Poor early relapse recovery affects onset of progressive disease course in multiple sclerosis

Abstract

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 5 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 5 0.001) or a fulminant relapse (p , 0.0001) was associated with a poor recovery from the initial relapse. In multiple sclerosis (MS), the ability of some patients to recover faster and better than others is an important but poorly understood observation. Predictors of incomplete recovery are older patient age, location, and severity or duration of relapse. Conclusions:1-6 Each relapse carries a risk of irreversible myelin and axonal loss determined by the extent and duration of the injury and inherent ability to recover. 7,8 Time to maximum recovery is believed to be associated with duration of pathogenic immunologic processes. 6 Early remyelination is likely important in determining the extent of recovery.Progressive disease course is characterized by insidious and irreversible accumulation of neurologic disability, with or without superimposed relapses or ongoing MRI activity.9-14 Patients with relapsing forms of MS often develop progressive MS.15 Secondary progressive MS (SPMS) †Deceased.