Core data set para la generación de datos de la vida real en esclerosis múltiple: adaptación de una iniciativa global para América Latina / Core data set for real world data in multiple sclerosis: customization for latin america from a global task force recommendation

Introducción: Los objetivos primarios del core data set son reducir la heterogeneidad y promover la armonización entre las fuentes de datos en la esclerosis múltiple (EM), reduciendo así el tiempo necesario para ejecutar esfuerzos en la recolección de datos de vida real. Recientemente, un grupo liderado por la Multiple Sclerosis Data Alliance ha desarrollado un core data set para la recolección de datos del mundo real en EM a nivel global. Nuestro objetivo ha sido adaptar y consensuar este conjunto de datos globales a las necesidades de América Latina para que pueda ser implementado por los registros ya desarrollados y en proceso de desarrollo en la región. Material y métodos. Se conformó un grupo de trabajo regionalmente y se adaptó el core data set creado globalmente (proceso de traducción al español, incorporación de variables regionales y consenso sobre variables que se iban a utilizar). El consenso se obtuvo a través de la metodología Delphi remoto de ronda de cuestionarios y discusión a distancia de las variables del core data set. Resultados: Veinticinco profesionales de América Latina llevaron adelante el proceso de adaptación entre noviembre de 2022 y julio de 2023. Se estableció un acuerdo sobre un core data set de nueve categorías y 45 variables, versión 2023, con la sugerencia de implementarlo en registros desarrollados o en vías de desarrollo y cohortes de EM en la región. Conclusión: El core data set busca armonizar las variables recolectadas por los registros y las cohortes de EM en América Latina con el fin de facilitar dicha recolección y permitir una colaboración entre fuentes. Su implementación facilitará la recolección de datos de vida real y la colaboración en la región.(AU)

Introduction: The primary objective of the core data set is to reduce heterogeneity and promote harmonization among data sources in EM, thereby reducing the time needed to execute real life data collection efforts. Recently, a group led by the Multiple Sclerosis Data Alliance has developed a core data set for collecting real-world data on multiple sclerosis (MS) globally. Our objective was to adapt this global data set to the needs of Latin America, so that it can be implemented by the registries already developed and in the process of development in the region. Material and methods: A working group was formed regionally, the core data set created globally was adapted (translation process into Spanish, incorporation of regional variables and consensus on variables to be used). Consensus was obtained through the remote Delphi methodology of a round of questionnaires and remote discussion of the core data set variables. Results: A total of 25 professionals from Latin America carried out the adaptation process between November 2022 and July 2023. Agreement was established on a core data set of nine categories and 45 variables, version 2023 to suggest its implementation in developed or developing registries, and MS cohorts in the region. Conclusion: The core data set seeks to harmonize the variables collected by registries and cohorts in MS in Latin America in order to facilitate said collection and allow collaboration between sources. Its implementation will facilitate real life data collection and collaboration in the region.(AU)

Influencia de la capacidad manipulativa en la calidad de vida y actividades de la vida diaria en la esclerosis múltiple / Influence of manipulative skills on quality of life and activities of daily living in multiple sclerosis

Introducción: Más de un 50% de los pacientes diagnosticados con esclerosis múltiple (EM) comunican problemas con la función manipulativa e impedimentos en su vida diaria a causa de esta alteración. Por ello, el objetivo del presente estudio es determinar la afectación que la fuerza de pinza, la fuerza de presa y la destreza manipulativa ejercen sobre la calidad de vida y la autonomía personal de las personas diagnosticadas de EM, y estudiar si existe diferencia de estos aspectos entre los distintos tipos de esta enfermedad. Sujetos y métodos: Se contó con una muestra total de 126 participantes, de los cuales 57 fueron controles, y 69, casos. A todos ellos se les evaluó con el Multiple Sclerosis Quality of Life-54, el Nine-Hole Peg Test, la dinamometría de pinza y de presa para la medición de la fuerza, y el índice de Barthel para la evaluación de las actividades básicas de la vida diaria. Resultados: Las personas con EM presentaron peores fuerza de pinza, fuerza de presa, destreza manipulativa, desempeño en actividades básicas de la vida diaria y calidad de vida (p < 0,001). La fuerza de presa es un factor condicionante en el desempeño de actividades básicas y calidad de vida en personas con EM. En cuanto al tipo de EM, el tipo remitente-recurrente presentó mejores valores (p < 0,001).Conclusiones: Los hallazgos de este estudio apuntan a que los pacientes diagnosticados con EM presentan una disminución en la fuerza de pinza, la fuerza de presa, la destreza manipulativa, la calidad de vida y la autonomía en las actividades de la vida diaria en comparación con la población sana.(AU)

Introduction: More than 50% of patients diagnosed with multiple sclerosis report problems with manipulative function and impairments in their daily lives due to this disorder. Therefore, the aim of the present study is to determine how pinch strength, prey strength and manipulative dexterity affect the quality of life and personal autonomy of people diagnosed with multiple sclerosis and to study whether there is a difference in these aspects between different types of multiple sclerosis.Subjects and methods: There was a total sample of 126 participants, of which 57 were controls and 69 cases. All of them were assessed with a Multiple Sclerosis Quality of Life-54 test, Nine-Hole Peg Test and Barthel Index.Results: People with multiple sclerosis have worse pinch strength, prey strenght, manipulative dexterity, performance in basic activities of daily living and quality of life (p < 0.001). Prey strength is a conditioning factor for performance and quality of life in people with multiple sclerosis. As for the type of multiple sclerosis, relapsing-remitting multiple sclerosis presented better values (p < 0.001).Conclusions: The findings of this study point to the fact that patients diagnosed with multiple sclerosis have a decrease in prey strength, pinch strength, manipulative dexterity, quality of life and autonomy in activities of daily living compared to the healthy population.(AU)

"So at least now I know how to deal with things myself, what I can do if it gets really bad again"-experiences with a long-term cross-sectoral advocacy care and case management for severe multiple sclerosis: a qualitative study.

BACKGROUND: Persons with severe Multiple Sclerosis (PwsMS) face complex needs and daily limitations that make it challenging to receive optimal care. The implementation and coordination of health care, social services, and support in financial affairs can be particularly time consuming and burdensome for both PwsMS and caregivers. Care and case management (CCM) helps ensure optimal individual care as well as care at a higher-level. The goal of the current qualitative study was to determine the experiences of PwsMS, caregivers and health care specialists (HCSs) with the CCM. METHODS: In the current qualitative sub study, as part of a larger trial, in-depth semi-structured interviews with PwsMS, caregivers and HCSs who had been in contact with the CCM were conducted between 02/2022 and 01/2023. Data was transcribed, pseudonymized, tested for saturation and analyzed using structuring content analysis according to Kuckartz. Sociodemographic and interview characteristics were analyzed descriptively. RESULTS: Thirteen PwsMS, 12 caregivers and 10 HCSs completed interviews. Main categories of CCM functions were derived deductively: (1) gatekeeper function, (2) broker function, (3) advocacy function, (4) outlook on CCM in standard care. Subcategories were then derived inductively from the interview material. 852 segments were coded. Participants appreciated the CCM as a continuous and objective contact person, a person of trust (92 codes), a competent source of information and advice (on MS) (68 codes) and comprehensive cross-insurance support (128 codes), relieving and supporting PwsMS, their caregivers and HCSs (67 codes). CONCLUSIONS: Through the cross-sectoral continuous support in health-related, social, financial and everyday bureaucratic matters, the CCM provides comprehensive and overriding support and relief for PwsMS, caregivers and HCSs. This intervention bears the potential to be fine-tuned and applied to similar complex patient groups. TRIAL REGISTRATION: The study was approved by the Ethics Committee of the University of Cologne (#20-1436), registered at the German Register for Clinical Studies (DRKS00022771) and in accordance with the Declaration of Helsinki.

An exploration of causal relationships between nine neurological diseases and the risk of breast cancer: a Mendelian randomization study.

BACKGROUND: Some preceding researches have observed that certain neurological disorders, such as Alzheimer's disease and multiple sclerosis, may affect breast cancer risk. However, whether there are causal relationships between these neurological conditions and breast cancer is inconclusive. This study was designed to explore whether neurological disorders affected the risks of breast cancer overall and of the two subtypes (ER+ and ER-). METHODS: In the course of this study, genome-wide association study (GWAS) data for nine neurological diseases (Alzheimer's disease, multiple sclerosis, Parkinson's disease, myasthenia gravis, generalized epilepsy, intracerebral haemorrhage, cerebral atherosclerosis, brain glioblastoma, and benign meningeal tumour) were collected from the Complex Trait Genetics lab and the MRC Integrative Epidemiology Unit, and single-nucleotide polymorphisms (SNPs) extensively associated with these neurological ailments had been recognized as instrumental variables (IVs). GWAS data on breast cancer were collected from the Breast Cancer Association Consortium (BCAC). Two-sample Mendelian randomization (MR) analyses as well as multivariable MR analyses were performed to determine whether these SNPs contributed to breast cancer risk. Additionally, the accuracy of the results was evaluated using the false discovery rate (FDR) multiple correction method. Both heterogeneity and pleiotropy were evaluated by analyzing sensitivities. RESULTS: According to the results of two-sample MR analyses, Alzheimer's disease significantly reduced the risks of overall (OR 0.925, 95% CI [0.871-0.982], P = 0.011) and ER+ (OR 0.912, 95% CI [0.853-0.975], P = 0.007) breast cancer, but there was a negative result in ER- breast cancer. However, after multiple FDR corrections, the effect of Alzheimer's disease on overall breast cancer was not statistically significant. In contrast, multiple sclerosis significantly increased ER+ breast cancer risk (OR 1.007, 95% CI [1.003-1.011], P = 0.001). In addition, the multivariable MR analyses showed that Alzheimer's disease significantly reduced the risk of ER+ breast cancer (IVW: OR 0.929, 95% CI [0.864-0.999], P=0.047; MR-Egger: OR 0.916, 95% CI [0.846-0.992], P=0.031); however, multiple sclerosis significantly increased the risk of ER+ breast cancer (IVW: OR 1.008, 95% CI [1.003-1.012], P=4.35×10-4; MR-Egger: OR 1.008, 95% CI [1.003-1.012], P=5.96×10-4). There were no significant associations between the remainder of the neurological diseases and breast cancer. CONCLUSIONS: This study found the trends towards a decreased risk of ER+ breast cancer in patients with Alzheimer's disease and an increased risk in patients with multiple sclerosis. However, due to the limitations of Mendelian randomization, we cannot determine whether there are definite causal relationships between neurological diseases and breast cancer risk. For conclusive evidences, more prospective randomized controlled trials will be needed in the future.

Effects of microbiome-based interventions on neurodegenerative diseases: a systematic review and meta-analysis.

Neurodegenerative diseases (NDDs) are characterized by neuronal damage and progressive loss of neuron function. Microbiome-based interventions, such as dietary interventions, biotics, and fecal microbiome transplant, have been proposed as a novel approach to managing symptoms and modulating disease progression. Emerging clinical trials have investigated the efficacy of interventions modulating the GM in alleviating or reversing disease progression, yet no comprehensive synthesis have been done. A systematic review of the literature was therefore conducted to investigate the efficacy of microbiome-modulating methods. The search yielded 4051 articles, with 15 clinical trials included. The overall risk of bias was moderate in most studies. Most microbiome-modulating interventions changed the GM composition. Despite inconsistent changes in GM composition, the meta-analysis showed that microbiome-modulating interventions improved disease burden (SMD, - 0.57; 95% CI - 0.93 to - 0.21; I2 = 42%; P = 0.002) with a qualitative trend of improvement in constipation. However, current studies have high methodological heterogeneity and small sample sizes, requiring more well-designed and controlled studies to elucidate the complex linkage between microbiome, microbiome-modulating interventions, and NDDs.

Clinical variables influencing the perception of fatigue in people with multiple sclerosis: a cross-sectional study using FSIQ-RMS.

BACKGROUND: Physical fatigue is one of the most disabling symptoms in people with Multiple Sclerosis (PwMS). Several factors might influence the development of fatigue, such as gender, education, body mass index (BMI), Expanded Disability Status Scale (EDSS), disease duration, working status (Ws), physiotherapy (Ph), and disease-modifying therapies (DMTs). Fatigue Symptoms and Impacts Questionnaire-Relapsing Multiple Sclerosis (FSIQ-RMS) is a patient-reported outcome (PRO) that allows one to define the impact of fatigue in PwMS clearly. This study aimed to assess fatigue impact on PwMS by using FSIQ-RMS. METHODS: The participants were enrolled from May to July 2021 in MS Centers of Sant'Andrea Hospital and Policlinico Umberto I Hospital in Rome. Fatigue was evaluated using the FSIQ-RMS, validated, and culturally adapted in Italian. Clinical and demographic data were collected at the same time. RESULTS: We enrolled 178 PwMS [Female 74.16%; RMS 82.58%, SPMS 17.52%]. FSIQ-RMS scores were significantly correlated with EDSS (p-value < 0.01). Analysis of variance between means showed a statistically significant difference between the BMI groups at the 24hours_FSIQ-RMS score and the 7days_FSIQ-RMS score (p < 0.01), with the lower BMI group having the highest scores. Furthermore, perceived fatigue significantly improved both in subjects performing Ph (p < 0.05) and in those who actively work (p < 0.01). CONCLUSIONS: The use of FSIQ-RMS in a real-world setting confirmed that underweight and high levels of disability are closely related to fatigue. In addition, Ph and active Ws are strongly correlated with fatigue in PwMS.

Pediatric traumatic brain injury and early age multiple sclerosis in Finland: A nationwide register-based cohort study.

OBJECTIVE: Examine the link between pediatric traumatic brain injury (pTBI) and early-onset multiple sclerosis in Finland. METHODS: Conducted nationwide register study (1998-2018) with 28,750 pTBI patients (< 18) and 38,399 pediatric references with extremity fractures. Multiple sclerosis diagnoses from Finnish Social Insurance Institution. Employed Kaplan-Meier and multivariable Cox regression for probability assessment, results presented with 95% CI. RESULTS: Of 66 post-traumatic multiple sclerosis cases, 30 (0.10%) had pTBI, and 36 (0.09%) were in the reference group. Cumulative incidence rates (CIR) in the first 10 years were 46.5 per 100,000 (pTBI) and 33.1 per 100,000 (reference). Hazard ratio (HR) for pTBI was 1.10 (95% CI: 0.56-1.48).Stratified by gender, women's CIR was 197.9 per 100,000 (pTBI) and 167.0 per 100,000 (reference) after 15 years. For men, CIR was 44.6 per 100,000 (pTBI) and 34.7 per 100,000 (reference). In the initial 3 years, HR for female pTBI was 1.75 (95% CI: 0.05-6.32), and between years 3 and 20, it was 1.08 (95% CI: 0.51-1.67). For male patients, HR was 1.74 (95% CI: 0.69-4.39). SIGNIFICANCE: We did not find evidence of an association between pTBI and early-onset multiple sclerosis 20 years post-initial trauma.

Immunopathogenesis of multiple sclerosis: molecular and cellular mechanisms and new immunotherapeutic approaches.

Background: Multiple sclerosis (MS) is a central nervous system (CNS) demyelinating autoimmune disease with increasing global prevalence. It predominantly affects females, especially those of European descent. The interplay between environmental factors and genetic predisposition plays a crucial role in MS etiopathogenesis.Methods: We searched recent relevant literature on reputable databases, which include, PubMed, Embase, Web of Science, Scopus, and ScienceDirect using the following keywords: multiple sclerosis, pathogenesis, autoimmunity, demyelination, therapy, and immunotherapy.Results: Various animal models have been employed to investigate the MS etiopathogenesis and therapeutics. Autoreactive T cells within the CNS recruit myeloid cells through chemokine expression, leading to the secretion of inflammatory cytokines driving the MS pathogenesis, resulting in demyelination, gliosis, and axonal loss. Key players include T cell lymphocytes (CD4+ and CD8+), B cells, and neutrophils. Signaling dysregulation in inflammatory pathways and the immunogenetic basis of MS are essential considerations for any successful therapy to MS. Data indicates that B cells and neutrophils also have significant roles in MS, despite the common belief that T cells are essential. High neutrophil-to-lymphocyte ratios correlate with MS severity, indicating their contribution to disease progression. Dysregulated signaling pathways further exacerbate MS progression.Conclusion: MS remains incurable, but disease-modifying therapies, monoclonal antibodies, and immunomodulatory drugs offer hope for patients. Research on the immunogenetics and immunoregulatory functions of gut microbiota is continuing to provide light on possible treatment avenues. Understanding the complex interplay between genetic predisposition, environmental factors, and immune dysregulation is critical for developing effective treatments for MS.

The possible role of oxidative stress marker glutathione in the assessment of cognitive impairment in multiple sclerosis.

Oxidative stress markers have a distinct role in the process of demyelination in multiple sclerosis. This study investigated the potential correlation of markers of oxidative stress (glutathione [GSH], catalase) with the number of demyelinating lesions and the degree of disability, cognitive deficit, and depression in patients with relapsing-remitting multiple sclerosis (RRMS). Sixty subjects meeting the criteria for RRMS (19 men and 41 women), and 66 healthy controls (24 men, 42 women) were included. In this study, GSH significantly negatively correlated with the degree of cognitive impairment. This is the first study of subjects with RRMS that performed the mentioned research of serum GSH levels on the degree of cognitive damage examined by the Montreal Scale of Cognitive Assessment (MoCA) test. The development of cognitive changes, verified by the MoCA test, was statistically significantly influenced by the positive number of magnetic resonance lesions, degree of depression, expanded disability status scale (EDSS), age, and GSH values. Based on these results, it can be concluded that it is necessary to monitor cognitive status early in RRMS patients, especially in those with a larger number of demyelinating lesions and a higher EDSS level and in older subjects. Also, the serum level of GSH is a potential biomarker of disease progression, which could be used more widely in RRMS.

The effect of multiple sclerosis therapy on gut microbiota dysbiosis: a longitudinal prospective study.

Gut microbiota has complex immune functions, related to different pathologies, including multiple sclerosis (MS).This study evaluated the influence of treatments on gut microbiota in people with MS (PwMS). The research comprised 60 participants, including 39 PwMS and 21 healthy controls (HC). Among the PwMS, 20 were prescribed a disease-modifying therapy (DMT), either interferon beta1a or teriflunomide, while 19 received a combination of classical DMT and an immunoglobulin Y (IgY) supplement. For each participant, two sets of gut samples were collected: one at the study's outset and another after two months. Alpha and beta diversity analyses revealed no significant differences between groups. In comparison to the HC, the MS group exhibited an increase in Prevotella stercorea and a decrease in Faecalibacterium prausnitzii. Following treatment, individuals with MS showed enrichment in Lachnospiraceae and Streptococcus. The second sample, compared to the first one, demonstrated an increase in Bifidobacterium angulatum and a decrease in Oscillospira for individuals with MS. Gut microbiota diversity in PwMS is not significantly different to HC.However, specific taxonomic changes indicate the presence of a dysbiosis state. The use of DMTs and immunoglobulin Y supplements may contribute to alterations in microbial composition, potentially leading to the restoration of a healthier microbiome.

A rapid review of differences in cerebrospinal neurofilament light levels in clinical subtypes of progressive multiple sclerosis.

Background: Multiple sclerosis (MS) is divided into three clinical phenotypes: relapsing-remitting MS (RRMS), secondary progressive MS (SPMS), and primary progressive MS (PPMS). It is unknown to what extent SPMS and PPMS pathophysiology share inflammatory or neurodegenerative pathological processes. Cerebrospinal (CSF) neurofilament light (NfL) has been broadly studied in different MS phenotypes and is a candidate biomarker for comparing MS subtypes. Research question: Are CSF NfL levels different among clinical subtypes of progressive MS? Methods: A search strategy identifying original research investigating fluid neurodegenerative biomarkers in progressive forms of MS between 2010 and 2022 was applied to Medline. Identified articles underwent title and abstract screen and full text review against pre-specified criteria. Data abstraction was limited to studies that measured NfL levels in the CSF. Reported statistical comparisons of NfL levels between clinical phenotypes were abstracted qualitatively. Results: 18 studies that focused on investigating direct comparisons of CSF NfL from people with MS were included in the final report. We found NfL levels were typically reported to be higher in relapsing and progressive MS compared to healthy controls. Notably, higher NfL levels were not clearly associated with progressive MS subtypes when compared to relapsing MS, and there was no observed difference in NfL levels between PPMS and SPMS in articles that separately assessed these phenotypes. Conclusion: CSF NfL levels distinguish individuals with MS from healthy controls but do not differentiate MS subtypes. Broad biological phenotyping is needed to overcome limitations of current clinical phenotyping and improve biomarker translatability to decision-making in the clinic.

BTK inhibition limits microglia-perpetuated CNS inflammation and promotes myelin repair.

In multiple sclerosis (MS), persisting disability can occur independent of relapse activity or development of new central nervous system (CNS) inflammatory lesions, termed chronic progression. This process occurs early and it is mostly driven by cells within the CNS. One promising strategy to control progression of MS is the inhibition of the enzyme Bruton's tyrosine kinase (BTK), which is centrally involved in the activation of both B cells and myeloid cells, such as macrophages and microglia. The benefit of BTK inhibition by evobrutinib was shown as we observed reduced pro-inflammatory activation of microglia when treating chronic experimental autoimmune encephalomyelitis (EAE) or following the adoptive transfer of activated T cells. Additionally, in a model of toxic demyelination, evobrutinib-mediated BTK inhibition promoted the clearance of myelin debris by microglia, leading to an accelerated remyelination. These findings highlight that BTK inhibition has the potential to counteract underlying chronic progression of MS.

People with newly diagnosed multiple sclerosis benefit from a complex preventative intervention-a single group prospective study with follow up.

Background: Newly diagnosed people with multiple sclerosis frequently report fatigue, pain, depression and anxiety. Preventative programmes may be beneficial, but there is limited evidence of their effectiveness, especially long-term follow-up. Methods: The programme consisted of 6-month face to face intervention (an introductory workshop, psychology-led group sessions and individual physical therapy) followed by 6-month self-guided therapy. Outcome measures were taken at baseline, 6 and 12 months. Primary outcomes measures were self-report questionnaires for fatigue, satisfaction with life and disease acceptance. Secondary outcomes were spirometry, spiroergometric parameters and neuroactive steroid levels. Results: From 22 participants enrolled, 17 completed the first 6 months and 13 the follow-up. Fatigue measured on the Fatigue scale for motor and cognitive functions decreased significantly at 6 months (p = 0.035) and at follow-up (p = 0.007). The Modified Fatigue Impact Scale (p = 0.035) and Satisfaction With Life Scale (p = 0.007) significantly increased at follow-up. Spirometry, spiroergometric parameters, steroid hormones and neuroactive steroids levels did not change significantly. Conclusion: This programme reduces fatigue and improves satisfaction with life in this patient group with improvements sustained at 12 months. People who participated more frequently showed greater benefit. Clinical rehabilitation impact: The paper describes the effects of a complex preventative intervention for people with newly diagnosed Multiple Sclerosis. The study found that this programme reduces fatigue and improves satisfaction with life with long-term benefit (at 12-month follow up). The individuals who participated less frequently experienced fewer benefits.

Risk of secondary immune thrombocytopenia following alemtuzumab treatment for multiple sclerosis: a systematic review and meta-analysis.

Object: The purpose of this study was to evaluate the risk of secondary immune thrombocytopenia in multiple sclerosis patients treated with alemtuzumab through a meta-analysis. Methods: We searched databases including PubMed, Web of Science, OVID and EMBASE for studies reporting changes in platelet levels in MS patients treated with alemtuzumab from their inception until May 2023 and performed a meta-analysis. Information and data were screened and extracted by two researchers. The inclusion and exclusion criteria were established according to the PICOS principle. The obtained data were analyzed using the R software meta package and the quality assessment was conducted using Newcastle-Ottawa Scale (NOS). The causes of heterogeneity were analyzed using subgroup analysis and sensitivity analysis. Publication bias was evaluated using funnel plots and Egger test. Results: A total of 15 studies were included, encompassing 1,729 multiple sclerosis patients. Meta-analysis of overall secondary ITP in the included studies yielded a pooled rate of 0.0243. The overall incidence of secondary autoimmune events was 0.2589. In addition, subgroup analysis was applied using study regions and study types. The results showed that the incidence rate of secondary ITP in Europe was about 0.0207, while the incidence of autoimmune events (AEs) was 0.2158. The incidence rate of secondary ITP and AEs in North America was significantly higher than in Europe, being 0.0352 and 0.2622. And the analysis showed that the incidence rates of secondary ITP and AEs in prospective studies were 0.0391 and 0.1771. Retrospective studies had an incidence rate of secondary ITP at 2.16, and an incidence rate of AEs at 0.2743. Conclusion: This study found that there was a certain incidence of Immune thrombocytopenia in multiple sclerosis patients after treatment with alemtuzumab. Alemtuzumab may have some interference with platelet levels, and the mechanism may be associated with Treg cells. But due to the absence of a control group in the included literature, we cannot determine the specific impact of Alemtuzumab on platelet levels in patients with MS. Therefore, clinical physicians should perform a comprehensive assessment of the patient's benefit-to-risk ratio before initiating alemtuzumab. Systematic Review Registration: Inplasy website, DOI number is 10.37766/inplasy2024.3.0007.

Longitudinal determinants of employment status in people with relapsing-remitting multiple sclerosis.

Purpose: To investigate longitudinal relationships between employment status and disease-related, (neuro)psychological, and work-related factors in people with multiple sclerosis (MS). Methods: 170 employed people with MS underwent yearly neurological and neuropsychological examinations to assess MS-related disability and cognitive functioning. Additionally, they completed yearly questionnaires assessing depression, anxiety, fatigue, cognitive complaints, workplace support and coping. Multilevel models for change were fitted to examine progression of these factors over three years, and to assess possible relationships with change in employment status. Results: People with a deteriorated employment status after three years reported more depression (p=0.009), a higher impact of fatigue (p<0.001), more cognitive complaints (p<0.001) and less workplace support (p=0.001) at baseline than people with a stable employment status. There were no differences in progression over time of the examined variables between people with a stable or deteriorated employment status. Conclusion: More depression, a higher impact of fatigue, more cognitive complaints and less workplace support are predictive of a deteriorated employment status after three years in individuals with MS. How these factors progress over time is not different between those with a stable or deteriorated employment. MS-related disability, anxiety, objective cognition and coping were not related to a deterioration in employment status.

Effects of exercise in people with multiple sclerosis: a systematic review and meta-analysis.

Background: A growing body of studies have examined the effect of exercise in people with multiple sclerosis (MS), while findings of available studies were conflicting. This meta-analysis aimed to explore the effects of exercise on balance, walking ability, walking endurance, fatigue, and quality of life in people with MS. Methods: We searched PubMed, Web of Science, Scopus, and Cochrane databases, through March 1, 2024. Inclusion criteria were: (1) RCTs; (2) included an intervention and control group; (3) had people with MS as study subjects; (4) had balance, walking ability, walking endurance, fatigue, or quality of life as the outcome measures. Exclusion criteria were: (1) non-English publications; (2) animal model publications; (3) review articles; and (4) conference articles. A meta-analysis was conducted to calculate weighted mean difference (WMD) and 95% confidence interval (CI). Cochrane risk assessment tool and Physiotherapy Evidence Database (PEDro) scale were used to evaluate the methodological quality of the included studies. Results: Forty studies with a total of 56 exercise groups (n = 1,300) and 40 control groups (n = 827) were eligible for meta-analysis. Exercise significantly improved BBS (WMD, 3.77; 95% CI, 3.01 to 4.53, P < 0.00001), TUG (WMD, -1.33; 95% CI, -1.57 to -1.08, P < 0.00001), MSWS-12 (WMD, -2.57; 95% CI, -3.99 to -1.15, P = 0.0004), 6MWT (WMD, 25.56; 95% CI, 16.34 to 34.79, P < 0.00001), fatigue (WMD, -4.34; 95% CI, -5.83 to -2.84, P < 0.00001), and MSQOL-54 in people with MS (WMD, 11.80; 95% CI, 5.70 to 17.90, P = 0.0002) in people with MS. Subgroup analyses showed that aerobic exercise, resistance exercise, and multicomponent training were all effective in improving fatigue in people with MS, with resistance exercise being the most effective intervention type. In addition, a younger age was associated with a larger improvement in fatigue. Furthermore, aerobic exercise and multicomponent training were all effective in improving quality of life in people with MS, with aerobic exercise being the most effective intervention type. Conclusion: Exercise had beneficial effects in improving balance, walking ability, walking endurance, fatigue, and quality of life in people with MS. Resistance exercise and aerobic exercise are the most effective interventions for improving fatigue and quality of life in people with MS, respectively. The effect of exercise on improving fatigue was associated with the age of the participants, with the younger age of the participants, the greater the improvement in fatigue. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=371056, identifier: CRD42022371056.

Managing multiple sclerosis in individuals aged 55 and above: a comprehensive review.

Multiple Sclerosis (MS) management in individuals aged 55 and above presents unique challenges due to the complex interaction between aging, comorbidities, immunosenescence, and MS pathophysiology. This comprehensive review explores the evolving landscape of MS in older adults, including the increased incidence and prevalence of MS in this age group, the shift in disease phenotypes from relapsing-remitting to progressive forms, and the presence of multimorbidity and polypharmacy. We aim to provide an updated review of the available evidence of disease-modifying treatments (DMTs) in older patients, including the efficacy and safety of existing therapies, emerging treatments such as Bruton tyrosine kinase (BTKs) inhibitors and those targeting remyelination and neuroprotection, and the critical decisions surrounding the initiation, de-escalation, and discontinuation of DMTs. Non-pharmacologic approaches, including physical therapy, neuromodulation therapies, cognitive rehabilitation, and psychotherapy, are also examined for their role in holistic care. The importance of MS Care Units and advance care planning are explored as a cornerstone in providing patient-centric care, ensuring alignment with patient preferences in the disease trajectory. Finally, the review emphasizes the need for personalized management and continuous monitoring of MS patients, alongside advocating for inclusive study designs in clinical research to improve the management of this growing patient demographic.

Functional gradients reveal cortical hierarchy changes in multiple sclerosis.

Functional gradient (FG) analysis represents an increasingly popular methodological perspective for investigating brain hierarchical organization but whether and how network hierarchy changes concomitant with functional connectivity alterations in multiple sclerosis (MS) has remained elusive. Here, we analyzed FG components to uncover possible alterations in cortical hierarchy using resting-state functional MRI (rs-fMRI) data acquired in 122 MS patients and 97 healthy control (HC) subjects. Cortical hierarchy was assessed by deriving regional FG scores from rs-fMRI connectivity matrices using a functional parcellation of the cerebral cortex. The FG analysis identified a primary (visual-to-sensorimotor) and a secondary (sensory-to-transmodal) component. Results showed a significant alteration in cortical hierarchy as indexed by regional changes in FG scores in MS patients within the sensorimotor network and a compression (i.e., a reduced standard deviation across all cortical parcels) of the sensory-transmodal gradient axis, suggesting disrupted segregation between sensory and cognitive processing. Moreover, FG scores within limbic and default mode networks were significantly correlated ( ρ = 0.30 $$ \rho =0.30 $$ , p < .005 after Bonferroni correction for both) with the symbol digit modality test (SDMT) score, a measure of information processing speed commonly used in MS neuropsychological assessments. Finally, leveraging supervised machine learning, we tested the predictive value of network-level FG features, highlighting the prominent role of the FG scores within the default mode network in the accurate prediction of SDMT scores in MS patients (average mean absolute error of 1.22 ± 0.07 points on a hold-out set of 24 patients). Our work provides a comprehensive evaluation of FG alterations in MS, shedding light on the hierarchical organization of the MS brain and suggesting that FG connectivity analysis can be regarded as a valuable approach in rs-fMRI studies across different MS populations.

Multimodal exercise training to reduce frailty in people with multiple sclerosis: study protocol for a pilot randomized controlled trial.

BACKGROUND: Frailty, a syndrome characterized by decreased reserve and resistance to stressors across multiple physiologic systems, is highly prevalent in people living with multiple sclerosis (pwMS), independent of age or disability level. Frailty in MS is strongly associated with adverse clinical outcomes, such as falls, and may aggravate MS-related symptoms. Consequently, there is a pressing necessity to explore and evaluate strategies to reduce frailty levels in pwMS. The purpose of this pilot randomized controlled trial (RCT) will be to examine the feasibility and preliminary efficacy of a multimodal exercise training program to reduce frailty in pwMS. METHODS: A total of 24 participants will be randomly assigned to 6 weeks of multimodal exercise or to a waitlist control group with a 1:1 allocation. PwMS aged 40-65 years and living with frailty will be eligible. The multimodal exercise program will consist of cognitive-motor rehabilitation (i.e., virtual reality treadmill training) combined with progressive, evidence-based resistance training. At baseline and post-intervention, participants will complete the Evaluative Frailty Index for Physical Activity (EFIP), measures of fall risk, and quality of life. Frailty-related biomarkers will also be assessed. In addition, the feasibility of the multimodal exercise program will be systematically and multidimensionally evaluated. DISCUSSION: To date, no RCT has yet been conducted to evaluate whether targeted exercise interventions can minimize frailty in MS. The current study will provide novel data on the feasibility and preliminary efficacy of multimodal exercise training as a strategy for counteracting frailty in pwMS. TRIAL REGISTRATION: ClinicalTrials.gov, NCT06042244 (registered in September 2023).