Gray matter atrophy patterns in multiple sclerosis: A 10-year source-based morphometry study

Abstract

Objectives: To investigate spatial patterns of gray matter (GM) atrophy and their association with disability progression in patients with early relapsing-remitting multiple sclerosis (MS) in a longitudinal setting.

Methods: Brain MRI and clinical neurological assessments were obtained in 152 MS patients at baseline and after 10 years of follow-up. Patients were classified into those with confirmed disability progression (CDP) (n = 85) and those without CDP (n = 67) at the end of the study. An optimized, longitudinal source-based morphometry (SBM) pipeline, which utilizes independent component analysis, was used to identify eight spatial patterns of common GM volume co-variation in a data-driven manner. GM volume at baseline and rates of change were compared between patients with CDP and those without CDP.

Results: The identified patterns generally included structurally or functionally related GM regions. No significant differences were detected at baseline GM volume between the sub-groups. Over the follow-up, patients with CDP experienced a significantly greater rate of GM atrophy within two of the eight patterns, after correction for multiple comparisons (corrected p-values of 0.001 and 0.007). The patterns of GM atrophy associated with the development of CDP included areas involved in motor functioning and cognitive domains such as learning and memory.

Conclusion: SBM analysis offers a novel way to study the temporal evolution of regional GM atrophy. Over 10 years of follow-up, disability progression in MS is related to GM atrophy in areas associated with motor and cognitive functioning.

Keywords: Atrophy; Disability; Gray matter; MRI; Multiple sclerosis.

Fig. 1

Source-based morphometry results showing the eight patterns of gray matter volume that were identified in all 152 multiple sclerosis patients at baseline and ten years of follow-up. Z-scores, thresholded at | 3 |, are shown in red-yellow for each component, with yellow being associated with larger values. Although no differences were identified at baseline, patients with confirmed disability progression (CDP) after ten years of follow-up had a significantly greater rate of atrophy in Patterns 1 and 7 compared to those without CDP, after correction for multiple comparisons. The X, Y and Z values refer to the slice shown in Montreal Neurological Institute coordinates.

Fig. 2

Source-based morphometry results showing the eight patterns of gray matter (GM) volume that were identified in all 152 multiple sclerosis patients and 31 healthy controls at baseline. Z-scores, thresholded at | 3 |, are shown in red-yellow for each component, with yellow being associated with larger values. Compared to healthy controls, multiple sclerosis patients had significantly reduced GM volume in Patterns 1 and 7 after correction for multiple comparisons. The X, Y and Z values refer to the slice shown in Montreal Neurological Institute coordinates.

Supplementary Fig. 1

Voxel-based morphometry results comparing gray matter differences between multiple sclerosis patients and healthy controls at baseline. Areas of significantly decreased gray matter volume are shown in red-yellow, with yellow being associated with smaller p-values. Effects related to age, sex, and head size were regressed out from the analyses and results are shown with threshold-free cluster enhancement at p < 0.05, family-wise error corrected. The X, Y and Z values refer to the slice shown in Montreal Neurological Institute coordinates.

Supplementary Fig. 2

Voxel-based morphometry results comparing gray matter atrophy in patients with confirmed disability progression (CDP) and those without after ten years of follow-up. Areas with a significantly greater rate of gray matter loss are shown in red-yellow, with yellow being associated with smaller p-values. Effects related to age, sex, and head size were regressed out from the analyses and results are shown with threshold-free cluster enhancement at p < 0.05, family-wise error corrected. The X, Y and Z values refer to the slice shown in Montreal Neurological Institute coordinates.