[XVI Post-ECTRIMS Meeting: review of the new developments presented at the 2023 ECTRIMS Congress (I)]. / XVI Reunión Post-ECTRIMS: revisión de las novedades presentadas en el Congreso ECTRIMS 2023 (I).

The XVI Post-ECTRIMS meeting took place in Seville on 20 and 21 October 2023. This meeting was attended by neurologists specialising in multiple sclerosis (MS) from Spain, who shared a summary of the most interesting innovations at the ECTRIMS congress, which had taken place in Milan the previous week. The aim of this article is to summarise new developments related to the pathogenesis, diagnosis and prognosis of MS. The contributions of innate immunity and central nervous system resident cells, including macrophages and microglia in MS pathophysiology and as therapeutic targets were discussed. Compartmentalised intrathecal inflammation was recognised as central to understanding the progression of MS, and the relationship between inflammatory infiltrates and disease progression was highlighted. Perspectives in demyelinating pathologies were reviewed, focusing on neuromyelitis optica and myelin oligodendrocyte glycoprotein antibody-associated disease, highlighting their pathophysiological and diagnostic differences compared to MS. Advances in neuroimaging were also discussed, and especially the analysis of active chronic lesions, such as paramagnetic rim lesions. In the absence of clinical improvements in trials of remyelinating treatments, methodological strategies to optimise the design of future studies were proposed. Breakthroughs in detecting the prodromal phase of MS, the use of biomarkers in body fluids to assess activity, progression and treatment response, and research on progression independent of flares were addressed. The need to define criteria for radiologically isolated syndrome and to clarify the concept was also discussed.

TITLE: XVI Reunión Post-ECTRIMS: revisión de las novedades presentadas en el Congreso ECTRIMS 2023 (I).La XVI edición de la reunión Post-ECTRIMS se celebró los días 20 y 21 de octubre de 2023 en Sevilla. Este encuentro reunió a neurólogos especialistas en esclerosis múltiple (EM) de España, quienes compartieron un resumen de las innovaciones más destacables del congreso ECTRIMS, acontecido en Milán la semana anterior. El objetivo de este artículo es sintetizar las novedades relativas a la patogenia, el diagnóstico y el pronóstico de la EM. Se destacaron las contribuciones de la inmunidad innata y las células residentes del sistema nervioso central, incluyendo macrófagos y microglía, en la patofisiología de la EM y como objetivos terapéuticos. La inflamación intratecal compartimentada se reconoció como fundamental para entender la progresión de la EM, y destaca la relación entre infiltrados inflamatorios y la evolución de la enfermedad. Se revisaron perspectivas en patologías desmielinizantes, enfocadas en la neuromielitis óptica y la enfermedad asociada a anticuerpos contra la glucoproteína de mielina de oligodendrocitos, subrayando sus distinciones patofisiológicas y diagnósticas con la EM. También se abordaron los avances en neuroimagen, especialmente en el análisis de las lesiones crónicas activas, como las lesiones con borde paramagnético. Ante la ausencia de mejoras clínicas en ensayos de tratamientos remielinizantes, se propusieron estrategias metodológicas para optimizar el diseño de futuros estudios. Se abordaron los avances en la detección de la fase prodrómica de la EM, el uso de biomarcadores en fluidos corporales para evaluar la actividad, la progresión y la respuesta al tratamiento, y la investigación sobre la progresión independiente de la actividad de brote. Además, se debatió sobre la necesidad de definir criterios para el síndrome radiológico aislado o precisar su concepto.

Comparison of the effects of mechanical hippotherapy and Cawthorne-Cooksey exercises in patients with multiple sclerosis: Randomized trial.

BACKGROUND: Patients diagnosed with multiple sclerosis (MS) commonly encounter heightened postural instability and challenges in aligning their eyes, head, and bodily motions while engaging in specific tasks. This study aims to compare the effects of Cawthorne-Cooksey and mechanical hippotherapy exercises on fatigue, balance, gait, dizziness, and life quality in patients with MS. METHODS: The MS patients were randomly divided into Cawthorne-Cooksey (n:25) and mechanical hippotherapy exercise (n:25) groups. In addition to the traditional physical therapy program, Cawthorne-Cooksey and hippotherapy exercises were applied to the groups 3 days a week, for 8 weeks. The trial's clinical number is NCT06005909. The Fatigue Severity Scale (FSS), Fatigue Impact Scale (FIS), Dizziness Handicap Inventory, Tinetti Balance and Gait Assessment Scale, and Ferrans&Powers Quality-of-Life Index were used for pre-and post-treatment assessment. RESULTS: Both groups exhibited a significant decrease in FSS, FIS, and Dizziness Handicap Inventory scores, as well as an increase in Tinetti Balance and Gait Assessment Scale and Ferrans&Powers Quality-of-Life Index scores following treatment. In the inter-group comparison, the Tinetti balance and gait assessment and the Ferrans&Powers quality of life index scores were higher in the hippotherapy group compared to the Cooksey group. CONCLUSIONS: Although both forms of physical activity have demonstrated effectiveness in reducing fatigue among individuals with MS, hippotherapy shows superior efficacy in enhancing balance, gait, and overall quality of life.

Neurological efficacy and safety of mesenchymal stem cells (MSCs) therapy in people with multiple sclerosis (pwMS): An updated systematic review and meta-analysis.

BACKGROUND: Current therapeutic strategies for multiple sclerosis (MS) aim to suppress the immune response and reduce relapse rates. As alternative treatments, mesenchymal stem cells (MSCs) are being explored. MSCs show promise in repairing nerve tissue and reducing autoimmune responses in people with MS (pwMS). OBJECTIVE: This review delves into the literature on the efficacy and safety of MSC therapy for pwMS. METHODS: A comprehensive search strategy was employed to identify relevant articles from five databases until January 2024. The inclusion criteria encompassed interventional studies. Efficacy and safety data concerning MSC therapy in relapsing-remitting MS (RRMS), secondary progressive MS (SPMS), and primary progressive MS (PPMS) groups were extracted and analyzed. RESULTS: A comprehensive analysis encompassing 30 studies revealed that individuals who underwent intrathecal (IT) protocol-based transplantation of MSCs experienced a noteworthy improvement in their expanded disability status scale (EDSS) compared to the placebo group. Weighted mean difference (WMD) was -0.28; 95 % CI -0.53 to -0.03, I2 = 0 %, p-value = 0.028); however, the intravenous (IV) group did not show significant changes in EDSS scores. The annualized relapse rate (ARR) did not significantly decrease among pwMS (WMD = -0.34; 95 % CI -1.05 to 0.38, I2 = 98 %, p-value = 0.357). Favorable results were observed in magnetic resonance imaging (MRI), with only 19.11 % of pwMS showing contrast-enhanced lesions (CEL) in the short term and no long-term MRI activity. The most common complications in both short-term and long-term follow-ups were infection, back pain, and gastrointestinal symptoms. CONCLUSIONS: The study highlights the safety potential of MSC therapy for pwMS. While MRI-based neural regeneration shows significant treatment potential, the effectiveness of MSC therapy remains uncertain due to study limitations and ineffective outcome measures. Further research is needed to establish efficacy and optimize evaluation methods for MSC therapy on pwMS.

Neuroinflammation: From Molecular Basis to Therapy.

Neuroinflammatory conditions in the central nervous system (CNS) are implicated in the pathogenesis of several neuroimmune disorders such as acquired demyelinating syndromes, autoimmune encephalopathies, acute or chronic bacterial and viral CNS infections as well as multiple sclerosis (MS) [...].

Myelin Oligodendrocyte Glycoprotein (MOG)35-55 Mannan Conjugate Induces Human T-Cell Tolerance and Can Be Used as a Personalized Therapy for Multiple Sclerosis.

We have previously performed preclinical studies with the oxidized mannan-conjugated peptide MOG35-55 (OM-MOG35-55) in vivo (EAE mouse model) and in vitro (human peripheral blood) and demonstrated that OM-MOG35-55 suppresses antigen-specific T cell responses associated with autoimmune demyelination. Based on these results, we developed different types of dendritic cells (DCs) from the peripheral blood monocytes of patients with multiple sclerosis (MS) or healthy controls presenting OM-MOG35-55 or MOG-35-55 to autologous T cells to investigate the tolerogenic potential of OM-MOG35-55 for its possible use in MS therapy. To this end, monocytes were differentiated into different DC types in the presence of IL-4+GM-CSF ± dexamethasone (DEXA) ± vitamin D3 (VITD3). At the end of their differentiation, the DCs were loaded with peptides and co-cultured with T cells +IL-2 for 4 antigen presentation cycles. The phenotypes of the DC and T cell populations were analyzed using flow cytometry and the secreted cytokines using flow cytometry or ELISA. On day 8, the monocytes had converted into DCs expressing the typical markers of mature or immature phenotypes. Co-culture of T cells with all DC types for 4 antigen presentation cycles resulted in an increase in memory CD4+ T cells compared to memory CD8+ T cells and a suppressive shift in secreted cytokines, mainly due to increased TGF-ß1 levels. The best tolerogenic effect was obtained when patient CD4+ T cells were co-cultured with VITD3-DCs presenting OM-MOG35-55, resulting in the highest levels of CD4+PD-1+ T cells and CD4+CD25+Foxp3+ Τ cells. In conclusion, the tolerance induction protocols presented in this work demonstrate that OM-MOG35-55 could form the basis for the development of personalized therapeutic vaccines or immunomodulatory treatments for MS.

Clinical and therapeutic challenges of smouldering multiple sclerosis.

INTRODUCTION: Assessment of the clinical course, neuroimaging and histopathological changes suggests that multiple sclerosis (MS) should not be defined merely as a focal inflammatory disease of the central nervous system (CNS) because the essence of the disease is due to a diffuse, 'smouldering', pathophysiological process. STATE OF THE ART: Progression independent of relapse activity (PIRA) is the clinical indicator of smouldering MS. Multiple pathomechanical factors determining smouldering MS have been identified, i.e. continuous activation of microglia, which is the source of smouldering inflammation and the failure of remyelination in MS. CLINICAL IMPLICATIONS: Our paper presents new neuroimaging markers, including paramagnetic rim lesions (PRLs) and slowly expanding lesions (SELs), potential methods for clinical evaluation and promising therapeutic options, i.e. Bruton's tyrosine kinase inhibitors that prevent PIRA in smouldering MS. With the duration of MS, the efficacy of the current immunomodulatory treatment is reduced, and its effect is insufficient to control smouldering MS. FUTURE DIRECTIONS: Innovative insights into the pathophysiology and clinical course warrant the need for a holistic approach to MS. The efforts of clinicians should be aimed at indicating subtle neurological deficits in physical performance and cognitive functioning to characterise the disease progression in its early stages. Undoubtedly, a new era for MS is coming in which new resonance markers will be used together with clinical methods to assess smouldering MS, and the treatment will include combination therapy with consideration of drugs that reduce relapse rates and therapy aimed at inhibiting disease progression.

Occupational Physicians' Management of Workers With Multiple Sclerosis in Italy: Results From a Survey.

BACKGROUND: This study, conducted on a sample of Italian occupational physicians (OPs), aimed to gather data regarding professional activity and their needs in managing workers with multiple sclerosis. METHODS: A convenience sample of OPs recruited by e-mail invitation to the list of Italian Society of Occupational Medicine members was considered. A total of 220 OPs participated between July and October 2022. An ad hoc questionnaire was developed based on previous survey experiences. It investigated, among others, the characteristics of OP respondents, the evaluation of fitness for work issues, and the OP training and updating needs on multiple sclerosis and work. RESULTS: Ninety-one percent of OPs had to assess the fitness for work of workers with multiple sclerosis during their activity. Sixty-four percent experienced particular difficulties in issuing a fitness for work judgment. Regarding the level of knowledge on multiple sclerosis, 54% judged it sufficient. The "Assessment of fitness for work for the specific task" and the "Role of the OPs in identifying reasonable accommodations" were the most interesting training topics regarding MS management in work contexts chosen by the respondents. CONCLUSIONS: The interest in the work inclusion and job retention of people with disability, particularly the aspects linked to the Identification and implementation of reasonable accommodations, will require integration with the occupational safety and health protection system and will undoubtedly impact the OP's activities.

Role of artificial intelligence in multiple sclerosis management.

From a clinical viewpoint, there are enormous obstacles to early detection and diagnosis as well as treatment interventions for multiple sclerosis (MS). With the growing application of methods based on artificial intelligence (AI) to medical problems, there might be an opportunity for MS specialists and their patients. However, to develop accurate AI models, researchers must first examine large quantities of patient data (demographics, genetics-based information, clinical and radiological presentation) to identify the characteristics that distinguish illness from health. These are seen as promising approaches toward improved disease diagnosis, treatment individualization, and prognosis prediction. When applied to imaging data, the application of AI subdomains, such as machine learning (ML), deep learning (DL), and neural networks, have proven their value in healthcare. The application of AI in MS management marks a milestone within the healthcare sector. Now, as research and applications of AI continue to advance steadily, breakthroughs are coming at an ever-accelerating pace. As MS continues to develop, the integration of AI is more and more necessary for continuing progress in diagnosis and treatment as well as patient outcomes. In the field of multiple sclerosis, these algorithms have been used for many purposes, such as disease monitoring and therapy.

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 single-arm, open-label pilot study of neuroimaging, behavioral, and peripheral inflammatory correlates of mindfulness-based stress reduction in multiple sclerosis.

Multiple sclerosis (MS) is a chronic neurological disease frequently associated with significant fatigue, anxiety, depression, and stress. These symptoms are difficult to treat, and prominently contribute to the decreases in quality of life observed with MS. The underlying mechanisms of these "silent" symptoms are not well understood and include not just the psychological responses to a chronic disease, but also biological contributions from bidirectional psycho-neuro-immune (dys)regulation of systemic inflammatory biology. To address these issues, we conducted a prospective, observational pilot study to investigate the psychological, biological, and neuroarchitecture changes associated with a mindfulness-based stress reduction (MBSR) program in MS. The overarching hypothesis was that MBSR modulates systemic and central nervous system inflammation via top-down neurocognitive control over forebrain limbic areas responsible for the neurobiological stress response. 23 patients were enrolled in MBSR and assessed pre/post-program with structural 3 T MRI, behavioral measures, hair cortisol, and blood measures of peripheral inflammation, as indexed by the Conserved Transcriptional Response to Adversity (CTRA) profile. MBSR was associated with improvements across a variety of behavioral outcomes, as well as on-study enlargement of the head of the right hippocampus. The CTRA analyses revealed that greater inflammatory gene expression was related to worse patient-reported anxiety, depression, stress, and loneliness, in addition to lower eudaimonic well-being. Hair cortisol did not significantly change from pre- to post-MBSR. These results support the use of MBSR in MS and elucidate inflammatory mechanisms related to key patient-reported outcomes in this population.

Extracellular Vesicles in Multiple Sclerosis: Their Significance in the Development and Possible Applications as Therapeutic Agents and Biomarkers.

Extracellular vesicles (EVs) are "micro-shuttles" that play a role as mediators of intercellular communication. Cells release EVs into the extracellular environment in both physiological and pathological conditions and are involved in intercellular communication, due to their ability to transfer proteins, lipids, and nucleic acids, and in the modulation of the immune system and neuroinflammation. Because EVs can penetrate the blood-brain barrier and move from the central nervous system to the peripheral circulation, and vice versa, recent studies have shown a substantial role for EVs in several neurological diseases, including multiple sclerosis (MS). MS is a demyelinating disease where the main event is caused by T and B cells triggering an autoimmune reaction against myelin constituents. Recent research has elucidate the potential involvement of extracellular vesicles (EVs) in the pathophysiology of MS, although, to date, their potential role both as agents and therapeutic targets in MS is not fully defined. We present in this review a summary and comprehensive examination of EVs' involvement in the pathophysiology of multiple sclerosis, exploring their potential applications as biomarkers and indicators of therapy response.

CD19 CAR T cells for multiple sclerosis: Forging further into the new frontier.

The efficacy of CD19 chimeric antigen receptor (CAR) T cells in B cell malignancies has generated recent interest in their application to other B cell-related pathologies, such as autoimmune diseases. Fischbach et al.1 report on the use of CD19 CAR T cells in two patients with progressive multiple sclerosis, demonstrating feasibility and safety for the first time in this disease process.

Results of a feasibility and initial efficacy clinical trial of a high-intensity interval training program using adaptive equipment in persons with multiple sclerosis who have walking disability.

BACKGROUND: High intensity interval training (HIIT) has been identified as potential stimulus for eliciting health-promoting physical activity in an efficient manner among persons with multiple sclerosis (MS). The current study aimed to examine the feasibility and initial efficacy of a 12-week HIIT program using a recumbent stepper (RSTEP) in persons with MS who have walking disability. Feasibility outcomes of interest included process (i.e., recruitment, adherence, and retention rates), resource (i.e., time and monetary costs), management (i.e., data management and safety reporting assessment), and science (i.e., safety, burden, and treatment effect assessment). We hypothesized that 12-weeks of HIIT will be feasible via meeting a priori benchmarks in process, resource, management, and scientific outcomes. The efficacy outcomes of interest included changes in aerobic fitness, physical activity, walking, upper arm function, cognition, fatigue, and depressive symptoms. We hypothesized that 12 weeks of HIIT would result in improvements in aerobic capacity, walking, upper arm function, cognition, fatigue, and depression. METHODS: A pre-post clinical trial design was applied. Participants (N = 16) were recruited and enrolled in the 12-week RSTEP HIIT program who met the following inclusion criteria: age ≥18 years, self-reported diagnosis of MS, Patient Determined Disability Steps scale score 3.0-7.0, relapse free in past 30 days, willing to visit a University Laboratory for study protocol, asymptomatic status for maximal exercise testing, physician approval, and a self-reported ability to speak, read, and understand English. Measures of efficacy outcomes of interest included Six Minute Walk Test (6MW), Timed 25 Foot Walk Test (T25FW), the Brief International Cognitive Assessment in MS (BICAMS), 9-hole peg test (9-HPT), Expanded Disability Status Scale (EDSS), Fatigue Severity Survey (FSS), Hospital Anxiety and Depression Scale (HADS), Godin Leisure Time Exercise Questionnaire (GLTEQ), Multiple Sclerosis Walking Scale-12 (MSWS-12). Participants completed a graded maximal exercise test for measuring aerobic fitness (VO2peak) and prescription of exercise throughout the intervention. All outcomes were measured at baseline, mid-point (6-weeks), and post-intervention (12-weeks). The intervention involved 12 weeks of supervised, individualized HIIT sessions two times per week using RSTEP. The individual HIIT sessions included 10 cycles of 60 s intervals at the work rate associated with 90 % VO2peak followed by 60 s of active recovery intervals, totaling 20 minutes plus 5-minute warm-up and cool-down periods. Process, resources, management, and scientific feasibility outcomes were examined using descriptive statistics, percentage, and frequency analyses. The efficacy of the intervention was assessed using a 1-factor (Time), repeated measure analysis of variance to identify significant changes over time. RESULTS: Fourteen of 16 participants were retained throughout the full study period and adherence with prescribed exercise sessions was 97 %. Twenty-three staff were comprehensively trained across two sites. There was only one adverse event reported that did not impact participation in the study and overall mean satisfaction rating with the program among participants was 4.7/5. There were statistically significant changes in cognitive processing speed (p = 0.002), GLTEQ (p = 0.005), and MSWS-12 (p = 0.04), but not the other outcomes of fitness, arm function, and walking. Of note, there were large effect sizes noted for peak power output (d = 1.10) and FSS (d = 1.05) despite the lack of statistically significant changes CONCLUSION: Feasibility of a 12-week individualized RSTEP HIIT program was established and participants significantly improved on measures of cognition, physical activity, and walking.

Allied health professionals knowledge and clinical practice in telehealth exercise behavioural change for multiple sclerosis.

BACKGROUND: The growing importance of telehealth in multiple sclerosis (MS) necessitates an understanding of current practices and training needs of health professionals. We aimed to evaluate the knowledge, preparedness, and training preferences of Australian allied health professionals (AHPs) in telehealth exercise therapy and exercise behavioural change for MS patients to inform the development of educational training. METHODS: An online survey was completed by 58 Australian AHPs, including 34 physiotherapists, 14 exercise physiologists, and 10 occupational therapists, focusing on their current practices, preparedness, and training preferences in telehealth exercise and behavioural change for MS. The survey included multiple-choice, Likert scale, and free-text response questions. Data were analysed using binary and multinomial logistic regressions. RESULTS: Not all AHPs were aware of MS exercise guidelines (67% awareness), with exercise physiologists showing the highest familiarity. There was a significant understanding of the difference between physical activity and exercise, though definitions often lacked clarity. Most AHPs (91%) employed behavioural change strategies in their practice, especially goal-setting (95%), identifying facilitators (67%), and reinforcing progress (66%). While most (72%) felt prepared in promoting exercise to MS clients, there were differences in confidence levels concerning the prescription, modification, and teaching of telehealth exercise programs, with occupational therapists have significant less confidence in those domains compared to other AHPs. Most AHPs expressed interest in additional training, with a preference for online workshops focusing on exercise prescription for MS, behaviour change, and telehealth delivery methods. CONCLUSION: In our Australian AHP sample we identified that a quarter to a third of AHPs in MS care may not be confident or prepared to promote telehealth exercise and behavioural change to people with MS. Moreover, the findings highlight some disparity in knowledge and confidence levels amongst different AHPs concerning exercise therapy for MS, indicating the need for tailored multidisciplinary training programs. Such programs should address profession-specific educational gaps and training preferences, ensuring effective and safe telehealth exercise prescription in MS care.

The Indian multiple sclerosis and allied demyelinating disorders registry and research network (IMSRN): Inception to reality.

BACKGROUND: Demyelinating disorders of the CNS are a set of chronic, inflammatory, autoimmune conditions. To improve understanding of epidemiology, population characteristics and disease behaviour, an Indian, hospital-based registry has been established to serve as a platform for fostering collaborative research. The following article outlines the development, governance and current status of the Indian Multiple Sclerosis and Allied Demyelinating Disorders Registry and Research Network (IMSRN), the country's first scientific database and dedicated expert research network of these disorders. METHODS: Multiple reviews and stakeholder meetings were held to set up the registry. The IMSRN was formally initiated in August 2021 across 26 tertiary care centres. The registry is governed by the Indian Council of Medical Research (ICMR), New Delhi and its task force committee. The online secure database captures detailed clinical and imaging patient details at baseline and periodic follow up. Periodic meetings of the task force and collaborators are held to discuss the progress, improvements and research proposals. RESULTS: The IMSRN is currently active and recruiting patients following an informed consent. As of current, more than 3336 patients including RIS (N = 8), CIS (N = 134), MS (N = 1674), NMOSD (N= 561), MOGAD (N = 404), ADEM (N = 46), CRION (N = 21), CLIPPERS (N = 2), and GFAP (N =1) have been enrolled. 340 patients, not meeting the diagnostic criteria for any of the aforementioned disease phenotypes are in the others category. Various research proposals are being developed to study different aspects of these disorders. CONCLUSION: The IMSRN has been established with a vision to strengthen our understanding about MS, NMOSD, MOGAD, and other demyelinating disorders. This would help answer important questions related to disease profiles and long-term outcomes of patients in the Indian setting. From the standpoint of clinical practice, therapeutics, patient management, research, and national policy building, IMSRN shall serve as a synergising platform for bridging the gap in the aforementioned areas and guiding future research through national and international collaboration.

Prevalence, treatment and correlates of depression in multiple sclerosis.

BACKGROUND: The prevalence of depression in Multiple Sclerosis (MS) is often assessed by administering patient reported outcome measures (PROMs) examining depressive symptomatology to population cohorts; a recent review summarised 12 such studies, eight of which used the Hospital Anxiety and Depression Scale-Depression (HADS-D). In clinical practice, depression is diagnosed by an individual structured clinical interview; diagnosis often leads to treatment options including antidepressant medication. It follows that an MS population will include those whose current depressive symptoms meet threshold for depression diagnosis, plus those who previously met diagnostic criteria for depression and have been treated such that depressive symptoms have improved below that threshold. We examined a large MS population to establish a multi-attribute estimate of depression, taking into account probable depression on HADS-D, as well as anti-depressant medication use and co-morbidity data reporting current treatment for depression. We then studied associations with demographic and health status measures and the trajectories of depressive symptoms over time. METHODS: Participants were recruited into the UK-wide Trajectories of Outcome in Neurological Conditions-MS (TONiC-MS) study, with demographic and disease data from clinical records, PROMs collected at intervals of at least 9 months, as well as co-morbidities and medication. Interval level conversions of PROM data followed Rasch analysis. Logistic regression examined associations of demographic characteristics and symptoms with depression. Finally, a group-based trajectory model was applied to those with depression. RESULTS: Baseline data in 5633 participants showed the prevalence of depression to be 25.3 % (CI: 24.2-26.5). There were significant differences in prevalence by MS subtype: relapsing 23.2 % (CI: 21.8- 24.5), primary progressive 25.8 % (CI: 22.5-29.3), secondary progressive 31.5 % (CI: 29.0-34.0); disability: EDSS 0-4 19.2 % (CI: 17.8-20.6), EDSS ≥4.5 31.9 % (CI: 30.2-33.6); and age: 42-57 years 27.7 % (CI: 26.0-29.3), above or below this range 23.1 % (CI: 21.6-24.7). Fatigue, disability, self-efficacy and self esteem correlated with depression with a large effect size (>0.8) whereas sleep, spasticity pain, vision and bladder had an effect size >0.5. The logistic regression model (N = 4938) correctly classified 80 % with 93 % specificity: risk of depression was increased with disability, fatigue, anxiety, more comorbidities or current smoking. Higher self-efficacy or self esteem and marriage reduced depression. Trajectory analysis of depressive symptoms over 40 months in those with depression (N = 1096) showed three groups: 19.1 % with low symptoms, 49.2 % with greater symptoms between the threshold of possible and probable depression, and 31.7 % with high depressive symptoms. 29.9 % (CI: 27.6-32.3) of depressed subjects were untreated, conversely of those treated, 26.1 % still had a symptom level consistent with a probable case (CI: 23.5-28.9). CONCLUSION: A multi-attribute estimate of depression in MS is essential because using only screening questionnaires, diagnoses or antidepressant medication all under-estimate the true prevalence. Depression affects 25.3 % of those with MS, almost half of those with depression were either untreated or still had symptoms indicating probable depression despite treatment. Services for depression in MS must be pro-active and flexible, recognising the heterogeneity of outcomes and reaching out to those with ongoing symptoms.

Multiple Sclerosis and COVID-19: Health and healthcare access, health information and consumer co-created strategies for future access at times of crisis.

BACKGROUND: Persons with multiple sclerosis (MS) need regular access to medical services for optimal health outcomes. During the COVID-19 crisis, evidence indicated some detrimental health changes in persons with MS. Maintaining access to healthcare providers and healthcare information may minimise detrimental health changes during times of crisis. In Australia, there is limited evidence of consultation with people who have chronic health conditions or disabilities regarding government decisions to restrict healthcare access and in the provision of health guidance during the COVID-19 crisis. Yet, there are good examples of government consultation with other minority populations in Australia, leading to beneficial outcomes. OBJECTIVE: To identify MS community members' (persons with MS carers, advocates, healthcare providers) concerns about the health and healthcare access of persons with MS, during the second year of the COVID-19 pandemic and to collaborate with consumers in the MS community to co-create strategies to improve future access and health information provision at times of crisis. METHOD: We undertook a consumer-co-created mixed-method study in the second year of the COVID-19 pandemic to identify healthcare access needs for MS. We presented results to our stakeholder group to identify support needs during crises. Persons with MS and care providers in the MS community completed an online survey and online interviews, and the stakeholder group participated in a stakeholder workshop. RESULTS: Forty-four people participated in surveys, 33 completed interviews, and seven stakeholders participated in the stakeholder workshops. Three themes were identified from the surveys and interviews: health concerns, accessing healthcare services and communication sources. Healthcare providers (76.9 % of persons with MS and 77.8 % of care providers) and websites specific to the pandemic (76.9 % of persons with MS and 83.3 % of care providers) were identified by most survey respondents as preferred information sources during the COVID-19 crisis. Consultation with stakeholders resulted in the co-creation of strategies directed at communication, health, and lifestyle, as well as policies and protocols to address the needs of the MS community during crises. CONCLUSION: We listened to persons with MS and care providers to identify strategies to support health-communication, -access, and -lifestyle during crises. Consumer-created strategies are directed at national and local health advocacy organisations and governments. They are relevant for the coordinated healthcare planning of persons with chronic health conditions and disabilities during crises, such as those experienced by persons with MS.