Thalamic Atrophy in MS: An MRI Marker of Neurodegeneration Throughout Disease

ABSTRACT

Objective: Thalamic volume is a candidate MRI-based marker associated with neurodegeneration to hasten development of neuroprotective treatments. Our objective is to describe the longitudinal evolution of thalamic atrophy in MS and normal aging, and to estimate sample sizes for study design.

Methods: 601 subjects (2632 MRI scans) were analyzed. 520 subjects with relapse-onset MS [CIS(90); RR(392); SP(38)] underwent annual standardized 3T MRI scans for an average of 4.1 years, including a 1mm³ 3D T1-weighted sequence (3DT1; 2485 MRI scans). 81 healthy controls (HC) were scanned longitudinally on the same scanner using the same protocol (147 MRI scans). 3DT1s were processed using FreeSurfer's longitudinal pipeline after lesion inpainting. Rates of normalized thalamic volume loss in MS and HC were compared in linear mixed effects models. Simulation-based sample size calculations were performed incorporating the rate of atrophy in HC.

Results: Thalamic volume declined significantly faster in MS subjects compared to HC, with an estimated decline of -0.71% per year (95% CI -0.77%, -0.64%) in MS subjects and -0.28% per year (95% CI -0.58%, 0.02%) in HC (p-value for difference=0.007). The rate of decline was consistent throughout the MS disease duration and across MS clinical subtypes. 80 or 100 subjects per arm (α=0.1 or 0.05, respectively) would be needed to detect the 'maximal effect size' with 80% power in a 24-month study.

Interpretation: Thalamic atrophy occurs early and consistently throughout MS. Preliminary sample size calculations appear feasible, adding to its appeal as an MRI marker associated with neurodegeneration. This article is protected by copyright. All rights reserved.

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