Abstract
ObjectivesTo compare clinical and MRI parameters between patients with clinically isolated syndrome and those converting to clinically definite multiple sclerosis within 2 years, to identify volumetric MRI predictors of this conversion and to assess effect of early relapses.MethodsThe SET study comprised 220 patients with clinically isolated syndrome treated with interferon beta (mean age, 29 years; Expanded Disability Status Scale, 1.5). Three patients with missing data were excluded from the analysis. Physical disability, time to clinically definite multiple sclerosis and volumetric MRI data were recorded for 2 years.ResultsPatients reaching clinically definite multiple sclerosis showed impaired recovery of neurological function, faster decrease in corpus callosum cross-sectional area, higher T2 lesion volume and more contrast-enhancing lesions. Six-month decrease in corpus callosum cross-sectional area (≥1%) and baseline T2 lesion volume (≥5 cm3) predicted clinically definite multiple sclerosis within 2 years (hazard ratios 2.5 and 1.8, respectively). Of 22 patients fulfilling both predictive criteria, 83% reached clinically definite multiple sclerosis (hazard ratio 6.5). More relapses were associated with poorer recovery of neurological function and accelerated brain atrophy.ConclusionsNeurological impairment is more permanent, brain atrophy is accelerated and focal inflammatory activity is greater in patients converting to clinically definite multiple sclerosis. Six-month corpus callosum atrophy and baseline T2 lesion volume jointly help predict individual risk of clinically definite multiple sclerosis. Early relapses contribute to permanent damage of the central nervous system.
Highlights
Of the 217 patients included in this analysis, 92 (42%) converted to clinically definite multiple sclerosis (CDMS) during the 2 years from the initial demyelinating event
Both Expanded Disability Status Scale (EDSS) and Multiple Sclerosis Functional Composite (MSFC) indicated that neurological function recovered to a greater extent in the clinically isolated syndrome (CIS) than the CDMS group (p = 1025 and 0.05, respectively, mixed model)
While relative changes in whole brain, white matter (WM) and grey matter (GM) volumes showed consistent trends to decrease faster in the CDMS group, these trends did not reach the level of statistical significance (p.0.1, mixed models)
Summary
One half of patients with clinically isolated syndrome (CIS) develop clinically definite multiple sclerosis (CDMS) within the initial 5 years of the first clinical relapse and this proportion grows to two thirds at 20 years.[1,2,3,4] It has been shown that disease modifying therapy has the potential to delay a second demyelinating event and decrease the CDMS conversion rate. [5] early identification of patients at high risk of ongoing relapsing activity is crucial for timely treatment escalation.Structural changes within the central nervous system (CNS) occur early in multiple sclerosis (MS) course. [6] Abnormal brain MRI at the time of CIS is associated with increased risk of further relapses, i.e. of CDMS conversion. [7,8] Both localised inflammatory changes and the rate of brain atrophy can predict risk of ongoing relapsing activity. [2,4]Here we report outcomes of the 2-year analysis of longitudinal quantitative MRI data from the SET study (Study of Early Interferon b1-a Treatment in High Risk Subjects after CIS). One half of patients with clinically isolated syndrome (CIS) develop clinically definite multiple sclerosis (CDMS) within the initial 5 years of the first clinical relapse and this proportion grows to two thirds at 20 years.[1,2,3,4] It has been shown that disease modifying therapy has the potential to delay a second demyelinating event and decrease the CDMS conversion rate. [5] early identification of patients at high risk of ongoing relapsing activity is crucial for timely treatment escalation. [6] Abnormal brain MRI at the time of CIS is associated with increased risk of further relapses, i.e. of CDMS conversion. [7,8] Both localised inflammatory changes and the rate of brain atrophy can predict risk of ongoing relapsing activity. Our aims were (i) to compare clinical and MRI changes between patients with CIS and those converting to CDMS, (ii) to identify early MRI predictors of CDMS conversion and (iii) to evaluate the effect of relapses on clinical and MRI parameters
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