Review articleUnderstanding the impact of relapses in the overall course of MS; refinement of the 2 stage natural history model

- Relapse with immediate sequella is common in relapse onset multiple sclerosis (RMS).
- Severe worsening in RMS often occurs stepwise rather than slowly.
- Stepwise worsening at any time is predictive of long term worsening.
- These findings represent a refinement of the 2 stage model of RMS.

Recent studies suggest a need for refinement of the traditional two phase model of relapse onset multiple sclerosis (RMS) to include dynamically changing subgroups within the broad category of secondary progressive MS (SPMS). These studies challenge the traditional notion that relapses play a minor role in comparison to a secondary progressive (perhaps degenerative) process. Patients fulfilling the broad definition for SPMS may take several courses, including variable rates and patterns of overall worsening. New paradigms or models for mapping the trajectory of disability in RMS and SPMS (clinical phenotyping), including periods of remission, may impact our understanding of the underlying pathology, and will be important in assessing treatments.