A 30-Year Clinical and Magnetic Resonance Imaging Observational Study of Multiple Sclerosis and Clinically Isolated Syndromes

Abstract

Objective: Clinical outcomes in multiple sclerosis (MS) are highly variable. We aim to determine the long-term clinical outcomes in MS, and to identify early prognostic features of these outcomes.

Methods: One hundred thirty-two people presenting with a clinically isolated syndrome were prospectively recruited between 1984 and 1987, and followed up clinically and radiologically 1, 5, 10, 14, 20, and now 30 years later. All available notes and magnetic resonance imaging scans were reviewed, and MS was defined according to the 2010 McDonald criteria.

Results: Clinical outcome data were obtained in 120 participants at 30 years. Eighty were known to have developed MS by 30 years. Expanded Disability Status Scale (EDSS) scores were available in 107 participants, of whom 77 had MS; 32 (42%) remained fully ambulatory (EDSS scores ≤3.5), all of whom had relapsing-remitting MS (RRMS), 3 (4%) had RRMS and EDSS scores >3.5, 26 (34%) had secondary progressive MS (all had EDSS scores >3.5), and MS contributed to death in 16 (20%). Of those with MS, 11 received disease-modifying therapy. The strongest early predictors (within 5 years of presentation) of secondary progressive MS at 30 years were presence of baseline infratentorial lesions and deep white matter lesions at 1 year.

Interpretation: Thirty years after onset, in a largely untreated cohort, there was a divergence of MS outcomes; some people accrued substantial disability early on, whereas others ran a more favorable long-term course. These outcomes could, in part, be predicted by radiological findings from within 1 year of first presentation. ANN NEUROL 2020;87:63-74.

Figure 1

Representative axial brain images from 1 participant, acquired at baseline (A), 5 years (B), 10 years (C), 14 years (D), 20 years (E), and 30 years (F). At baseline and 5 years only proton‐density–weighted images were acquired, whereas at later time points T2‐weighted images were acquired and are shown. Please refer to the main text for a description of the scan acquisition parameters at each time point.

Figure 2

Expanded Disability Status Scale (EDSS) scores at 30 years. EDSS scores were obtained from 107 individuals at 30 years. An EDSS score of 10 was only assigned to those where multiple sclerosis (MS) was known to have contributed to death. In the 3 other people with MS who had died, the cause of death was either unrelated to MS or unknown, and no EDSS score was assigned. CIS = clinically isolated syndrome; RRMS = relapsing–remitting multiple sclerosis; SPMS = secondary progressive multiple sclerosis.

Figure 3

Employment and retirement status in people with multiple sclerosis, by the Expanded Disability Status Scale at 30 years (n = 61). FT = full time; PT = part time.

Figure 4

Expanded Disability Status Scale (EDSS) trajectories over 30 years by 30‐year status. CIS = clinically isolated syndrome; MS = multiple sclerosis; RRMS = relapsing–remitting multiple sclerosis; SPMS = secondary progressive multiple sclerosis.