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Open Access 17-09-2023 | Multiple Sclerosis | Original Communication

Multimodal MRI study on the relation between WM integrity and connected GM atrophy and its effect on disability in early multiple sclerosis

Authors: Merlin M. Weeda, D. R. van Nederpelt, J. W. R. Twisk, I. Brouwer, J. P. A. Kuijer, M. van Dam, H. E. Hulst, J. Killestein, F. Barkhof, H. Vrenken, P. J. W. Pouwels

Published in: Journal of Neurology | Issue 1/2024

Abstract

Background

Multiple sclerosis (MS) is characterized by pathology in white matter (WM) and atrophy of grey matter (GM), but it remains unclear how these processes are related, or how they influence clinical progression.

Objective

To study the spatial and temporal relationship between GM atrophy and damage in connected WM in relapsing–remitting (RR) MS in relation to clinical progression.

Methods

Healthy control (HC) and early RRMS subjects visited our center twice with a 1-year interval for MRI and clinical examinations, including the Expanded Disability Status Scale (EDSS) and Multiple Sclerosis Functional Composite (MSFC) scores. RRMS subjects were categorized as MSFC decliners or non-decliners based on ΔMSFC over time. Ten deep (D)GM and 62 cortical (C) GM structures were segmented and probabilistic tractography was performed to identify the connected WM. WM integrity was determined per tract with, amongst others, fractional anisotropy (FA), mean diffusivity (MD), neurite density index (NDI), and myelin water fraction (MWF). Linear mixed models (LMMs) were used to investigate GM and WM differences between HC and RRMS, and between MSFC decliners and non-decliners. LMM was also used to test associations between baseline WM z-scores and changes in connected GM z-scores, and between baseline GM z-scores and changes in connected WM z-scores, in HC/RRMS subjects and in MSFC decliners/non-decliners.

Results

We included 13 HCs and 31 RRMS subjects with an average disease duration of 3.5 years and a median EDSS of 3.0. Fifteen RRMS subjects showed declining MSFC scores over time, and they showed higher atrophy rates and greater WM integrity loss compared to non-decliners. Lower baseline WM integrity was associated with increased CGM atrophy over time in RRMS, but not in HC subjects. This effect was only seen in MSFC decliners, especially when an extended WM z-score was used, which included FA, MD, NDI and MWF. Baseline GM measures were not significantly related to WM integrity changes over time in any of the groups.

Discussion

Lower baseline WM integrity was related to more cortical atrophy in RRMS subjects that showed clinical progression over a 1-year follow-up, while baseline GM did not affect WM integrity changes over time. WM damage, therefore, seems to drive atrophy more than conversely.

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Title: Multimodal MRI study on the relation between WM integrity and connected GM atrophy and its effect on disability in early multiple sclerosis
Authors: Merlin M. Weeda
D. R. van Nederpelt
J. W. R. Twisk
I. Brouwer
J. P. A. Kuijer
M. van Dam
H. E. Hulst
J. Killestein
F. Barkhof
H. Vrenken
P. J. W. Pouwels
Publication date: 17-09-2023
Publisher: Springer Berlin Heidelberg
Keyword: Multiple Sclerosis
Published in: Journal of Neurology / Issue 1/2024
Print ISSN: 0340-5354
Electronic ISSN: 1432-1459
DOI: https://doi.org/10.1007/s00415-023-11937-2

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Multimodal MRI study on the relation between WM integrity and connected GM atrophy and its effect on disability in early multiple sclerosis

Abstract

Background

Objective

Methods

Results

Discussion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Objective

Methods

Results

Discussion

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