Progression Independent of Relapse Activity in Multiple Sclerosis: Closer to Solving the Pathologic Puzzle

Progression independent of relapse activity (PIRA) is one of the main mechanisms of disability accrual in multiple sclerosis (MS) even in people with relapsing-remitting MS (RRMS). 1 PIRA can occur at any stage of the disease and is associated with unfavorable long-term outcomes, especially if PIRA occurs early in the disease course. 2 The pathologic substrates of PIRA are not yet well understood, although there is growing evidence suggesting that PIRA may occur mainly in a predominant neurodegenerative context, 3-6 sometimes in combination with an acute inflammatory activity. 2,5 A deeper understanding of the pathologic processes underlying PIRA represents a vital initial stride toward averting the accumulation of irreversible disability in MS.