The Multiple Sclerosis Prodrome: Evidence to Action.

A growing body of work points toward the existence of a clinically symptomatic prodromal phase in multiple sclerosis (MS) that might span 5-10 years or more. A prodrome is an early set of signs or symptoms predating the onset of classical disease, which in turn predates a definitive diagnosis. Evidence for a prodromal phase in MS could have major implications for prevention, earlier recognition and treatment, as well as an improved disease course or prognosis. This Perspective provides a succinct overview of the recent advances in our understanding of the MS prodrome and current key challenges. Many of the MS prodromal features characterized thus far are non-specific and are common in the general population; no single feature alone is sufficient to identify an individual with prodromal MS. Biomarkers may increase specificity and accuracy for detecting individuals in the MS prodromal phase, but are yet to be discovered or formally validated. Progress made in the elucidation of prodromal phases in other neurological and immune-mediated diseases suggests that these barriers can be overcome. Therefore, while knowledge of a prodromal phase in MS remains nascent, how best to move from the rapidly growing evidence to research-related action is critical. Immediate implications include refining the concept of the MS continuum to include a prodromal phase. This will help inform the true "at risk" period when considering exposures that might cause MS. Major long-term implications include the earlier recognition of MS, improved prognosis, through earlier disease management, and the future possibility of MS disease prevention.