Addition of quantitative MRI to the routine clinical care of patients with multiple sclerosis-Results from the MAGNON project.

BACKGROUND: The revised Lublin classification offers a framework for categorizing multiple sclerosis (MS) according to the clinical course and imaging results. Diagnosis of secondary progressive MS (SPMS) is often delayed by a period of uncertainty. Several quantitative magnetic resonance imaging (qMRI) markers are associated with progressive disease states, but they are not usually available in clinical practice. METHODS: The MAGNON project enrolled 629 patients (early relapsing-remitting MS (RRMS), n = 51; RRMS with suspected SPMS, n = 386; SPMS, n = 192) at 55 centers in Germany. Routine magnetic resonance imaging (MRI) scans at baseline and after 12 months were analyzed using a centralized automatic processing pipeline to quantify lesions and normalized brain and thalamic volume. Clinical measures included relapse activity, disability, and MS phenotyping. Neurologists completed questionnaires before and after receiving the qMRI reports. RESULTS: According to the physicians' reports, qMRI results changed their assessment of the patient in 31.8% (baseline scan) and 27.6% (follow-up scan). For ∼50% of patients with RRMS with suspected SPMS, reports provided additional information that the patient was transitioning to SPMS. In >25% of all patients, this information influenced the physicians' assessment of the patient's current phenotype. However, actual changes of treatment were reported only in a minority of these patients. CONCLUSIONS: The MAGNON results suggest that standardized qMRI reports may be integrated into the routine clinical care of MS patients and support the application of the Lublin classification as well as treatment decisions. The highest impact was reported in patients with suspected SPMS, indicating a potential to reduce diagnostic uncertainty.

Amniotic fluid stem cell-derived extracellular vesicles educate type 2 conventional dendritic cells to rescue autoimmune disorders in a multiple sclerosis mouse model.

Dendritic cells (DCs) are essential orchestrators of immune responses and represent potential targets for immunomodulation in autoimmune diseases. Human amniotic fluid secretome is abundant in immunoregulatory factors, with extracellular vesicles (EVs) being a significant component. However, the impact of these EVs on dendritic cells subsets remain unexplored. In this study, we investigated the interaction between highly purified dendritic cell subsets and EVs derived from amniotic fluid stem cell lines (HAFSC-EVs). Our results suggest that HAFSC-EVs are preferentially taken up by conventional dendritic cell type 2 (cDC2) through CD29 receptor-mediated internalization, resulting in a tolerogenic DC phenotype characterized by reduced expression and production of pro-inflammatory mediators. Furthermore, treatment of cDC2 cells with HAFSC-EVs in coculture systems resulted in a higher proportion of T cells expressing the regulatory T cell marker Foxp3 compared to vehicle-treated control cells. Moreover, transfer of HAFSC-EV-treated cDC2s into an EAE mouse model resulted in the suppression of autoimmune responses and clinical improvement. These results suggest that HAFSC-EVs may serve as a promising tool for reprogramming inflammatory cDC2s towards a tolerogenic phenotype and for controlling autoimmune responses in the central nervous system, representing a potential platform for the study of the effects of EVs in DC subsets.

A new perspective on therapies involving B-cell depletion in autoimmune diseases.

It has been rediscovered in the last fifteen years that B-cells play an active role in autoimmune etiology rather than just being spectators. The clinical success of B-cell depletion therapies (BCDTs) has contributed to this. BCDTs, including those that target CD20, CD19, and BAFF, were first developed to eradicate malignant B-cells. These days, they treat autoimmune conditions like multiple sclerosis and systemic lupus erythematosus. Particular surprises have resulted from the use of BCDTs in autoimmune diseases. For example, even in cases where BCDT is used to treat the condition, its effects on antibody-secreting plasma cells and antibody levels are restricted, even though these cells are regarded to play a detrimental pathogenic role in autoimmune diseases. In this Review, we provide an update on our knowledge of the biology of B-cells, examine the outcomes of clinical studies employing BCDT for autoimmune reasons, talk about potential explanations for the drug's mode of action, and make predictions about future approaches to targeting B-cells other than depletion.

Nurse-led immunotreatment DEcision Coaching In people with Multiple Sclerosis (DECIMS) - A cluster- randomised controlled trial and mixed methods process evaluation.

OBJECTIVE: To evaluate a nurse-led decision coaching programme aiming to redistribute health professionals' tasks to support immunotherapy decision-making in people with multiple sclerosis (MS). METHODS: Cluster-randomised controlled trial with an accompanying mixed methods process evaluation (2014 - 2018). We planned to recruit 300 people with clinically isolated syndrome or relapsing-remitting MS facing immunotherapy decisions in 15 clusters across Germany. Participants in the intervention clusters received up to three decision coaching sessions by a trained nurse and access to an evidence-based online information platform. In the control clusters, participants also had access to the information platform. The primary outcome was informed choice after six months, defined as good risk knowledge and congruent attitude and uptake. RESULTS: Twelve nurses from eight clusters participated in the decision coaching training. Due to insufficient recruitment, the randomised controlled trial was terminated prematurely with 125 participants (n = 42 intervention clusters, n = 83 control clusters). We found a non-significant difference between groups for informed choice favouring decision coaching: odds ratio 1.64 (95% CI 0.49-5.53). CONCLUSIONS: Results indicate that decision coaching might facilitate informed decision-making in MS compared to providing patient information alone. PRACTICE IMPLICATIONS: Barriers have to be overcome to achieve structural change and successful implementation.

Targeted Therapy of Multiple Sclerosis: A Case for Antigen-Specific Tregs.

Multiple sclerosis is an autoinflammatory condition that results in damage to myelinated neurons in affected patients. While disease-modifying treatments have been successful in slowing the progression of relapsing-remitting disease, most patients still progress to secondary progressive disease that is largely unresponsive to disease-modifying treatments. Similarly, there is currently no effective treatment for patients with primary progressive MS. Innate and adaptive immune cells in the CNS play a critical role in initiating an autoimmune attack and in maintaining the chronic inflammation that drives disease progression. In this review, we will focus on recent insights into the role of T cells with regulatory function in suppressing the progression of MS, and, more importantly, in promoting the remyelination and repair of MS lesions in the CNS. We will discuss the exciting potential to genetically reprogram regulatory T cells to achieve immune suppression and enhance repair locally at sites of tissue damage, while retaining a fully competent immune system outside the CNS. In the future, reprogramed regulatory T cells with defined specificity and function may provide life medicines that can persist in patients and achieve lasting disease suppression after one cycle of treatment.

The comparative effects of bone marrow mesenchymal stem cells and supernatant transplantation on demyelination and inflammation in cuprizone model.

BACKGROUND: Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system (CNS) with inflammation and immune dysfunction. OBJECTIVES: We compared the remyelination and immunomodulation properties of mesenchymal stem cells (MSCs) with their conditioned medium (CM) in the cuprizone model. METHODS: Twenty-four C57BL/ 6 mice were divided into four groups. After cuprizone demyelination, MSCs and their CM were injected into the right lateral ventricle of mice. The expression level of IL-1ß, TNF-α, and BDNF genes was evaluated using the qRT-PCR. APC antibody was used to assess the oligodendrocyte population using the immunofluorescent method. The remyelination and axonal repair were studied by specific staining of the LFB and electron microscopy techniques. RESULTS: Transplantation of MSCs and CM increased the expression of the BDNF gene and decreased the expression of IL-1ß and TNF-α genes compared to the cuprizone group, and these effects in the cell group were more than CM. Furthermore, cell transplantation resulted in a significant improvement in myelination and axonal repair, which was measured by luxol fast blue and transmission electron microscope images. The cell group had a higher number of oligodendrocytes than other groups. CONCLUSIONS: According to the findings, injecting MSCs intraventricularly versus cell-conditioned medium can be a more effective approach to improving chronic demyelination in degenerative diseases like MS.

Protocol for a pragmatic randomised controlled feasibility study of MS WorkSmart: an online intervention for Australians with MS who are employed.

INTRODUCTION: Multiple sclerosis (MS) causes a wide variety of symptoms. Loss of income due to sickness and early retirement comprise one-third of the total cost of MS in Australia. An intervention that maximises work productivity and keeps people with MS in the workforce for longer could provide a large societal cost saving and improve quality of life. The aim is to test the feasibility of delivering and evaluating a 10-week digitally delivered intervention called 'MS WorkSmart'. Findings will provide insights into participant profiles and address key methodological and procedural uncertainties (recruitment, retention, intervention adherence and engagement, and selection of primary outcome) in preparation for a subsequent definitive trial. METHODS AND ANALYSIS: A parallel-arm randomised controlled feasibility study, comparing those randomised to receive the MS WorkSmart package plus usual care (n=20) to those receiving usual care only (n=20). Australians with MS, aged 18-60 years, who are employed, and self-report work instability will be recruited from the Australian MS Longitudinal Study. Online surveys, at baseline and 1-month postintervention, will include MS-related work productivity loss and risk of job loss, MS work behaviour self-efficacy, health-related quality of life, fatigue severity, MS symptom impact on work, intention to retire due to MS, MS-related work difficulties, and awareness and readiness for change at work. Qualitative feedback will be obtained via a semistructured survey following the intervention (for participants) and via interviews (coaches). Analyses will be primarily descriptive and focus on the feasibility and acceptability of the intervention and study procedures. Progression criteria will guide decisions around whether to progress to a full trial. ETHICS AND DISSEMINATION: The study has been approved by the University of Tasmania Human Research Ethics Committee (H0024544). Findings will be disseminated via publication in peer-reviewed journals, conference presentations and community presentations. TRIAL REGISTRATION NUMBER: ACTRN12622000826741.

A Rapid Review of Interventions to Improve Care for People Who Are Medically Underserved with Multiple Sclerosis, Diabetic Retinopathy, and Lung Cancer.

In the United States, patients with chronic conditions experience disparities in health outcomes across the care continuum. Among patients with multiple sclerosis, diabetic retinopathy, and lung cancer, there is a lack of evidence summarizing interventions to improve care and decrease these disparities. The aim of this rapid literature review was to identify interventions among patients with these chronic conditions to improve health and reduce disparities in screening, diagnosis, access to treatment and specialists, adherence, and retention in care. Using structured search terms in PubMed and Web of Science, we completed a rapid review of studies published in the prior five years conducted in the United States on our subject of focus. We screened the retrieved articles for inclusion and extracted data using a standard spreadsheet. The data were synthesized across clinical conditions and summarized. Screening was the most common point in the care continuum with documented interventions. Most studies we identified addressed interventions for patients with lung cancer, with half as many studies identified for patients with diabetic retinopathy, and few studies identified for patients with multiple sclerosis. Almost two-thirds of the studies focused on patients who identify as Black, Indigenous, or people of color. Interventions with evidence evaluating implementation in multiple conditions included telemedicine, mobile clinics, and insurance subsidies, or expansion. Despite documented disparities and a focus on health equity, a paucity of evidence exists on interventions that improve health outcomes among patients who are medically underserved with multiple sclerosis, diabetic retinopathy, and lung cancer.

Rehabilitation therapy versus drug-only therapy in patients with multiple sclerosis.

Background/aim: The treatment for multiple sclerosis (MS) does not cure the disease, but it is intended to reduce the intensity, duration, and frequency of symptoms. Rehabilitation therapy (RT), including an individualized physical therapy program (PTP) and adapted occupational therapy (OT), has benefits in terms of aerobic capacity, muscle strength, coordination, and ability to perform activities of daily living (ADL). The primary objective of this study was to examine the efficacy of RT comprising PTP, OT, and drug treatment (DT) versus DT alone in patients with MS. Another objective was to highlight the importance of continuing the PT and OT at home, in the long term, practically for their entire life. Materials and methods: Between 2020 and 2022, a follow-up observational study was conducted that included 77 patients diagnosed with MS, independent in terms of ability to perform ADL, divided into two groups: group A (39 patients who complied with the RT) and group B (38 patients who did not comply). At the beginning and end of the study, the following parameters were assessed: timed walk for 25 feet [Timed 25-Foot Walk test (T25FW test)], dexterity of the upper limbs [9-Hole Peg Test (9HPT)], and cognitive function [Paced Auditory Serial Addition Test (PASAT)]. Results: Significant improvement in the experimental group was observed regarding the mobility and the performance of leg function (T25FW, p < 0.05) and finger dexterity (9HPT, p < 0.05) for the dominant hand. Conclusion: The current study proves the importance of combining DT with RT in MS therapy with clear benefits in regaining muscle strength in the lower limbs, thus improving coordination and balance while walking and improving dexterity in the dominant hand.

Stem Cell-Derived Exosomal MicroRNAs as Novel Potential Approach for Multiple Sclerosis Treatment.

Multiple Sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) characterized by inflammation and demyelination of CNS neurons. Up to now, there are many therapeutic strategies for MS but they are only being able to reduce progression of diseases and have not got any effect on repair and remyelination. Stem cell therapy is an appropriate method for regeneration but has limitations and problems. So recently, researches were used of exosomes that facilitate intercellular communication and transfer cell-to-cell biological information. MicroRNAs (miRNAs) are a class of short non-coding RNAs that we can used to their dysregulation in order to diseases diagnosis. The miRNAs of microvesicles obtained stem cells may change the fate of transplanted cells based on received signals of injured regions. The miRNAs existing in MSCs may be displayed the cell type and their biological activities. Current studies show also that the miRNAs create communication between stem cells and tissue-injured cells. In the present review, firstly we discuss the role of miRNAs dysregulation in MS patients and miRNAs expression by stem cells. Finally, in this study was confirmed the relationship of microRNAs involved in MS and miRNAs expressed by stem cells and interaction between them in order to find appropriate treatment methods in future for limit to disability progression.

Extracellular vesicles containing miR-181a-5p as a novel therapy for experimental autoimmune encephalomyelitis-induced demyelination.

Multiple sclerosis (MS) is an inflammatory demyelinating disorder of the central nervous system. Recent research has revealed that mesenchymal stem cell-derived extracellular vesicles (MSC-EVs), containing specific miRNAs, possess immunomodulatory properties and have demonstrated therapeutic potential in the treatment of MS. This study aimed to investigate the role MSC-EVs, containing microRNA-181a-5p (miR-181a-5p) in both experimental autoimmune encephalomyelitis (EAE), an established animal model of MS, and lipopolysaccharide-stimulated BV2 microglia. We evaluated clinical symptoms and inflammatory responses in EAE mice following intrathecal injections of MSC-EVs. MSC-EVs containing miR-181a-5p were co-cultured with microglia to explore their impact on inflammation and cell pyroptosis. We validated the interaction between miR-181a-5p and its downstream regulators and conducted in vivo verification by injecting manipulated EVs containing miR-181a-5p into EAE mice. Our results demonstrated that MSC-EVs, containing miR-181a-5p reduced the clinical symptoms of EAE mice. Furthermore, we observed downregulation of miR-181a-5p in EAE model mice, and its expression was restored after treatment with MSC-EVs, which corresponded to suppressed microglial inflammation and pyroptosis. Additionally, EVs containing miR-181a-5p mitigated spinal cord injury and demyelination in EAE mice. Mechanistically, ubiquitin-specific protease 15 (USP15) exhibited high expression in EAE mice, and miR-181a-5p was specifically targeted and bound to USP15, thereby regulating the RelA/NEK7 axis. In conclusion, MSC-EVs containing miR-181a-5p inhibit microglial inflammation and pyroptosis through the USP15-mediated RelA/NEK7 axis, thus alleviating the clinical symptoms of EAE. These findings present a potential therapeutic approach for the treatment of MS.

Efficacy and safety of stem cell transplantation for multiple sclerosis: a systematic review and meta-analysis of randomized controlled trials.

Multiple sclerosis (MS) is a common autoimmune neurological disease affecting patients' motor, sensory, and visual performance. Stem Cell Transplantation (SCT) is a medical intervention where a patient is infused with healthy stem cells with the purpose of resetting their immune system. SCT shows remyelinating and immunomodulatory functions in MS patients, representing a potential therapeutic option. We conducted this systematic review and meta-analysis that included randomized control trials (RCTs) of SCT in MS patients to investigate its clinical efficacy and safety, excluding observational and non-English studies. After systematically searching PubMed, Web of Science, Scopus, and Cochrane Library until January 7, 2024, nine RCTs, including 422 patients, were eligible. We assessed the risk of bias (ROB) in these RCTs using Cochrane ROB Tool 1. Data were synthesized using Review Manager version 5.4 and OpenMeta Analyst software. We also conducted subgroup and sensitivity analyses. SCT significantly improved patients expanded disability status scale after 2 months (N = 39, MD = - 0.57, 95% CI [- 1.08, - 0.06], p = 0.03). SCT also reduced brain lesion volume (N = 136, MD = - 7.05, 95% CI [- 10.69, - 3.4], p = 0.0002). The effect on EDSS at 6 and 12 months, timed 25-foot walk (T25-FW), and brain lesions number was nonsignificant. Significant adverse events (AEs) included local reactions at MSCs infusion site (N = 25, RR = 2.55, 95% CI [1.08, 6.03], p = 0.034) and hematological disorders in patients received immunosuppression and autologous hematopoietic SCT (AHSCT) (N = 16, RR = 2.33, 95% CI [1.23, 4.39], p = 0.009). SCT can improve the disability of MS patients and reduce their brain lesion volume. The transplantation was generally safe and tolerated, with no mortality or significant serious AEs, except for infusion site reactions after mesenchymal SCT and hematological AEs after AHSCT. However, generalizing our results is limited by the sparse number of RCTs conducted on AHSCT. Our protocol was registered on PROSPERO with a registration number: CRD42022324141.

Conversion of Astrocyte Cell Lines to Oligodendrocyte Progenitor Cells Using Small Molecules and Transplantation to Animal Model of Multiple Sclerosis.

Astrocytes, the most prevalent cells in the central nervous system (CNS), can be transformed into neurons and oligodendrocyte progenitor cells (OPCs) using specific transcription factors and some chemicals. In this study, we present a cocktail of small molecules that target different signaling pathways to promote astrocyte conversion to OPCs. Astrocytes were transferred to an OPC medium and exposed for five days to a small molecule cocktail containing CHIR99021, Forskolin, Repsox, LDN, VPA and Thiazovivin before being preserved in the OPC medium for an additional 10 days. Once reaching the OPC morphology, induced cells underwent immunocytofluorescence evaluation for OPC markers while checked for lacking the astrocyte markers. To test the in vivo differentiation capabilities, induced OPCs were transplanted into demyelinated mice brains treated with cuprizone over 12 weeks. Two distinct lines of astrocytes demonstrated the potential of conversion to OPCs using this small molecule cocktail as verified by morphological changes and the expression of PDGFR and O4 markers as well as the terminal differentiation to oligodendrocytes expressing MBP. Following transplantation into demyelinated mice brains, induced OPCs effectively differentiated into mature oligodendrocytes. The generation of OPCs from astrocytes via a small molecule cocktail may provide a new avenue for producing required progenitors necessary for myelin repair in diseases characterized by the loss of myelin such as multiple sclerosis.

Voiding Phase Dysfunction in Multiple Sclerosis: Contemporary Review of Terminology, Diagnosis, Management, and Future Directions.

Lower urinary tract symptoms (LUTS) are highly prevalent in individuals with multiple sclerosis (MS). However, assessment of these symptoms is often hindered by vague definitions or absence of screening in asymptomatic patients. It is crucial to exercise caution when applying the non-neurogenic definition of urinary retention in this population. For men with MS experiencing persistent and treatment-resistant LUTS, urodynamic studies should be used to identify the underlying causes of symptoms. Although numerous therapies are presently accessible for managing LUTS in MS, there is a need for further investigation into emerging treatments such as percutaneous tibial nerve, and noninvasive brain stimulation.

"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.

Making a difference: neurological support in the community.

Nearly 3 million people in the UK have a neurological condition; stroke, traumatic brain injury, Parkinson's disease, multiple sclerosis, brain tumour, motor neurone disease, among others - all affecting the person for the rest of their life. The NHS provides treatment at the onset of a condition but after that, there is a huge need for ongoing support. Research shows that those who are supported and know more about their condition are less likely to have to call on further in-hospital and GP care. There is enormous scope for improving the quality of life for those with neurological conditions. The right support-therapeutic and social-makes all the difference. The book, which this article is based on, shows how those with neurological conditions benefit from integrated ongoing support provided in the local community and self-help, and how lives can be improved. It explains good practice and encouraging methods in the support and treatment of those with life changing conditions.

The role of multidisciplinary MS care teams in supporting lifestyle behaviour changes to optimise brain health among people living with MS: A qualitative exploration of clinician perspectives.

INTRODUCTION: Healthcare professionals have an important role in advocating for the adoption of a brain-healthy lifestyle for optimal multiple sclerosis (MS) care. Nonetheless, studies to date have mainly focussed on the consumer perspective. Herein, we aimed to explore the current practices of how healthcare professionals support protective, lifestyle-related behaviour changes to optimise brain health among people living with MS (plwMS), and their perspectives of professional roles. METHODS: Australian healthcare professionals were recruited via study advertisements, purposive and snowball sampling, to participate in an online, semi-structured and audio-recorded interview. Clinicians were eligible if they had a minimum of a tertiary Bachelor's degree and 12-months experience working with plwMS, access to the Internet and sufficient time to participant. An inductive, data-driven form of reflexive thematic analysis was undertaken before thematic categorisation of the quotes from transcripts. Data analysis was guided by the methods of Braun and Clark and the study's underpinnings drew on the constructs of the Social Cognitive Theory (SCT). RESULTS: Six physicians, 10 MS nurses, 18 allied health professionals, one exercise therapist and one alternative therapist were interviewed. Three primary themes encompassing the perceived role of healthcare professionals in supporting a brain-healthy lifestyle were identified: (1) the empowering role, (2) collaborative role and (3) communicative role. External factors/forces including time constraints, professional expertise, training and skill set, power dynamics, consumer readiness, health literacy, self-efficacy and motivation are at play, and affect how/when healthcare professionals may support behaviour change to optimise lifelong brain health for plwMS. CONCLUSION: Healthcare professionals recognise their critical role in encouraging and supporting the adoption of a brain-healthy lifestyle to optimise lifelong brain health for plwMS. However, discord is evident when they underestimate the complexity of translating knowledge of lifestyle-related behaviour change(s) into action. Greater awareness must be made in recognising and addressing the bidirectionality of external factors such as those in the SCT, that may influence how behaviour change occurs. PUBLIC CONTRIBUTION: Healthcare professionals volunteered to be interviewed as part of the data collection phase of this study.

Integrating palliative care in patients with advanced multiple sclerosis: a scoping review.

BACKGROUND: Multiple sclerosis (MS) often presents a long and uncertain evolution. Treatment decisions in advanced MS are supported by robust evidence, but recent guidelines have suggested a shift to a palliative approach as the disease progresses. This study aims to describe what is known about the integration of palliative care (PC) in patients with severe MS (cost-effectiveness, moment of reference, and perspective of stakeholders). METHODS: A scoping review was developed, and the Scopus, Medline (PubMed), ISI Web of Knowledge, and SAGE databases were consulted, using the key terms: "multiple sclerosis" AND "palliative care". Studies on the perspectives of patients, caregivers, and health professionals regarding the integration of PC in MS were included. No restrictions were applied regarding the subtype of MS, gender, ethnicity, frequency of use of health services, and language. RESULTS: Of 158 articles identified, 19 were included in the review. Key factors were identified, such as the effectiveness of PC intervention in severe MS, the financial impact of providing PC compared to conventional care, the reduction of symptoms and caregiver burden, and the perception of unmet needs by users, health professionals, and caregivers during the PC approach. CONCLUSIONS: Patients with MS should have access to specialized PC when they reach the severe phase of the disease. Providing a multidisciplinary team to provide targeted consultations based on the patient's needs may be most appropriate. These issues have important implications for the future planning and provision of PC services.

[Treatments for multiple sclerosis: update]. / Traitements de la sclérose en plaques : mise à jour.

The management of multiple sclerosis (MS) has undergone a veritable revolution in recent years, with the arrival of highly effective treatments. In some cases, therapeutic discussions even precede the first clinical signs of the disease. The aim of this review is to present the therapeutic arsenal of progression-preventing treatments available in 2024 for MS, with anti-CD20 antibodies taking pride of place, also available for certain progressive forms of MS. The use of these immunosuppressants requires in-depth knowledge of their mechanisms of action, in order to understand their risks, such as the occurrence of opportunistic infections.

La prise en charge de la sclérose en plaques (SEP) a subi une véritable révolution ces dernières années avec l'arrivée de traitements à haute efficacité. La discussion thérapeutique précède même, dans certains cas, l'apparition des premiers signes cliniques de la maladie. Cet article a pour but de présenter l'arsenal des traitements de fond de la SEP disponibles en 2024. Parmi eux, les anticorps monoclonaux anti-lymphocytes B (anti-CD20) occupent une grande place. Ces derniers sont validés dans la forme poussée-rémission mais aussi pour les formes progressives de la SEP. L'utilisation de ces traitements nécessite une connaissance approfondie de leurs mécanismes d'actions afin de comprendre leurs risques tels que la survenue d'infections opportunistes.

Potential therapeutic and diagnostic approaches of exosomes in multiple sclerosis pathophysiology.

Exosomes are bilayer lipid vesicles that are released by cells and contain proteins, nucleic acids, and lipids. They can be internalized by other cells, inducing inflammatory responses and instigating toxicities in the recipient cells. Exosomes can also serve as therapeutic vehicles by transporting protective cargo to maintain homeostasis. Multiple studies have shown that exosomes can initiate and participate in the regulation of neuroinflammation, improve neurogenesis, and are closely related to the pathogenesis of central nervous system (CNS) diseases, including multiple sclerosis (MS). Exosomes can be secreted by both neurons and glial cells in the CNS, and their contents change with disease occurrence. Due to their ability to penetrate the blood-brain barrier and their stability in peripheral fluids, exosomes are attractive biomarkers of CNS diseases. In recent years, exosomes have emerged as potential therapeutic agents for CNS diseases, including MS. However, the molecular pathways in the pathogenesis of MS are still unknown, and further research is needed to fully understand the role of exosomes in the occurrence or improvement of MS disease. Thereby, in this review, we intend to provide a more complete understanding of the pathways in which exosomes are involved and affect the occurrence or improvement of MS disease.