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

Weeda, Merlin M; van Nederpelt, DR; Twisk, JWR; Brouwer, I; Kuijer, JPA; van Dam, M; Hulst, HE; ... Pouwels, PJW; + view all (2023) Multimodal MRI study on the relation between WM integrity and connected GM atrophy and its effect on disability in early multiple sclerosis. Journal of Neurology 10.1007/s00415-023-11937-2.

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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.

Type: Article
Title: Multimodal MRI study on the relation between WM integrity and connected GM atrophy and its effect on disability in early multiple sclerosis
Location: Germany
DOI: 10.1007/s00415-023-11937-2
Publisher version: https://doi.org/10.1007/s00415-023-11937-2
Language: English
Additional information: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
Keywords: Atrophy, Connectivity, MRI, Multiple sclerosis, White matter damage
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Brain Repair and Rehabilitation
URI: https://discovery.ucl.ac.uk/id/eprint/10176964
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