At the Frontiers of Multiple Sclerosis: Towards an Extension of Clinical Outcome Measures

Dear Colleagues,

Multiple Sclerosis (MS) is an autoimmune-mediated inflammatory, demyelinating, and neurodegenerative disease. The onset is most common in young adults and is more prevalent in women. With its progressive character, it is one of the most frequent physically disabling non-traumatic neurological diseases in early adulthood. Inflammation and neurodegeneration are both linked to increasing neurological and physical impairment, which consequently worsen with the course of the disease. Typical impairments encompass sensory and motor dysfunction of the extremities, visual disturbances, and gait impairment, as well as cognitive dysfunctions. Additionally, a broad range of neuropsychiatric disturbances can also manifest with the disease. These symptoms further compromise a person’s wellbeing and everyday functioning. Amongst others, neuropsychiatric symptoms, such as depression and anxiety but also fatigue and physical inactivity have been highlighted as the most important sequelae of the disease. Although the relationship between certain MS-related impairments and everyday functioning has been the subject of numerous studies, to date, the interaction between physical disability, physical activity, stress, fatigue, and neuropsychiatric symptoms is still underexplored. Particularly, the direction of effects between these variables has not been the focus of existing research and the relationship between physical disability, fatigue, and neuropsychiatric symptoms produced mixed results across different investigations. The diagnostic possibilities offered by advanced imaging-techniques that have been further enriched by eminent biomarkers are shedding new light on disease evolution and have the potential to make diagnosis more reliable and timely. In addition, extended clinical inventories comprising patient-centered measures (PROMs), together with the inclusion of neurobehavioral outcomes and also the direct participation of people with this disease (citizen-science-approach) have substantially contributed to a redefinition of “no evidence of disease activity” (NEDA) and the adoption of this combined endpoint measure has now become mandatory in the overall evaluation of disease-modifying agents (DMDs).

This Special Issue will compile work from different areas of MS-research to enlarge our understanding of pathophysiological mechanisms, clinical variations, and therapeutic strategies in MS. Studies based on clinical and neurobehavioral diagnostics, therapeutic outcomes, and combined measures and markers (e.g., imaging, biomarkers), as well as reviews referring to these issues, in both adult and pediatric MS, are highly welcome.

Prof. Dr. Pasquale Calabrese
Guest Editor

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