Evolution of Chronic Lesion Tissue in Relapsing-Remitting Patients With Multiple Sclerosis: An Association With Disease Progression

Abstract

In this study, we examine the long-term changes in chronic lesion tissue (CLT) among patients with relapsing-remitting MS (RRMS), focusing on its impact on clinical and radiologic disease progression indicators. The study involved 72 patients with multiple sclerosis with at least a 5-year follow-up. Annual assessments used 3D fluid-attenuated inversion recovery (FLAIR), precontrast and postcontrast 3D T1, and diffusion-weighted MRI. Lesion segmentation was conducted using iQ-MS software, while brain structures were segmented using AssemblyNet. Volumetric changes in CLT were tracked using a novel custom-designed pipeline that estimates longitudinal volumetric changes in CLT using serial MRI data. Throughout the follow-up period, the volume of CLT in the entire cohort increased continuously and steadily, averaging 7.75% ± 8.2% or 315 ± 465 mm³ per year. Patients with expanding CLT experienced significantly faster brain atrophy, affecting both white and gray matter, particularly in the brain's central area. Expanded CLT was also associated with higher and worsening Expanded Disability Status Scale (EDSS) scores, in contrast to the stable CLT group, where EDSS remained unchanged. Sample size calculation for a clinical trial investigating the effect of treatment on slow expansion of chronic lesions demonstrated that a relatively small cohort of patients with RRMS, ranging from 24 to 69 patients per arm, would be required. This study demonstrates that, over a period of up to 5 years, patient-specific enlargement of CLT, when present, progresses at a constant rate and significantly influences brain atrophy and disease progression. In addition, the study underscores CLT as a promising biomarker for RRMS progression and suggests the feasibility of smaller, targeted clinical trials to evaluate treatments aimed at reducing chronic lesion expansion.