A journey with no roadmap-The need for validated criteria of the MS prodrome.

BACKGROUND: A growing body of compelling evidence has emerged to validate a set of signs and symptoms that indicates the onset of disease before more typical signs and symptoms present to fulfill a diagnosis of MS. On 24 June 2021, a group of international researchers, patient advocates, and Society representatives led by Professors Helen Tremlett (University of British Columbia) and Ruth Ann Marrie (University of Manitoba) convened virtually for a workshop. OBJECTIVE: Identify key gaps in knowledge, opportunities, and research priorities regarding the prodromal stage of MS. METHODS: The group developed a new framework for MS that includes the stage of early signs and symptoms of MS-and outlined a roadmap to guide future research, with the "goal of preventing the progression to onset of typical symptoms of MS in those who present during the prodromal stage of MS". RESULTS: If high-risk individuals in the early stages of MS can be identified with a high degree of certainty, there is an opportunity to intervene and minimize the risk of progressing to typical MS symptoms and a diagnosis of MS. CONCLUSION: Standardized criteria must be developed, validated, and point of intervention found to better recognize, better diagnose, and better treat MS.

From the prodromal stage of multiple sclerosis to disease prevention.

A prodrome is an early set of signs or symptoms that indicate the onset of a disease before more typical symptoms develop. Prodromal stages are well recognized in some neurological and immune-mediated diseases such as Parkinson disease, schizophrenia, type 1 diabetes mellitus and rheumatoid arthritis. Emerging evidence indicates that a prodromal stage exists in multiple sclerosis (MS), raising the possibility of intervention at this stage to delay or prevent the development of classical MS. However, much remains unclear about the prodromal stage of MS and considerable research is needed to fully characterize the prodrome and develop standardized criteria to reliably identify individuals with prodromal MS who are at high risk of progressing to a diagnosis of MS. In this Roadmap, we draw on work in other diseases to propose a disease framework for MS that incorporates the prodromal stage, and set out key steps and considerations needed in future research to fully characterize the MS prodrome, identify early disease markers and develop standardized criteria that will enable reliable identification of individuals with prodromal MS, thereby facilitating trials of interventions to slow or stop progression beyond the prodrome.