Abstract

Disappearance of T2 lesions into CSF spaces is frequently observed in patients with MS. Our aim was to investigate temporal changes of cumulative atrophied brain T2 lesion volume and 10-year confirmed disability progression. We studied 176 patients with relapsing-remitting MS who underwent MR imaging at baseline, 6 months, and then yearly for 10 years. Occurrence of new/enlarging T2 lesions, changes in T2 lesion volume, and whole-brain, cortical and ventricle volumes were assessed yearly between baseline and 10 years. Atrophied T2 lesion volume was calculated by combining baseline lesion masks with follow-up CSF partial volume maps. Ten-year confirmed disability progression was confirmed after 48 weeks. ANCOVA detected MR imaging outcome differences in stable (n = 76) and confirmed disability progression (n = 100) groups at different time points; hierarchic regression determined the unique additive variance explained by atrophied T2 lesion volume regarding the association with confirmed disability progression, in addition to other MR imaging metrics. Cox regression investigated the association of early MR imaging outcome changes and time to development of confirmed disability progression. The separation of stable-versus-confirmed disability progression groups became significant even in the first 6 months for atrophied T2 lesion volume (140% difference, Cohen d = 0.54, P = .004) and remained significant across all time points (P ≤ .007). The hierarchic model, including all other MR imaging outcomes during 10 years predicting confirmed disability progression, improved significantly after adding atrophied T2 lesion volume (R 2 = 0.27, R 2 change 0.11, P = .009). In Cox regression, atrophied T2 lesion volume in 0-6 months (hazard ratio = 4.23, P = .04) and 0-12 months (hazard ratio = 2.41, P = .022) was the only significant MR imaging predictor of time to confirmed disability progression. Atrophied T2 lesion volume is a robust and early marker of disability progression in relapsing-remitting MS.

Highlights

  • BACKGROUND AND PURPOSEDisappearance of T2 lesions into CSF spaces is frequently observed in patients with MS

  • Appearance or accumulation of new or enlarging brain lesions or changes in lesion volume (LV) on MR imaging have been used as primary end points in Phase II clinical trials and as secondary end points in Phase III trials in multiple sclerosis.[1,2,3]

  • We aimed to investigate temporal changes of atrophied T2-LV and disease progression, using a well-established cohort of patients with early RRMS who participated in a previous clinical trial,[16] and its long-term open-label 10-year extension,[8,17,18] using serial MR imaging

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Summary

Objectives

Our aim was to investigate temporal changes of cumulative atrophied brain T2 lesion volume and 10-year confirmed disability progression. We aimed to investigate temporal changes of atrophied T2-LV and disease progression, using a well-established cohort of patients with early RRMS who participated in a previous clinical trial, and its long-term open-label 10-year extension, using serial MR imaging

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