Temporal Dynamics of Diffusion Metrics in Early Multiple Sclerosis and Clinically Isolated Syndrome: A 2-Year Follow-Up Tract-Based Spatial Statistics Study.

Ruth Schneider,Erhan Genç,Christian Ahlborn,Carsten Lukas,Ralf Gold,Barbara Bellenberg

doi:10.3389/fneur.2019.01165

Ruth Schneider, Erhan Genç + Show 4 more

Open Access

https://doi.org/10.3389/fneur.2019.01165

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Abstract

Background: Tract-based spatial statistics (TBSS) is suitable for the assessment of voxel-wise changes in fiber integrity in WM tracts in the entire brain. Longitudinal TBSS analyses of early multiple sclerosis (MS) using 3 Tesla magnetic resonance imaging (MRI) are not common.Objective: To characterize microstructural WM alterations at initial diagnosis in clinically isolated syndrome (CIS) and early MS at baseline and longitudinally over 2 years.Methods: DTI (Diffusion tensor imaging) at 3 Tesla was used to evaluate 106 therapy-naive patients with CIS or definite MS at baseline and at 1-year (N = 83) and 2-year (N = 43) follow-up compared to healthy controls (HC, N = 49). TBSS was used for voxel-wise analyses of the DTI indices of fractional anisotropy (FA) and radial, mean, and axial diffusivity (RD, MD, AD) for cross-sectional and longitudinal comparisons. Mean values of FA, RD, and cluster voxel numbers were extracted from significant clusters using an atlas-based approach. Correlations with disability (EDSS) were calculated for FA and RD changes related to affected brain regions.Results: Reductions in FA compared to HC were found at baseline in patients with CIS and RRMS and involved most supra- and infratentorial WM tracts. In the cerebellum and cerebral peduncles, these changes negatively correlated with EDSS after 2 years. FA changes in patients with CIS and RRMS evolved in the second year, particularly in the descending projection pathways and the cerebellum, and were significantly associated with EDSS. RD alterations compared to HC were undetectable in patients at baseline but were observed after 1 year and were exacerbated during the second year in all major supratentorial WM tracts, the corpus callosum, and the cerebellum. FA did not change between baseline and year 1 follow-up, but longitudinal investigation between the first and second year revealed combined dynamic FA and RD changes in the corpus callosum and corona radiata.Conclusion: TBSS of diffusion metrics at initial diagnosis and at 2-year follow-up showed microstructural WM pathology and associations between FA reduction and future disability, respectively. Combined longitudinal changes in FA and RD occurred in specific structures, where RD increases likely reflected progressing axonal degeneration. The distinct temporal dynamics of FA and RD, implying constancy during the first year, supports early therapeutic intervention for CIS and RRMS.

Highlights

Multiple sclerosis (MS) is a chronic disease of the central nervous system (CNS) characterized by demyelination and axonal injury
Voxel-Wise diffusion tensor imaging (DTI) Analysis Voxel-wise Tract-based spatial statistics (TBSS) analysis showed local clusters of significantly reduced fractional anisotropy (FA) in patients compared to controls at baseline and at FU1, with FA reduced further at FU2 throughout most of the major brain white matter tracts, including the cerebellum (Figure 1, left row, red overlay)
Our results agreed with recent observations of marked FA reductions in brain white matter (WM) tracts in patients with CIS and more widespread disturbances in DTI metrics in patients with longstanding RRMS compared with patients with CIS [1, 3]

Summary

Introduction

Multiple sclerosis (MS) is a chronic disease of the central nervous system (CNS) characterized by demyelination and axonal injury. Conventional magnetic resonance imaging (MRI) is a very sensitive technique for detecting focal MS-related macroscopic lesions but suffers from a lack of histopathological specificity. Several MRI studies using non-conventional MRI techniques such as DTI have confirmed that MS-related damage affects white matter (WM) at the microscopic level [1]. Evaluation of microstructural changes in the brain beyond the locations of MS lesions using MRI techniques has become critical for the evaluation of early MS [2,3,4]. Radial diffusivity (RD) and axial diffusivity (AD), which are additional DTI metrics, have been suggested as markers of myelin and axonal damage, respectively [6]. Longitudinal TBSS analyses of early multiple sclerosis (MS) using 3 Tesla magnetic resonance imaging (MRI) are not common

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