Multiple sclerosis (MS) is a chronic autoimmune inflammatory disease of the central nervous system, leading to neurodegeneration and manifesting as a variety of symptoms. These can include “invisible” symptoms, not externally evident to others, such as fatigue, mood disorders, cognitive impairments, pain, bladder/bowel dysfunction, sexual dysfunction, and vision changes. Invisible symptoms are highly prevalent in people living with MS, with multifactorial etiology and potential to impact the disease course. Patient experiences of these symptoms include both physical and psychosocial elements, which when unaddressed negatively influence many aspects of quality of life and perception of health. Despite the high impact on patient lives, gaps persist in awareness and management of these hidden symptoms. The healthcare provider and patient author experiences brought together here serve to raise the profile of invisible symptoms and review strategies for a team-based approach to comprehensive MS care. We summarize the current literature regarding the prevalence and etiology of invisible symptoms to convey the high likelihood that a person living with MS will contend with one or more of these concerns. We then explore how open communication between people living with MS and their care team, stigma mitigation, and shared decision-making are key to comprehensive management of invisible symptoms. We recommend validated screening tools and technological advancements that may be incorporated into MS care to regularly monitor these symptoms, offering insight into how healthcare providers can both educate and listen to patients, with the goal of improved patient quality of life. By pairing clinical knowledge with an understanding and consideration of the patient perspective, providers will be equipped to foster a patient-centered dialogue that encourages shared decision-making. Invisible symptoms of MS Graphical Plain Language Summary

Incomplete relapse recovery contributes to disability accrual and earlier onset of secondary progressive multiple sclerosis. We sought to investigate the effect of age on relapse recovery. We identified patients with multiple sclerosis from two longitudinal prospective studies, with an Expanded Disability Status Scale (EDSS) score within 30 days after onset of an attack, and follow-up EDSS 6 months after attack. Adult patients with multiple sclerosis (n = 632) were identified from the Comprehensive Longitudinal Investigations in Multiple Sclerosis at Brigham study (CLIMB), and paediatric patients (n = 132) from the US Network of Paediatric Multiple Sclerosis Centers (NPMSC) registry. Change in EDSS was defined as the difference in EDSS between attack and follow-up. Change in EDSS at follow-up compared to baseline was significantly lower in children compared to adults (P = 0.001), as were several functional system scores. Stratification by decade at onset for change in EDSS versus age found for every 10 years of age, EDSS recovery is reduced by 0.15 points (P < 0.0001). A larger proportion of children versus adults demonstrated improvement in EDSS following an attack (P = 0.006). For every 10 years of age, odds of EDSS not improving increase by 1.33 times (P < 0.0001). Younger age is associated with improved recovery from relapses. Age-related mechanisms may provide novel therapeutic targets for disability accrual in multiple sclerosis.

Background: Efficacy and safety of inebilizumab for treatment of neuromyelitis optica spectrum disorder in adults seropositive for aquaporin-4 (AQP4)–immunoglobulin (Ig) G were demonstrated in the 28-week randomized controlled period of the N-MOmentum study. Objective: To assess efficacy and safety of long-term inebilizumab treatment. Methods: Post hoc analysis was performed in 75 AQP4–IgG–seropositive participants receiving inebilizumab for ⩾4 years in the randomized controlled period and open-label extension of the N-MOmentum study. Results: Eighteen attacks occurred in 13 participants during inebilizumab treatment (annualized attack rate, 0.052 attacks/person-year). Twelve attacks occurred during the first year of treatment, and two each occurred in years 2–4. Disability scores remained stable throughout ⩾4 years of treatment. Inebilizumab was well tolerated, with two (2.7%) serious treatment-emergent adverse events related to inebilizumab and no deaths. Immunoglobulin G levels decreased over time; however, correlation between severe infections and low IgG levels could not be determined because of their small numbers. Conclusion: These results from the N-MOmentum study continue to support use of inebilizumab for treatment of neuromyelitis optica spectrum disorder. Furthermore, the findings suggest that efficacy of inebilizumab may be enhanced after the first year of treatment, warranting additional long-term investigation.

In the past decade, the therapeutic arsenal for multiple sclerosis has expanded greatly. Newer more potent disease modifying therapies (DMTs) with varying mechanisms of actions are increasingly used early in the disease course. These newer DMTs include oral therapies (teriflunomide, dimethyl fumarate, fingolimod, siponimod, ozanimod, and cladribine) and infusion therapies (natalizumab, alemtuzumab, and ocrelizumab), and are associated with better control of disease activity and long-term outcomes in patients with MS compared to older injectable therapies (interferon beta and glatiramer acetate). However, they are associated with safety concerns and subsequent monitoring requirements. Adverse events are initially observed in phase 2 and 3 clinical trials, and further long-term data are collected in phase 3 extension studies, case series, and post-marketing reports, which highlight the need to periodically re-evaluate and adjust monitoring strategies to optimize treatment safety in an individualized approach.

Multiple sclerosis (MS) is a chronic disease in which the immune system attacks the central nervous system, causing inflammation and neurodegeneration. People living with MS may experience a variety of symptoms as a consequence of this process, including many “invisible” symptoms that are internally manifested and not seen by others. Of the invisible symptoms of MS, which we have reviewed in a companion article, mood and mental health disorders are of particular concern due to their high prevalence and significant impact on patient quality of life. In this review, we showcase the experiences of patient authors alongside perspectives from healthcare provider authors as we promote awareness of the common mental health conditions faced by those living with MS, such as depression, anxiety, adjustment disorder, bipolar disorder, psychosis, and suicidal ideation. Many of these conditions stem in part from the increased stress levels and the many uncertainties that come with managing life with MS, which have been exacerbated by the environment created by the coronavirus disease 2019 (COVID-19) pandemic. A patient-centered interdisciplinary approach, routine screening for mental health changes, and referral to specialists when needed can normalize discussions of mental health and increase the likelihood that people living with MS will receive the support and care they need. Management techniques such as robust social support, cognitive behavioral therapy, mindfulness-based interventions, and/or pharmacotherapy may be implemented to build resilience and promote healthy coping strategies. Increasingly, patients have access to telehealth options as well as digital apps for mental health management. Taken together, these approaches form an integrative care model in which people living with MS benefit from the care of medical professionals, a variety of support networks/resources, and self-management techniques for optimal mental health care. Graphical Plain Language Summary