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.
In this Roadmap, Marrie and colleagues set out the steps needed to improve our understanding of the multiple sclerosis (MS) prodrome and develop standardized criteria for identifying individuals with prodromal MS, thereby facilitating trials of interventions that could slow progression to classical MS.
Key points: Emerging evidence supports the existence of a prodromal stage in multiple sclerosis (MS) as established in other neurological and immune-mediated diseases.Revision of the natural history of MS to include the prodromal stage enables the identification of opportunities for future intervention and facilitates the design of clinical trials.Clear research directions are needed to develop standardized criteria for prodromal MS, which will enable the identification of individuals who are at high risk of developing classical MS and who might benefit from intervention.The prodromal stage of MS needs to be fully characterized through prospective studies that focus on informative populations such as people with radiologically isolated syndrome or first-degree relatives with MS.Identification and validation of clinical, genetic, imaging and fluid biomarkers of prodromal MS in diverse populations are needed.