The classification of multiple sclerosis (MS) into the two distinct phases of relapsing-remitting and progressive, including primary progressive and secondary progressive phenotypes (PPMS and SPMS, respectively) has long been accepted
however, there are several unmet needs associated with this particular model. The observation that both inflammation and neurodegeneration are present from the onset of MS has resulted in a paradigm shift towards MS as a disease continuum driven by pathological mechanisms underlying clinical progression. Here we report the results from a meeting of Italian MS specialists, exploring the evolving perception of MS pathobiology and its implications for diagnosis and treatment. Insights garnered from the expert panel advocate for a redefined understanding of MS. This expert opinion paper reviews the disease continuum and the intertwined nature of inflammatory and neurodegenerative processes. Also, the need for changes in diagnostic criteria and treatment strategies, including the development of novel biomarkers and new therapies targeting smouldering disease, is discussed.