclusion. The results of the study indicate the need to continue studying the pathophysiological causes of the onset and progression of MS, further identifying new biomarkers for predicting the course of MS, and evaluating the effectiveness of drugs that alter the course of MS.

Introduction. The study was driven by the prevalence of secondary progressive multiple sclerosis (SPMS) in Russia and the lack of data on siponimod in the real clinical practice (RCP).Aim. To collect and analyze data on the administration of siponimod in SPMS patients within Russia’s RCP as part of the EMBOSSES study (rEtrospective Multicenter oBservatiOnal Study Siponimod rEal-world Spms).Materials and methods. The study encompassed data of 606 SPMS patients from 11 centers who received siponimod for at least 6 months. The analysed data included demographic and clinical characteristics of patients, changes in the Expanded Disability Status Scale (EDSS) scores over time, percentage of patients with 6-month confirmed disability progression (6mCDP), annualized relapse rate (ARR) for MS, radiological signs of the disease activity and adverse events (AEs).Results. Among the study patients, women predominated (64.9%), while men accounted for 35.1%. The median age of patients was 49.5 (±8.9) years. 143 (23.6%) patients reported relapses during 2 years, whereas relapse-free SPMS was observed in 463 (76.4%) patients. The average EDSS scores remained stable, demonstrating minimal changes from 5.44 (±0.998) to 5.58 (±1.028) scores during the 2-year therapy. The percentage of patients free from 6mCDP was 85.5%. The KaplanMeier analysis revealed that 25% of patients achieved 6mCDP by Month 27 of therapy. The average ARR decreased from 0.14 to 0.032 at 12 months and remained low (0.062) after 2 years of treatment. The MRI showed a decrease in the percentage of patients with Gd+ T1 lesions to their complete absence over 2 years of therapy. Main AEs: lymphopenia, bradycardia, and elevated liver enzymes; serious AEs were observed in 3.3% of all cases.Conclusions. Siponimod demonstrated efficacy in controlling disability progression and inflammatory activity, as well as a favourable safety profile in patients with SPMS in the RCP setting. The results confirm the feasibility of using siponimod in patients with SPMS.

Smart environments can play a crucial role in providing personalized assessment protocols for individuals. This study proposes a wearable telemonitoring system for noninvasively collecting and tracking mobility and mental effort parameters. The system consists of sensorized glasses, insoles, and AI algorithms for evaluating key metrics. To extract data, the activity "preparing coffee for two people" was performed by healthy participants. Preliminary results indicate that, on average, participants completed the task in 8 minutes. Mental workload, assessed through pupil diameter, showed a mean pupil diameter of $\mu=5.19 ~\text{mm}$ with a standard deviation of $\sigma=0.99 ~\text{mm}$. On average, participants took 340 steps during the task. Questionnaire responses demonstrated good system usability. The findings provide insights into user perceptions of the monitoring approach and highlight the system's potential for clinical adoption.

To evaluate the immunological safety profile of prolonged UBL treatment.

Disease-modifying therapies (DMTs) are vital for managing multiple sclerosis (MS), but research using administrative data often excludes patient preferences and factors clinicians consider in treatment decisions. Patient experience data are crucial to understand and improve MS treatment initiation, adherence, and outcomes. A cross-sectional survey of US adults with MS or clinically isolated syndrome was conducted online from December 2022 to January 2023 by the MS Coalition. A mixed methods analysis was conducted: logistic regression for quantitative data and thematic analysis of qualitative data. Among 1,323 participants (median age 55; 78% female), 80% expressed concerns about loss of independence, 65% about financial impacts, 64% about emotional impacts, 57% about relationships, and 42% about careers. Emotional tolls included identity loss, stress from navigating healthcare, and financial strain on families. Concerns varied by age, sex, and disability status. Nearly all participants (97%) reported DMT experience, with 73% having used two or more DMTs. Key factors in initiating DMT included slowing disease progression (92%), preventing relapses (89%), and following medical advice (89%). Financial barriers, such as high out-of-pocket costs, led to treatment delays or discontinuation in 19%. Barriers varied by demographic factors and included stress from medication costs, insurance denials, and fear of losing health coverage. Financial assistance was crucial for many. Half of participants had stopped a DMT due to doctor recommendations, side effects, or insurance issues. The survey highlights the emotional and financial burdens of living with MS, including concerns about independence and relationships. The findings underscore the need for comprehensive care and provide actionable recommendations for managed care, research, and healthcare providers.

Using the case study of the Multiple Sclerosis Care Unit Initiative launched by the European Charcot Foundation, we discuss the need to evaluate the impact of multidisciplinary and multi-stakeholder healthcare systems on patient-reported experience and outcomes for the programming and monitoring of brain and neurodegenerative diseases in Europe and beyond. The multiple sclerosis (MS) case study presented in this paper highlights the role of patient-generated data as indicators of the impact of value-based healthcare (VBHC) for all the different neurological diseases whose prodromal symptoms are the first signs of disease progression and therefore instrumental markers for preventive treatments to preserve brain health. A holistic approach to the treatment of MS plays a crucial role in the inclusion and scientific meaning of the patient’s perspective in terms of patient-reported dimension and patient-generated health data (PGHD).

Multiple sclerosis (MS)-related disability in Hispanic people with MS is associated with inequities in social determinants of health (SDOH) as measured by composite indices of areal-level census data. Studies of individual-level measures of SDOH are lacking. This study examined the separate and joint effects of person-centered SDOH indicators and an area-level composite on MS disability measures. Hispanic people diagnosed with MS (≤5 years) who had SDOH and Social Deprivation Index (SDI) based on 2015-2019 American Community Survey estimates were included. At study entry, data on MS disability outcomes were collected: Expanded Disability Status Scale (EDSS) score, Symbol Digit Modality Test (SDMT) score, Hauser Ambulation Index (HA index), and 25-Foot Walk Time (25FWT). Principal component analysis was used to identify person-centered SDOH factors, mapped across a socioecological model. Multivariable regression modeling measured separate and joint effects of SDOH principal components (PCs) and SDI on outcome measures. Of the 170 participants with MS, most were women (71.9%) and had a mean age at first symptom of 34.01 (SD ±11.24) years and at diagnosis of 36.27 (SD ±10.68) years. The top 2 PCs were identified to represent person-centered SDOH related to assimilation and socioeconomic disadvantage in multivariable models. In both separate and joint effect models, both PC1 and PC2 were significantly associated with longer 25FWT (β 0.43, 95% CI 0.04-0.82, and β 0.66, 95% CI 0.28-1.05), higher HA index (β 0.22, 95% CI 0.04-0.41, and β 0.31, 95% CI 0.12-0.51), and higher EDSS score (β 0.39, 95% CI 0.16-0.62, and β 0.36, 95% CI 0.13-0.60). PC1 was also significantly associated with a lower SDMT score (β -4.15, 95% CI -5.60 to -2.69). SDI was significantly associated with lower SDMT score and higher HA index in separate effect models but was not associated with any outcome measure in joint effect models with PCs. Our findings suggest that census-based indicators may underestimate the effect of SDOH on MS outcomes and the person-centered level measures are better markers of disease severity in Hispanic people with MS. Future research and policy change can focus on the amelioration of assimilation barriers and socioeconomic disadvantage because these were strongly associated with MS-related ambulatory and cognitive disability.

नेपाली साहित्यका एक उज्ज्वल नक्षत्र कवि माधवप्रसाद घिमिरेले नेपाली साहित्यमा अतुलनीय योगदान दिएका छन् । आफ्ना रचनामार्फत् मानवता, राष्ट्र प्रेम अनि प्रकृति प्रेमको चित्रण गर्ने घिमिरेले राजेश्वरी खण्डकाव्यमा पनि मानवतालाई नै प्रमुख केन्द्र बनाएका छन् । ऐतिहासिक विषयवस्तुमा आधारित राजेश्वरी खण्डकाव्यमा प्राकृतिक सुन्दरता, राष्ट्रप्रेम,दरवारिया छलछाम, मानवता प्रस्तुत गरिएको छ । शासन सत्ताका लागि हुने षड्यन्त्र, मानवमा हराउँदै गएको मानवता, छलछाम राजेश्वरी खण्डकाव्यमा प्रस्तुत गरिएको छ । दरवाररियाको षड्यन्त्रले एक्लै हेलम्बुमा निर्वासित जीवन बिताइरहेकी रानी राजेश्वरीलाई दूतहरूले राजाको झुटो प्रेम सन्देश सुनाएर सती जानका निम्ति त्यहाँबाट ल्याइन्छ । रानी राजेश्वरीलाई छल गरेर दूतहरुले एक वास वर आएर मात्र राजा स्वर्गे भएको खबर सुनाउँछन् । रानीले त्यो वासस्थान नै आफ्नालागि उचित भएको, आफूलाई मान्छेको दुर्गन्धदेखि टाढा बस्न मन लाग्ने, त्यस पर्णकुटीमा मैले आफ्नो जीवन आनन्दले बिताएकी छु मलाई हेलम्बुमै फर्कन देऊ भनी आग्रह गर्छिन् तर उनलाई फर्किन दिइदैन । राजा स्वर्गे भएको खबरले दुखी बनेकी रानीका पीडाको प्रस्तुति पाँचौँ छालमा गरिएको छ । पतिको जीवन रहुन्जेल मात्र पत्नीको जीवन छ, श्रृङ्गार छ, सुख छ ,जीवन सार्थक छ । राजाको अवसान पछि रानीले आफ्नो श्रृङ्गार धुनु पर्ने, जीवन दुःखैदुःखले भरिने, क्षणभरमै जीवन ओइलिने, वैधव्यको जीवन जिउनु पर्ने जस्ता मर्मस्पर्शी भाव पाँचौँ छालमा व्यक्त गरिएको छ । रानीलाई छल गरेर दूतहरूले हेलम्बुबाट ल्याएका हुन्छन् । राजाको मृत्युको खबरले रानीका मनमा आएका पीडाभावका साथै मलाई हेलम्बुमै फर्कन देऊ म त्यही एकान्तमा गएर आफ्नो शेष जीवन तपस्वी बनेर बिताउने छु भन्ने भाव पाँचौँ छालमा व्यक्त गरिएको छ ।