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Objective: To evaluate the relationship between early relapse recovery and onset of progressive multiple sclerosis (MS)., Methods: We studied a population-based cohort (105 patients with relapsing-remitting MS, 86 with bout-onset progressive MS) and a clinic-based cohort (415 patients with bout-onset progressive MS), excluding patients with primary progressive MS. Bout-onset progressive MS includes patients with single-attack progressive and secondary progressive MS. "Good recovery" (as opposed to "poor recovery") was assigned if the peak deficit of the relapse improved completely or almost completely (patient-reported and examination-confirmed outcome measured ≥6 months post relapse). Impact of initial relapse recovery and first 5-year average relapse recovery on cumulative incidence of progressive MS was studied accounting for patients yet to develop progressive MS in the population-based cohort (Kaplan-Meier analyses). Impact of initial relapse recovery on time to progressive MS onset was also studied in the clinic-based cohort with already-established progressive MS (t test)., Results: In the population-based cohort, 153 patients (80.1%) had on average good recovery from first 5-year relapses, whereas 30 patients (15.7%) had on average poor recovery. Half of the good recoverers developed progressive MS by 30.2 years after MS onset, whereas half of the poor recoverers developed progressive MS by 8.3 years after MS onset (p = 0.001). In the clinic-based cohort, good recovery from the first relapse alone was also associated with a delay in progressive disease onset (p < 0.001). A brainstem, cerebellar, or spinal cord syndrome (p = 0.001) or a fulminant relapse (p < 0.0001) was associated with a poor recovery from the initial relapse., Conclusions: Patients with MS with poor recovery from early relapses will develop progressive disease course earlier than those with good recovery., (© 2015 American Academy of Neurology.)

Objective: We examined the effect of relapses-before and after progression onset-on the rate of postprogression disability accrual in a progressive multiple sclerosis (MS) cohort., Methods: We studied patients with primary progressive MS (n = 322) and bout-onset progressive MS (BOPMS) including single-attack progressive MS (n = 112) and secondary progressive MS (n = 421). The effect of relapses on time to Expanded Disability Status Scale (EDSS) score of 6 was studied using multivariate Cox regression analysis (sex, age at progression, and immunomodulation modeled as covariates). Kaplan-Meier analysis was performed using EDSS 6 as endpoint., Results: Preprogression relapses (hazard ratio [HR]: 1.63; 95% confidence interval [CI]: 1.34-1.98), postprogression relapses (HR: 1.37; 95% CI: 1.11-1.70), female sex (HR: 1.19; 95% CI: 1.00-1.43), and progression onset after age 50 years (HR: 1.47; 95% CI: 1.21-1.78) were associated with shorter time to EDSS 6. Postprogression relapses occurred in 29.5% of secondary progressive MS, 10.7% of single-attack progressive MS, and 3.1% of primary progressive MS. Most occurred within 5 years (91.6%) after progressive disease onset and/or before age 55 (95.2%). Immunomodulation after onset of progressive disease course (HR: 0.64; 95% CI: 0.52-0.78) seemingly lengthened time to EDSS 6 (for BOPMS with ongoing relapses) when analyzed as a dichotomous variable, but not as a time-dependent variable., Conclusions: Pre- and postprogression relapses accelerate time to severe disability in progressive MS. Continuing immunomodulation for 5 years after the onset of progressive disease or until 55 years of age may be reasonable to consider in patients with BOPMS who have ongoing relapses., (© 2014 American Academy of Neurology.)