Bridging perspectives on comorbidities in multiple sclerosis: A pilot study with individuals with lived experience and healthcare professionals.

The association between multiple sclerosis (MS) and inflammatory bowel disease (IBD) has been suggested, apart from their common epidemiological and immunological patterns, also due to observations of increased incidence of both IBD among MS patients and MS among IBD patients. We estimated the risk of concurrent IBD and MS comorbidity, using data from all available case-control studies. We calculated the corresponding Risk ratios (RRs) in each included case-control study to express the risk of IBD and MS concurrence at a given population. We performed additional subgroup analyses according to the type of registry from which the data of the cases were exported (IBD or MS registry) and the IBD type (Crohn's disease, CD or Ulcerative colitis, UC). We included 10 studies, comprising a total of 1,086,430 patients (0.08% of them with concurrent IBD and MS). Pooled RR for IBD/MS comorbitity was 1.54 (95% CI 1.40-1.67; p<0.0001) with no differences (p=0.91) among IBD and MS registries (RR 1.53, 95% CI 1.36-1.72, p<0.001 for MS comorbidity in IBD patients vs. RR 1.55, 95% CI 1.32-1.81, p<0.001 for IBD comorbidity in MS patients). No difference was also found on the risk of MS comorbidity among patients with CD or UC (RR 1.52, 95% CI 1.34-1.72, p<0.001 vs. RR 1.55, 95% CI 1.38-1.74, p<0.001; p for subgroup differences: 0.84). In all analyses no evidence of heterogeneity or publication bias was detected. Both IBD and MS patients seem to have a fifty-percent increased risk of MS or IBD comorbidity, respectively, with no apparent differences between patients with CD or UC.

<h3>Objective:</h3> To compare changes in plasma concentrations of Neurofilament light (NfL) and Glial Fibrillary Acidic Protein (GFAP) in individuals with relapsing multiple sclerosis (RMS) vs progressive multiple sclerosis (PMS), treated with anti-CD20 immunotherapy (rituximab or ocrelizumab) <h3>Background:</h3> Blood biomarkers, especially NfL, can augment clinical and radiographic data in MS treatment monitoring. Few studies have investigated longitudinal change in NfL or GFAP in PMS patients taking anti-CD20s or compared changes in these biomarkers between RMS and PMS. <h3>Design/Methods:</h3> Subjects were selected by MS diagnosis, anti-CD20 treatment for at least 6 months, and presence of multiple blood samples in our Center’s Biorepository. Demographic/clinical information was extracted by chart review. SIMOA plasma assays of NfL and GFAP were conducted at baseline and follow-up (between 3 and 12 months) on Quanterix SR-X. Biomarker concentrations were log transformed. Summary statistics and longitudinal regression analyses, correcting for age, were generated. <h3>Results:</h3> 37 subjects and 67 samples were analyzed (n=7 had no follow-up samples between 3 and 12 months). 64.9% were female. RMS (n=19) had mean(SD) age 38.7(9.2). PMS (n=18) had mean age 56.1(10.4). Age-adjusted mean concentrations of NfL and GFAP did not differ significantly between RMS and PMS at baseline. Geometric mean NfL declined between baseline (6.8, 95%CI 4.2–11.0) and follow-up (4.9, 95%CI 3.3–7.3) in RMS but stayed stable in PMS. Geometric mean GFAP increased between baseline (52.4, 95%CI 35.2–77.9) and follow-up (60.8, 95%CI 40.4–91.4) in PMS but stayed stable in RMS. The changes for both NfL and GFAP differed statistically significantly between MS types. <h3>Conclusions:</h3> With anti-CD20 treatment, plasma NfL levels decreased in RMS by 27.6% while staying stable in PMS; GFAP levels increased in PMS by 16% while remaining stable in RMS. Results correlate with clinical evidence showing greater benefit of anti-CD20 immunotherapy in RMS compared to PMS. Future studies will include more subjects, longer observation, and different immunotherapies. <b>Disclosure:</b> Dr. Gross has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for AP Expert Group. The institution of Stefan Sillau has received research support from Alzheimer’s Association. The institution of Stefan Sillau has received research support from Hewitt Family Foundation; State of Colorado. The institution of Stefan Sillau has received research support from PCORI. The institution of Stefan Sillau has received research support from NINR. The institution of Stefan Sillau has received research support from Michael J. Fox Foundation. The institution of Stefan Sillau has received research support from Department of Defense. The institution of Stefan Sillau has received research support from Colorado Department of Public Health and Environment. The institution of Stefan Sillau has received research support from Benign Essential Blepharospasm Research Foundation. Stefan Sillau has a non-compensated relationship as a Statistician with Novartis that is relevant to AAN interests or activities. Stefan Sillau has a non-compensated relationship as a Statistician with Biogen that is relevant to AAN interests or activities. Sean Selva has nothing to disclose. Mrs. Ritchie has nothing to disclose.

The European Charcot Foundation supported the development of a set of surveys to understand current practice patterns for the diagnosis and management of multiple sclerosis (MS) in Europe. Part 2 of the report summarizes survey results related to secondary progressive MS (SPMS), primary progressive MS (PPMS), pregnancy, paediatric MS and overall patient management. A steering committee of MS neurologists developed case- and practice-based questions for two sequential surveys distributed to MS neurologists throughout Europe. Respondents generally favoured changing rather than stopping disease-modifying treatment (DMT) in patients transitioning from relapsing-remitting MS to SPMS, particularly with active disease. Respondents would not initiate DMT in patients with typical PPMS symptoms, although the presence of ≥1 spinal cord or brain gadolinium-enhancing lesion might affect that decision. For patients considering pregnancy, respondents were equally divided on whether to stop treatment before or after conception. Respondents strongly favoured starting DMT in paediatric MS with active disease; recommended treatments included interferon, glatiramer acetate and, in John Cunningham virus negative patients, natalizumab. Additional results regarding practice-based questions and management are summarized. Results of part 2 of the survey of diagnostic and treatment practices for MS in Europe largely mirror results for part 1, with neurologists in general agreement about the treatment and management of SPMS, PPMS, pregnancy and paediatric MS as well as the general management of MS. However, there are also many areas of disagreement, indicating the need for evidence-based recommendations and/or guidelines.

Multiple sclerosis is a chronic autoimmune, inflammatory neurological disease affecting the nervous system. It targets the myelin sheath of the axons and inflicts axonal degeneration. High susceptibility is seen in people of age group 20-40 years. The incidence rate is three times more in females compared to males. There are 4 types of multiple sclerosis, namely relapsing/remitting multiple sclerosis, secondary progressive multiple sclerosis, primary progressive multiple sclerosis, progressive relapsing multiple sclerosis with relapsing-remitting being the predominant type and makes up 85% of the cases. The pathogenesis of multiple sclerosis includes destruction of myelin sheath followed by formation of lesions and inflammation. Environmental factors and genetic variables play major role in development of the disease. Exposure to viral and bacterial agents can also lead to multiple sclerosis. Disease-modifying therapies (DMTs) are the most commonly employed management strategies for treating patients with multiple sclerosis. Conventional drugs like IFN-β-1a and glatiramer acetate are now being replaced by highly effective DMTs and autologous hematopoietic stem cell transplantation. Recently, there has been drastic developments in the management of multiple sclerosis, owing to the discovery of more tailored and individualized treatment protocols catering specifically to patient needs.

A comparison of anxiety symptoms and correlates of anxiety in people with progressive and relapsing-remitting multiple sclerosis

Should Spinal MRI Be Routinely Performed in Patients With Clinically Isolated Optic Neuritis?

Barriers and motivators for tobacco smoking cessation in people with multiple sclerosis

Objectives Smoking is a well-established risk factor that exacerbates multiple sclerosis (MS) progression and increases disease activity. Smoking cessation promotion practices of MS clinicians are not meeting the needs of people with MS (pwMS). This study aimed to explore the current practices and barriers faced by MS clinicians in Germany. Design A qualitative study design, using semi-structured interviews and thematic analysis. Setting Interviews with participants were held online, via telephone or face-to-face at our institute in Hamburg, Germany. Participants We recruited eight neurologists and four MS nurses from hospitals, neurology practices and rehabilitation facilities in Germany via purposive and snowball sampling. Results We identified 27 codes across four themes: (1) knowledge: the 12 participants demonstrated a satisfactory general knowledge of the negative impacts of smoking on MS (2) current practice: significant variability was reported in the current practices, with some clinicians providing detailed advice while others merely assessing smoking status without further advice or assistance. (3) Barriers: key barriers identified included limited consultation time, perceived lack of patient motivation and insufficient availability of resources, like information material, for effective smoking cessation support. (4) Needs and wishes: participants wished for specific smoking cessation courses to which they could refer patients, as well as information material to use during patient counselling. Conclusion The study reveals considerable gaps in the consistency and comprehensiveness of smoking cessation support provided by MS clinicians in Germany. Addressing these gaps through targeted interventions, and improving the availability of information materials could enhance smoking cessation promotion for pwMS.

Objective:To determine the prevalence of comorbidity in the multiple sclerosis (MS) population at the time of MS diagnosis. We also compared the prevalence of comorbidity in the MS population to that in a matched cohort from the general population.Methods:Using population-based administrative health data from 4 Canadian provinces, we identified 23,382 incident MS cases and 116,638 age-, sex-, and geographically matched controls. We estimated the prevalence of hypertension, diabetes, hyperlipidemia, heart disease, chronic lung disease, epilepsy, fibromyalgia, inflammatory bowel disease, depression, anxiety, bipolar disorder, and schizophrenia at MS diagnosis using validated case definitions. We compared the populations using rate ratios.Results:Of the MS cases, 16,803 (71.9%) were female. The most prevalent comorbidity was depression (19.1%). Compared to the matched population, all comorbidities except hyperlipidemia were more common in the MS population. Relative to the matched populations, the prevalence of hypertension was 16% higher for women with MS and 48% higher for men with MS, thus there was a disproportionately higher prevalence of hypertension in men with MS than women. Men with MS also had a disproportionately higher prevalence than women with MS for diabetes, epilepsy, depression, and anxiety.Conclusions:Comorbidity is more common than expected in MS, even around the time of diagnosis. The prevalence of psychiatric comorbidity is particularly high and highlights the need for clinical attention to this issue. The observed sex-specific differences in the burden of comorbidity in MS, which differ from those in the matched population, warrant further investigation.

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system with distinct subtypes, relapsing MS (RMS) and primary progressive MS (PPMS), which differ in clinical course and underlying immunopathology. Cytokines are pleiotropic mediators of inflammatory and regenerative processes and are considered important contributors to the pathophysiology of MS. Ocrelizumab, a CD20-targeting monoclonal antibody, is approved for the treatment of patients with RMS and PPMS, yet its effects on circulating cytokines and neurotrophic factors remain incompletely understood. In this prospective observational study, 84 patients with MS (57 RMS, 27 PPMS) were analyzed regarding demographic data, disease activity and serum cytokine profiles before and 6 months after the start of ocrelizumab therapy. Baseline analyses revealed distinct cytokine signatures between patients with RMS and PPMS, with higher levels of several proinflammatory cytokines and chemokines in patients with RMS. Following ocrelizumab treatment, divergent cytokine profiles between patients with RMS and PPMS were partially attenuated, with significant modulation of Th1-associated chemokines and an increase in brain-derived neurotrophic factor (BDNF) observed in patients with RMS. In contrast, cytokine signatures in patients with PPMS remained largely unaffected by ocrelizumab treatment. Patients with RMS with disease activity during the first 6months of ocrelizumab treatment showed a significant increase in different chemokines compared to baseline compared with patients without disease activity or those with PPMS. Our findings support divergent immunological mechanisms in RMS and PPMS, with a stronger cytokine-driven pathology and more pronounced immunomodulatory effects of ocrelizumab on the cytokine profile in patients with RMS.

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system. Migraine is a common comorbidity in MS, with primary headache syndromes frequently observed. Ofatumumab, a high-efficacy anti-cluster of differentiation 20 (CD20) monoclonal antibody, and erenumab, a calcitonin gene-related peptide (CGRP) receptor antagonist, are available as subcutaneously administered monoclonal antibody agents. Despite their independent efficacy, there is limited evidence regarding the concurrent use of these two agents in patients with MS and migraine, especially in those with dermatological conditions such as pyoderma gangrenosum. We treated a 43-year-old Japanese woman with relapsing-remitting MS (RRMS), migraine, and pyoderma gangrenosum. She experienced persistent migraines despite valproic acid and sumatriptan use. After the administration of intravenous methylprednisolone (IVMP), ofatumumab treatment was introduced; erenumab was later initiated to manage migraines. The addition of erenumab reduced the patient's monthly migraine days (MMDs) and monthly headache days (MHDs). No progression of MS or worsening of pyoderma gangrenosum was observed. The Expanded Disability Status Scale (EDSS) score remained stable, and cognitive function was preserved. The combination therapy demonstrated effectiveness without exacerbating the patient's underlying dermatological condition. This case suggests that combining ofatumumab and erenumab is a viable therapeutic option for patients with MS and comorbid migraine and pyoderma gangrenosum, offering effective disease control with an acceptable safety profile.

It is generally accepted that comorbidity, the presence of one or more co-occurring conditions or diseases, increases with age, and is common in patients with a chronic disease such as multiple sclerosis (MS). And, more importantly, that comorbidity can have many effects such as diagnostic delays, selection of treatment and their outcomes, as well as worsening quality of life, to name a few. However, it is only relatively recently that there has been a focused awareness and interest in the impact of comorbid conditions in MS patients. This is evidenced by the formation of the International Workshop on MS Comorbidities being sponsored by the International Advisory Committee on Clinical trials of the European Committee for Treatment and Research in MS (ECTRIMS) and the National MS Society (NMSS). This workshop is slated for late March, where a group of international MS researchers and clinicians will meet with the aims of better describing the types of comorbidities that commonly occur in MS patients, identifying gaps in the research and suggesting strategies for addressing these gaps. In this special issue of the Multiple Sclerosis Journal, Marrie and colleagues present six papers that provide a comprehensive review of the literature on the incidence and prevalence of a variety of comorbidities in MS. These papers provide a foundation for discussions at the upcoming MS Comorbidities workshop as well as providing the MS field with a compendium of the existing literature on the incidence and prevalence of comorbidities that occur in patients with MS.

Multiple sclerosis (MS) is a complex immune-mediated disease with no currently known cure. There is growing evidence to support the role of diet in reducing some of the symptoms and disease progression in MS, and we previously developed and tested the feasibility of a digital nutrition education program for people with MS. The aim of this study was to explore factors that influenced engagement in the digital nutrition education program, including features influencing capability, opportunity and motivation to change their dietary behaviours. Semi-structured interviews were conducted with people who had MS, and who completed some or all of the program until data saturation was reached. Interviews were analysed inductively using thematic analysis. Themes were deductively mapped against the COM-B (Capability, Opportunity, Motivation, Behaviour) behaviour change model. Sixteen interviews were conducted with participants who completed all (n = 10) or some of the program (n = 6). Four themes emerged: (1) acquiring and validating nutrition knowledge; (2) influence of time and social support; (3) getting in early to improve health and (4) accounting for food literacy experiences. This is the first online nutrition program with suitable behavioural supports for people with MS. It highlights the importance of disease-specific and evidence-based nutrition education to support people with MS to make dietary changes. Acquiring nutrition knowledge, coupled with practical support mechanisms, such as recipe booklets and goal setting, emerged as crucial for facilitating engagement with the program. When designing education programs for people with MS and other neurological conditions, healthcare professionals and program designers should consider flexible delivery and building peer support to address the needs and challenges faced by participants. Members of the MS Nutrition Research Program Stakeholder Reference Group, which includes people with MS and MS health professionals, provided input during the development of the nutrition education program and study design stages.

Classifications of multiple sclerosis subtypes have been largely based on clinical phenomenology. Nevertheless, definitions of relapse, remission and progression have been imprecise. Recently an international consensus group, as part of a reclassification of disease subtypes, recommended dropping the term 'relapsing-progressive' (RP) and retaining the term 'progressive-relapsing' (PR) multiple sclerosis. The term 'RP' multiple sclerosis had been applied when the early course combined both relapses and progression and was believed to identify some patients with a worse than average outcome. The PR group consisted of patients with primary progressive disease who later in their course developed relapses. Since the terminology has been largely arbitrary, we have evaluated the validity of the terms 'RP' and 'PR' multiple sclerosis in the context of long-term outcome within a large population-based cohort of progressive multiple sclerosis patients seen at the London Multiple Sclerosis Clinic (Canada) between 1972 and 1984. Mean follow-up of the entire cohort was 25 years. Designation of RP multiple sclerosis did identify a more rapidly progressive subgroup. To realign these natural history data with consensus recommendations, these patients were reassigned to secondary progressive (SP) or to primary progressive (PP) multiple sclerosis, with progression defined as at least 1 year of progressive deterioration. PP multiple sclerosis patients with relapses after a year were designated as having PR multiple sclerosis. Relapses in primary progressive multiple sclerosis occurred in 27.8% of patients at some point even two to three decades after onset. In general these relapses were mild and remitting, but served to blur the distinction between progressive and relapsing-remitting disease. The long-term outcomes of time to Kurtzke disability scores (DSS) of 3, 6, 8 and 10 were compared among the progressive subtypes. Times to these disability end-points and to death were not different between PR and PP multiple sclerosis. Survival curves for progressive patients have been amended to incorporate the reassignment of PR multiple sclerosis patients into the PP group and the RP multiple sclerosis patients into the PP and SP subgroups. The time to reach DDS 3, 6, 8 and 10 for a population-based cohort of primary and secondary progressive patients resulting from the elimination of the categories of RP multiple sclerosis and PR multiple sclerosis has been established. These results provide justification for retaining only PP and SP multiple sclerosis as the subgroups of progressive disease.

Background: The prevalence of osteoporosis is higher in people with multiple sclerosis (MS) compared with the general population. Poor bone health, including higher rates of osteopenia and osteoporosis than in the general population, has been established in people with MS. This qualitative study examines how much a group of health care professionals (HCPs) knows about osteoporosis as an MS comorbidity, as well as current practices, barriers to effective bone health management in people with MS, and recommendations for improvement. Methods: Thirty-two Australian HCPs participated in qualitative interviews, including 4 neurologists, 8 endocrinologists, 9 MS nurses, 6 general practitioners, and 5 physiotherapists. Participants were recruited via email, phone calls, and network contacts. Due to a technical error with the recording of 1 interview, 31 interviews were transcribed using Otter.ai. They were reviewed for accuracy and analyzed through NVivo using framework analysis. Results: Most clinicians lacked specific knowledge regarding bone health in people with MS. While the heightened osteoporosis risk in people with MS was presumed, participants perceived current practices as insufficient or were uncertain about their adequacy. Lack of awareness and education about bone health in people with MS emerged as primary barriers, as did insufficient interdisciplinary communication, role delegation, funding, and resources, which were deemed essential for better management. Conclusions: Clinicians advocated for specific guidelines, enhanced education for HCPs, increased resources for patients and clinicians, and improved access to bone health screening for people with MS. These findings underscore the need for comprehensive strategies, emphasizing collaboration, education, and resource allocation, to address the complexities of bone health in individuals with MS.