Multiple Sclerosis Research Articles

Spatial transcriptomics of meningeal inflammation reveals inflammatory gene signatures in adjacent brain parenchyma.

While modern high efficacy disease modifying therapies have revolutionized the treatment of relapsing-remitting multiple sclerosis, they are less effective at controlling progressive forms of the disease. Meningeal inflammation is a recognized risk factor for cortical gray matter pathology which can result in disabling symptoms such as cognitive impairment and depression, but the mechanisms linking meningeal inflammation and gray matter pathology remain unclear. Here, we performed magnetic resonance imaging (MRI)-guided spatial transcriptomics in a mouse model of autoimmune meningeal inflammation to characterize the transcriptional signature in areas of meningeal inflammation and the underlying brain parenchyma. We found broadly increased activity of inflammatory signaling pathways at sites of meningeal inflammation, but only a subset of these pathways active in the adjacent brain parenchyma. Subclustering of regions adjacent to meningeal inflammation revealed the subset of immune programs induced in brain parenchyma, notably complement signaling and antigen processing/presentation. Trajectory gene and gene set modeling analysis confirmed variable penetration of immune signatures originating from meningeal inflammation into the adjacent brain tissue. This work contributes a valuable data resource to the field, provides the first detailed spatial transcriptomic characterization in a model of meningeal inflammation, and highlights several candidate pathways in the pathogenesis of gray matter pathology.

Spatial transcriptomics of meningeal inflammation reveals inflammatory gene signatures in adjacent brain parenchyma

While modern high efficacy disease modifying therapies have revolutionized the treatment of relapsing-remitting multiple sclerosis, they are less effective at controlling progressive forms of the disease. Meningeal inflammation is a recognized risk factor for cortical gray matter pathology which can result in disabling symptoms such as cognitive impairment and depression, but the mechanisms linking meningeal inflammation and gray matter pathology remain unclear. Here, we performed magnetic resonance imaging (MRI)-guided spatial transcriptomics in a mouse model of autoimmune meningeal inflammation to characterize the transcriptional signature in areas of meningeal inflammation and the underlying brain parenchyma. We found broadly increased activity of inflammatory signaling pathways at sites of meningeal inflammation, but only a subset of these pathways active in the adjacent brain parenchyma. Subclustering of regions adjacent to meningeal inflammation revealed the subset of immune programs induced in brain parenchyma, notably complement signaling and antigen processing/presentation. Trajectory gene and gene set modeling analysis confirmed variable penetration of immune signatures originating from meningeal inflammation into the adjacent brain tissue. This work contributes a valuable data resource to the field, provides the first detailed spatial transcriptomic characterization in a model of meningeal inflammation, and highlights several candidate pathways in the pathogenesis of gray matter pathology.

Prediction Intervals for Overdispersed Poisson Data and Their Application in Medical and Pre-Clinical Quality Control.

In pre-clinical and medical quality control, it is of interest to assess the stability of the process under monitoring or to validate a current observation using historical control data. Classically, this is done by the application of historical control limits (HCL) graphically displayed in control charts. In many applications, HCL are applied to count data, for example, the number of revertant colonies (Ames assay) or the number of relapses per multiple sclerosis patient. Count data may be overdispersed, can be heavily right-skewed and clusters may differ in cluster size or other baseline quantities (e.g., number of petri dishes per control group or different length of monitoring times per patient). Based on the quasi-Poisson assumption or the negative-binomial distribution, we propose prediction intervals for overdispersed count data to be used as HCL. Variable baseline quantities are accounted for by offsets. Furthermore, we provide a bootstrap calibration algorithm that accounts for the skewed distribution and achieves equal tail probabilities. Comprehensive Monte-Carlo simulations assessing the coverage probabilities of eight different methods for HCL calculation reveal, that the bootstrap calibrated prediction intervals control the type-1-error best. Heuristics traditionally used in control charts (e.g., the limits in Shewhart c- or u-charts or the mean ± 2 SD) fail to control a pre-specified coverage probability. The application of HCL is demonstrated based on data from the Ames assay and for numbers of relapses of multiple sclerosis patients. The proposed prediction intervals and the algorithm for bootstrap calibration are publicly available via the R package predint.

Clinical and Epidemiological Study of Multiple Sclerosis in Svoge and Troyan

Multiple sclerosis is a chronic inflammatory, autoimmune, demyelinating and neurodegenerative disease of the central nervous system. It is characterized by various symptoms depending on the area affected – brain, spinal cord or optic nerves. Multiple sclerosis typically presents at age 20–40 years and affects women more often than men. It is the most frequent nontraumatic disease causing neurologic deficit among young people. According to the 3rd edition of Atlas of MS, published by The Multiple Sclerosis International Federation in 2020, there are 2.8 million people living with the disease around the world. The last study on the epidemiology of multiple sclerosis in Bulgaria was published in 1999. It estimated prevalence of 44.5/100 000 and incidence 1.03/100 000. We present an epidemiological study conducted between January 2016 and December 2020 in two small areas in Bulgaria with homogenous and stable population – Svoge and Troyan. The estimated prevalence of multiple sclerosis in Troyan was 116.5/100 000 with incidence of 28.2/100 000. The prevalence and incidence of multiple sclerosis in Svoge were 117.7/100 000 and 24.5/100 000, respectively. The reason for the higher prevalence and incidence rates in our study may be explained by the better diagnosis of the disease according to well defined diagnostic criteria, the longer survival of the affected individuals and the availability of various disease modifying therapies.

Guideline-recommended standardized instruments in multiple sclerosis : Acomparative content analysis based on the International Classification of Functioning, Disability and Health (ICF)

Guidelines serve as practice-based decision support and recommend the use of standardized instruments to measure functional capacity in individuals with multiple sclerosis (MS). However, the extent to which aperson's functioning is captured by these instruments is unclear. The aim of this study is to link the content of the MS disease guideline with the International Classification of Functioning, Disability and Health (ICF) in order to capture the distribution of the content on the functional domains and contextual factors and to uncover existing gaps. Instruments of the S2k guideline "Diagnosis and therapy of multiple sclerosis, neuromyelitis optica spectrum diseases and MOG-IgG-associated diseases", which were available free of charge in German or English and designed for adult people, were included. The instruments were classified into their meaningful concepts (meaningful concepts = MCs) and subsequently coded using standardized ICF rules by two raters. The 23 included instruments contained 351 items and 718 MCs. Of these, 663 MCs could be linked to the ICF according to the coding rules. Of these, 51% (340 MCs) related to body functions, 44% (291 MCs) to the activity and participation component, and 5% (32MCs) to environmental factors. The most frequently coded chapter was mobility (d4) with 201 MCs. Interrater agreement was k = 0.79. The linking of the guideline-recommended instruments to the ICF shows that the instruments cover different themes. The area of environmental factors is underrepresented. The ICF linkage reveals abroad spectrum of functioning covered by the guideline-recommended instruments and facilitates the selection of appropriate instruments for the affected persons.

Engaging wheelchair and scooter users in the co-design of an mHealth application for fall prevention and management: thematic analysis of focus group research

This study aimed to explore the potential of a mobile health (mHealth) application (app) to support the delivery of a fall prevention and management program, Individualized Reduction of FaLLs (iROLL), for people with spinal cord injury (SCI) and multiple sclerosis (MS) who use wheelchairs and scooters (WC/S) full-time by seeking end-users’ input into the functioning and ongoing design of the iROLL-O + mobile app. Two focus group discussions included nine adults with SCI or MS who used a WC/S for at least 75% of mobility, who experienced at least one fall in the past three years and have internet and access to an internet-capable device. One group had prior iROLL experience (n = 4); while the other had none (n = 5). The focus groups examined the app’s usefulness, accessibility, appearance, and ease of use. The participants with prior iROLL experience also discussed how the app would enhance their experience with the program. Thematic analysis revealed five app-related themes: perceived usefulness, perceived usability, accessibility, appearance, and enhancement of the iROLL experience, with participants providing actionable suggestions for improvement. Participants with previous exposure to the iROLL program emphasized the app’s potential to facilitate flexible access to the program and expand its reach to a wider audience. The iROLL-O + app was perceived positively, especially with respect to the enhancement of users’ access and experience with the program. Focus group findings will inform ongoing app development for optimized usability and reduced likelihood of technology abandonment. IMPLICATIONS FOR REHABILITATION End-users’ impressions of the Individual Reduction of faLLs Online application (iROLL-O + app) highlight the potential for integrating mHealth apps in fall prevention and management education efforts, offering a promising and accessible avenue to support the delivery of tailored programs. The study notes that the app facilitates flexible access and wider reach to the program, indicating the importance of incorporating features that enhance accessibility and accommodate the diverse needs of individuals who use wheelchairs and scooters. Actionable suggestions provided by participants underscore the importance of a user-centered design approach in developing rehabilitation-related mobile apps.

Toxoplasmosis infection in an HIV-negative patient presenting with clinical and MRI findings similar to those of multiple sclerosis

Toxoplasmosis is a parasitic infection that can present in various clinical forms, ranging from asymptomatic to severe neurological manifestations. The primary sources of infection include undercooked meat, unwashed produce and contact with cat faeces. Toxoplasmosis can lead to encephalitis, particularly in immunocompromised patients, and is often misdiagnosed as other neurological conditions such as multiple sclerosis (MS). We report the case of a 44-year-old male from Almaty, Kazakhstan, who presented with neurological symptoms including headaches, dizziness, diplopia, leg weakness and elevated blood pressure. The patient had a history of consuming undercooked meat, but no prior neurological conditions. Initial magnetic resonance imaging (MRI) revealed demyelinating lesions, leading to a diagnosis of MS. However, high levels of IgG antibodies against Toxoplasma gondii were detected, prompting further testing. A polymerase chain reaction test for toxoplasmosis was negative, but the patient was treated empirically with trimethoprim and sulfamethoxazole for six months. A follow-up MRI showed a significant reduction in brain lesions, and the patient’s symptoms improved.

The impact of high dose corticosteroid treatment affect on cardiac abnormalities in patients with multiple sclerosis

The impact of high dose corticosteroid treatment affect on cardiac abnormalities in patients with multiple sclerosis

The role of inflammation in neurological disorders: a brief overview of multiple sclerosis, Alzheimer’s, and Parkinson’s disease’

Neuroinflammation is a central feature in the pathophysiology of several neurodegenerative diseases, including MS, AD, and PD. This review aims to synthesize current research on the role of inflammation in these conditions, emphasizing the potential of inflammatory biomarkers for diagnosis and treatment. We highlight recent findings on the mechanisms of neuroinflammation, the utility of biomarkers in disease differentiation, and the implications for therapeutic strategies. Advances in understanding inflammatory pathways offer promising avenues for developing targeted interventions to improve patient outcomes. Future research should focus on validating these biomarkers in larger cohorts and integrating them into clinical practice to enhance diagnostic accuracy and therapeutic efficacy.

Spatial structural abnormality maps associated with cognitive and physical performance in relapsing-remitting multiple sclerosis.

We aimed to characterize the brain abnormalities that are associated with the cognitive and physical performance of patients with relapsing-remitting multiple sclerosis (RRMS) using a deep learning algorithm. Three-dimensional (3D) nnU-Net was employed to calculate a novel spatial abnormality map by T1-weighted images and 281 RRMS patients (Dataset-1, male/female = 101/180, median age [range] = 35.0 [17.0, 65.0] years) were categorized into subtypes. Comparison of clinical and MRI features between RRMS subtypes was conducted by Kruskal-Wallis test. Kaplan-Meier analysis was conducted to investigate disability progression in RRMS subtypes. Additional validation using two other RRMS datasets (Dataset-2, n = 33 and Dataset-3, n = 56) was conducted. Five RRMS subtypes were identified: (1) a Frontal-I subtype showing preserved cognitive performance and mild physical disability, and low risk of disability worsening; (2) a Frontal-II subtype showing low cognitive scores and severe physical disability with significant brain volume loss, and a high propensity for disability worsening; (3) a temporal-cerebellar subtype demonstrating lowest cognitive scores and severest physical disability among all subtypes but remaining relatively stable during follow-up; (4) an occipital subtype demonstrating similar clinical and imaging characteristics as the Frontal-II subtype, except a large number of relapses at baseline and preserved cognitive performance; and (5) a subcortical subtype showing preserved cognitive performance and low physical disability but a similar prognosis as the occipital and Frontal-II subtypes. Additional validation confirmed the above findings. Spatial abnormality maps can explain heterogeneity in cognitive and physical performance in RRMS and may contribute to stratified management. Question Can a deep learning algorithm characterize the brain abnormalities associated with the cognitive and physical performance of patients with RRMS? Findings Five RRMS subtypes were identified by the algorithm that demonstrated variable cognitive and physical performance. Clinical relevance The spatial abnormality maps derived RRMS subtypes had distinct cognitive and physical performances, which have a potential for individually tailored management.

Impact of Multiple Sclerosis on different life dimensions among working women in Sweden

Abstract Introduction Multiple sclerosis (MS), like many other chronic diseases, may impact the whole life situation. MS is more common among women than men, in addition, women tend to report worse health status. We aimed to explore the self-reported impact of MS on different dimensions of life such as work, family, leisure activities and, contact with friends and acquaintances. Methods All individuals 20-50 years of age listed in the Swedish MS Registry were invited to answer a survey in 2021. Responses from 2659 working women regarding impact of MS in different dimensions (1, not at all; 2-3, occasionally; 4-5, frequently; 6-7 to a high extend) were explored with descriptive statistics. Results Reported impact of MS varied across the different life dimensions. Working women reported that MS had a greater impact on their leisure activities (20.7% - responding to ‘to a high extent’), followed by contact with friends and acquaintances (15.8%), work (15.5%) and family (11.7%). This despite the fact that 77.1% had mild levels of disability. Further, the MS diagnosis was reported to have contributed to reduced working time (31.4%), refrained from changing job (28.8%), changed jobs (20.5%) or changed career track (20.4%). When questioned about positive life-changing experiences due to MS diagnosis, a majority of the women stated that it had contributed to learning how to adapt to things one cannot change (59.2%) and being grateful for everyday (51.7%). Conclusions An MS diagnosis can significantly impact various aspects of life. While work is notably affected, leisure activities also undergo substantial changes after MS diagnosis. However, acceptance, adaptability and finding meaning, among other, can be important parts of the journey. Key messages • At early stages of MS, the disease tend to affect leisure activities more than other dimensions of life. • Finding coping mechanisms to handle MS may contribute to compensate the impact of MS.

Reasons for Hospital Admission in Individuals With Multiple Sclerosis.

Health care utilization is higher in individuals with multiple sclerosis (MS) than in the general population. However, there are limited data on the reasons for their hospital admissions. Our primary objective is to analyze the reasons for the hospitalization of individuals with MS with the goal of identifying preventable causes. We conducted a retrospective analysis of a cohort of adults with a confirmed diagnosis of MS admitted to Duke University Hospital between January 2018 and January 2020. This yielded a cohort of 210 individuals. Data were analyzed using descriptive statistics. The most common reason for admission was urinary tract infection (UTI; 10.3%). The average length of stay was 6.1 days for the individuals with MS vs 5.5 days for the general population. The 30-day readmission rates were 14.9% and 15.5%, respectively. A significant number of admitted patients were not on any disease-modifying therapy (DMT), and no difference in median age was identified between those with a DMT vs those without. Length of stay and readmission rates were similar to those of the general population in this contemporary cohort. Given the prevalence of bladder dysfunction in MS, it is not surprising that a UTI was the most common reason for admission. Actively addressing management of and techniques for bladder dysfunction may decrease the admission rate for individuals with MS. Though we now have more treatment options for MS, many individuals with the highest health care utilization are not on a DMT. Future research is needed to identify the factors that can be addressed to support these patients and reduce preventable hospitalizations.

Self-esteem and illness perception in multiple sclerosis: Unveiling key factors for self-management

Abstract Background Multiple sclerosis (MS) is characterized by demyelination and variable symptomatology, and typically appears during young adulthood, making it a condition of considerable public health concern. Given its chronic nature, understanding of the illness perception plays a crucial role in long-term disease management. Our research aims to examine the factors affecting illness perception among people with MS. Methods The study sample consisted of 166 patients with MS (75.3% women; mean age: 40.9±11.3 years; mean disease duration: 11.6±7.1 years). People with MS underwent medical examination to assess their functional disability measured by Expanded Disability Status Scale (EDSS), and structured interview, during which data on age, sex, education, employment status, income and disease duration were obtained. Finally, they were asked to fill in the Brief Illness Perception Questionnaire (BIPQ), and the Rosenberg Self-esteem Scale (RSE). Data were analysed with multiple linear regression analysis. Results Our results showed an association between functional disability and illness perception (β = 0.22; p < 0.05). However, this association lost its significance upon adding self-esteem into the model (β=-0.53; p < 0.001), with overall explained variance in illness perception rising from 2.7% to 27.5%. No statistically significant contribution of other socio-demographic or clinical variables was observed. Conclusions Higher self-esteem in people with MS appears to be intricately connected to their illness perception. Given that the management of chronic conditions heavily relies on patients’ personal resources, healthcare providers could play a crucial role in fostering self-esteem. By encouraging the development of self-esteem, patients may come to view their illness as more manageable and less daunting, potentially leading to mitigation of negative consequences of functional disability. [Grant support: VEGA 1/0608/23] Key messages • Self-esteem may be stronger predictor of illness perception than functional disability in people with MS. • MS patients may benefit from psychological support aimed at promoting self-esteem.

Phenotypes of Italian workers with disability: a cluster analysis on workers with multiple sclerosis

Abstract Background While job maintaining/reintegrating are clearly complex issues in multiple sclerosis (MS), where many aspects (physical, psychological, relational and personal resources) can play a key role, they offer scope for potential interventions. This study aimed to identify and describe phenotypes of workers with MS considering specific work-related domains such as work-related difficulties, anxiety and depressive symptoms, and coping strategies. Methods A cross-sectional online survey on MS workers was conducted in Italy. Hierarchical cluster analysis was performed by the Ward method followed by k-means cluster analysis. Results A total of 209 workers with MS were included in the analysis. We identified four phenotypes: phenotype 1 had low work difficulties, low depressive symptoms and mild anxiety, with a moderate tendency to use problem focus and positive attitude and a mild one to use social support as coping strategies (n = 82, 39.2%); phenotype 2 had low-to-mild work difficulties, mild anxiety and low depressive symptoms, with a high tendency to use positive attitude and religion, moderate problem focus and social support, and mild denial (n = 38, 18.7%); phenotype 3 had low-to-mild work difficulties, moderate anxiety and depressive symptoms, with a mild tendency to use problem focus, positive attitude, religion, social support, denial as coping strategies (n = 50, 23.9%); phenotype 4 had mild-to-moderate work difficulties, moderate anxiety and depressive symptoms, with a moderate tendency to use problem focus, positive attitude, and mild social support and denial as coping strategies (n = 39, 18.7%) Conclusions This explorative analysis aimed to find distinct workers with MS profiles in a working-age population based on work-related domains such as work-related difficulties, coping strategies, and psychological aspects. This could lead to a better tailoring of the vocational rehabilitation interventions for workers with MS. Key messages • This approach, in which different domains related to work are considered, could help to identify a taxonomy that recognizes distinct and predominant MS worker phenotypes. • Identification of subgroup MS workers, could result in better tailoring of the vocational rehabilitative interventions for people with MS.

Cerebellar rTMS for Enhancing Coordination in Patients with Multiple Sclerosis: A Narrative Review

Purpose of Review: Cerebellar repetitive transcranial magnetic stimulation (rTMS) has gained attention as a potential therapeutic intervention for neurological disorders. Recently, there has been growing interest in its use to improve coordination in patients with multiple sclerosis (PwMS). This review aims to examine and discuss the current evidence on the effectiveness of cerebellar rTMS in enhancing motor coordination in individuals with MS. Methods: A comprehensive search of Science Direct, PubMed, and Google Scholar was conducted using keywords such as multiple sclerosis, cerebellar repetitive transcranial magnetic stimulation, coordination, and neurorehabilitation. Articles published from January 2012 to July 2024 were included, and only English-language studies were reviewed. Unpublished manuscripts, conference abstracts, and studies not involving larger scientific investigations were excluded. Results: The findings suggest that cerebellar rTMS, when combined with conventional rehabilitation methods, has the potential to improve coordination in PwMS. However, the available evidence is limited, and larger, more rigorous studies are needed to confirm these findings and establish standardized treatment protocols. Conclusion: Current literature indicates that cerebellar rTMS holds promise as a supplementary intervention for improving coordination in PwMS. Further high-quality trials are required to support its clinical application and to better understand the underlying mechanisms.

Exposome, oxidative stress and inflammation in multiple sclerosis: the EXPOSITION study protocol

Abstract Background The functional exposome approach examines the relationship between biological effects (internal exposome) and the sum of environmental exposures (external exposome). Multiple sclerosis (MS) is characterized by selective demyelination and acute inflammation; miRNAs and microbiota are emerging in the pathogenesis as inflammation and oxidative stress biomarkers. The EXPOSITION study protocol has been designed to study such biomarkers variation in response to the external exposome (air pollution, urbanization, lifestyles) in people with MS (pwMS). Methods EXPOSITION is a cross-sectional observational study collecting a sample of 200 pwMS residing in Lombardy, Northern Italy. Sample size is based on the prediction of differential expression of candidate miRNAs through bioinformatic analyses. All participants will be investigated for social, demographic and clinical data as well as general and specific external exposome factors. The internal exposome factors will be collected for each participant from blood and stool samples, as well as from nasal swabs. Exposome clustering and correlation statistical techniques will be applied and variation of miRNA and microbiota will be tested in association with the variation of the external exposome in urban and extra-urban environments. Results and conclusions The expected results will help pwMS and researchers understanding which biomarkers and which components of the external exposome are associated to oxidative stress and inflammation, to improve precision medicine and contrast disease progression. The relationship between urban exposome and biodiversity is an important dimension in the study of environmental impact on human health. This study may provide preliminary data to assess which nature-based solutions are suitable for enhancing the biodiversity of urban areas. Key messages • The functional exposome approach could be used to link environmental risk factors and disease biomarkers using the right methology. • EXPOSITION will quantify the variation of miRNA and microbiota in association with the variation of external exposome, in urban and extra-urban environments.

Costs of Potential Medication Wastage Due to Switching Treatment Among People With Multiple Sclerosis.

Background: Unused medications negatively impact healthcare resource utilization and environmental safety, contribute substantially to annual healthcare expenditures, and may ultimately affect patient health outcomes. People with multiple sclerosis (PwMS) commonly switch disease-modifying therapies (DMTs), leading to medication wastage and substantial costs for insurers and patients. Objectives: To estimate the cost associated with potential medication wastage (PMW) in a subcohort of PwMS receiving oral or self-injectable US Food and Drug Administration-approved DMTs who switched DMTs in a calendar year in the United States. Methods: This retrospective cohort study included adults with MS and used PharMetrics® Plus claims data from 2017 to 2021. PwMS were required to have 12 months of continuous eligibility for the entire year and a claim for at least 2 unique DMTs during the same calendar year. The PMW cohort was defined as those who had an aggregate overlap in days' supply across DMT switches within the year; those in the non-PMW cohort did not. The cost of PMW for insurers and PwMS due to overlap was calculated only at the point of switch to the new DMT and defined as the cost of the remaining days' supply of the prior DMT. Results: The number of PwMS meeting the inclusion criteria was 1762 in 2017, 1947 in 2018, 1679 in 2019, 1461 in 2020, and 1782 in 2021. Approximately 95% of PwMS switched DMTs once within single calendar years, and 25% (n = 381-464) contributed to PMW. For those who had overlapping DMT supply, it was estimated that 34% to 38% of the DMT being switched from was potentially wasted. The total cost of PMW paid by the insurer and PwMS ranged from 1 489 859. While most of the total cost ( 1 450 328) was paid by the insurer, PwMS still owed substantial amounts ( 74 578). Across all PwMS, the per person per year cost ranged from 846. The estimated wastage and associated costs were consistent across all study years. Conclusions: DMT switching is common among PwMS, resulting in PMW and high costs to patients and insurers.

Costs of Potential Medication Wastage Due to Switching Treatment Among People With Multiple Sclerosis

Background: Unused medications negatively impact healthcare resource utilization and environmental safety, contribute substantially to annual healthcare expenditures, and may ultimately affect patient health outcomes. People with multiple sclerosis (PwMS) commonly switch disease-modifying therapies (DMTs), leading to medication wastage and substantial costs for insurers and patients. Objectives: To estimate the cost associated with potential medication wastage (PMW) in a subcohort of PwMS receiving oral or self-injectable US Food and Drug Administration–approved DMTs who switched DMTs in a calendar year in the United States. Methods: This retrospective cohort study included adults with MS and used PharMetrics® Plus claims data from 2017 to 2021. PwMS were required to have 12 months of continuous eligibility for the entire year and a claim for at least 2 unique DMTs during the same calendar year. The PMW cohort was defined as those who had an aggregate overlap in days’ supply across DMT switches within the year; those in the non-PMW cohort did not. The cost of PMW for insurers and PwMS due to overlap was calculated only at the point of switch to the new DMT and defined as the cost of the remaining days’ supply of the prior DMT. Results: The number of PwMS meeting the inclusion criteria was 1762 in 2017, 1947 in 2018, 1679 in 2019, 1461 in 2020, and 1782 in 2021. Approximately 95% of PwMS switched DMTs once within single calendar years, and 25% (n = 381-464) contributed to PMW. For those who had overlapping DMT supply, it was estimated that 34% to 38% of the DMT being switched from was potentially wasted. The total cost of PMW paid by the insurer and PwMS ranged from $1 200 866 to $1 489 859. While most of the total cost ($1 172 140-$1 450 328) was paid by the insurer, PwMS still owed substantial amounts ($28 726-$74 578). Across all PwMS, the per person per year cost ranged from $716 to $846. The estimated wastage and associated costs were consistent across all study years. Conclusions: DMT switching is common among PwMS, resulting in PMW and high costs to patients and insurers.

Quality of life in people with multiple sclerosis vs general population: differences increase by age

Abstract Background To enhance health care for chronically ill people, it is crucial to understand the impact of their disease on health-related quality of life (HRQoL). More than 240,000 people in Germany live with multiple sclerosis (PwMS), the most common immune-mediated neurodegenerative disease of the central nervous system. Little is known about HRQoL in PwMS in comparison to the general population and by subgroups. Methods In 2021, 6,928 statutorily-insured PwMS aged ≥18 years and living in the federal state of Lower Saxony, Germany, were invited to take part in an online survey. The German EQ-5D-5L value set was used to analyse HRQoL by index values. Descriptive subgroup analyses were conducted (age, sex) and compared to a general German reference population (Grochtdreis et al. 2019, DOI: 10.1007/s10198-019-01054-1). Mann-Whitney-U- or Kruskal-Wallis-tests were performed as appropriate. Results Of 1,935 respondents (response rate 27.9%), 1,916 PwMS were included in the current preliminary complete case analysis. HRQoL is reduced in PwMS compared to the general population: Mean (M) 0.67 vs. M 0.88, respectively. While no significant differences by sex were found in PwMS (male: M 0.66 vs. female: M 0.68, p = 0.1), HRQoL decreased with increasing age (p < 0.001). The reduction in HRQoL is more pronounced in PwMS than in the general population (difference between means 0.53 in 18-24 years old to ≥ 75 years old PwMS vs. 0.14 in the reference population, respectively). Conclusions PwMS report an overall lower level of HRQoL compared to the general population. Increasing age correlates with a substantial decrease of HRQoL in PwMS. Targeted research is needed to improve HRQoL of this vulnerable population. Key messages • The decline in HRQoL with increasing age is more pronounced in PwMS than in the general population in Germany. • Further research should focus particularly on the extent to which MS-related factors are solely attributable for the considerable decline of HRQoL in PwMS.

Multiple Sclerosis and Subcutaneous Panniculitis-like T Cell Lymphoma with Hemophagocytic Syndrome: The Role of Treatment Sequencing in the Pathogenetic Mechanism

Introduction: Although panniculitis-like T cell lymphoma (SPTCL) and hemophagocytic syndrome (HSP) have been described as complications following immunosuppressive treatments, there are no reported cases of concomitant SPTCL/HSP and multiple sclerosis (MS). Materials and Methods: We describe the case of a patient affected by an aggressive phenotype of relapsing remitting MS, characterized by consecutive severe relapses with no complete remission. He developed panniculitis-like T cell lymphoma (SPTCL) and hemophagocytic syndrome (HSP) after receiving multiple immunosuppressive treatments in sequence. Despite the aggressive nature of these complications, the patient responded well to a combination of Gemcitabine and Cisplatin. Discussion and Conclusions: With this case, we suggest that physicians always consider blood diseases as possible MS therapy complications, especially in the sequencing setting, and also consider uncommon treatments in those with autoimmune predispositions.