Impact of multiple sclerosis relapses on progression diminishes with time

Abstract

Objective:The relationship between relapses and long-term disability in multiple sclerosis (MS) remains to be fully elucidated. Current literature is conflicting and focused on early relapses. We investigated the effects of relapses at different stages on disability progression. Methods:We conducted a retrospective review of 2,477 patients with definite relapsing-onset MS followed until July 2003 in British Columbia, Canada. Time-dependent Cox proportional hazards models examined the effect of relapses at different time periods (0 -5; Ͼ5-10; Ͼ10 years postonset) on time to cane (Expanded Disability Status Scale [EDSS]) and secondary progressive MS (SPMS). Findings were derived from hazard ratios with 95% confidence intervals (CIs), adjusted for sex, onset age, and symptoms.Results: Mean follow-up was 20.6 years; 11,722 postonset relapses were recorded. An early relapse (within 5 years postonset) was associated with an increased hazard in disease progression over the short term, by 48%; 95% CI 37%-60% for EDSS 6 and 29%; 95% CI 20%-38% for SPMS. However, this substantially lessened to 10%; 95% CI 4%-16% (EDSS 6) and 2%; 95% CI Ϫ2%-7% (SPMS) after 10 years postonset. The impact of later relapses (Ͼ5-10 years postonset) also lessened over time. Effects were modulated by age, impact being greatest in younger (Ͻ25 years at onset) and least in older (Ն35 years) patients where relapses beyond 5-years postonset typically failed to reach significance. Relapses during SPMS had no measurable impact on time to EDSS 6 from SPMS. Conclusion:Relapses within the first 5 years of disease impacted on disease progression over the short term. However, the long-term impact was minimal, either for early or later relapses. Long-term disease progression was least affected by relapses in patients with an extended disease duration (Ͼ10 years) or already in the secondary progressive phase. Neurology Multiple sclerosis (MS) is a common cause of neurologic disability in young adults.1 The majority (85%) present with a relapsing-remitting (RR) course, with many later entering the secondary progressive (SP) phase. Disability accrual in MS is said to occur in 2 situations: incomplete recovery from a relapse or deterioration of functional ability outside of a relapse, synonymous with the progressive phase. 1The mechanisms involved in either relapses or irreversible disability are not fully understood. Relapses are associated with inflammation and demyelination; irreversible disability with axonal damage. However, destruction of axons and the myelin-oligodendrocyte complex occurs in early and late disease.

Relapses and disability accumulation in progressive multiple sclerosis

“…Several studies have documented no influence of superimposed relapses 9,22,23,[26][27][28] in SPMS or PPMS. Our findings conflict with these conclusions, but are consistent with a recent clinical trial.…”

Increased multiple sclerosis relapses related to lower prevalence of pain

“…One study 24 found that, in a long-term basis, accumulation of relapses and their consequences are less evident in patients with MS. Furthermore, with the advent of more powerful MRI scans, the confirmation of involvement of the gray matter became more sensitive.…”

Relapses do not matter in relation to long-term disability: No (they do)

“…That the subsequent time to more severe disability levels was found to be similar for those with or without relapses in these studies does not alter the fact that those with relapses developed disability at an earlier stage. This is best demonstrated in the analyses of Tremlett et al 10 They demonstrate that a higher relapse rate was associated with a shorter time to fixed disability (EDSS 6) and to onset of secondary progressive disease. They note that the effect of early relapses on the later development of disability diminishes with time.…”