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Relationship between brain white matter damage and grey matter atrophy in hereditary spastic paraplegia types 4 and 5
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Relationship between brain white matter damage and grey matter atrophy in hereditary spastic paraplegia types 4 and 5
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Journal Article
Relationship between brain white matter damage and grey matter atrophy in hereditary spastic paraplegia types 4 and 5
2024
Overview
Background and purpose White matter (WM) damage is the main target of hereditary spastic paraplegia (HSP), but mounting evidence indicates that genotype‐specific grey matter (GM) damage is not uncommon. Our aim was to identify and compare brain GM and WM damage patterns in HSP subtypes and investigate how gene expression contributes to these patterns, and explore the relationship between GM and WM damage. Methods In this prospective single‐centre cohort study from 2019 to 2022, HSP patients and controls underwent magnetic resonance imaging evaluations. The alterations of GM and WM patterns were compared between groups by applying a source‐based morphometry approach. Spearman rank correlation was used to explore the associations between gene expression and GM atrophy patterns in HSP subtypes. Mediation analysis was conducted to investigate the interplay between GM and WM damage. Results Twenty‐one spastic paraplegia type 4 (SPG4) patients (mean age 50.7 years ± 12.0 SD, 15 men), 21 spastic paraplegia type 5 (SPG5) patients (mean age 29.1 years ± 12.8 SD, 14 men) and 42 controls (sex‐ and age‐matched) were evaluated. Compared to controls, SPG4 and SPG5 showed similar WM damage but different GM atrophy patterns. GM atrophy patterns in SPG4 and SPG5 were correlated with corresponding gene expression (ρ = 0.30, p = 0.008, ρ = 0.40, p < 0.001, respectively). Mediation analysis indicated that GM atrophy patterns were mediated by WM damage in HSP. Conclusions Grey matter atrophy patterns were distinct between SPG4 and SPG5 and were not only secondary to WM damage but also associated with disease‐related gene expression. Clinical trial registration no. NCT04006418.
Publisher
John Wiley & Sons, Inc
Subject
/ Atrophy
/ Female
/ Gray Matter - diagnostic imaging
/ Hereditary spastic paraplegia
/ Humans
/ Male
/ spastic paraplegia, hereditary
/ Spastic Paraplegia, Hereditary - diagnostic imaging
/ Spastic Paraplegia, Hereditary - genetics
/ Spastic Paraplegia, Hereditary - pathology
