Annals of clinical and translational neurology · 2026
Normal-Appearing White Matter Injury Mediates Chronic Deep Venous Hypoxia and Disease Progression in Multiple Sclerosis.
СтатьяНаблюдательное исследованиеНазвание и аннотация: Перевод в очереди
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Wang Xinli, Wang Huiying, Zhuo Zhizheng, Guo Ai, Lv Ke, Tian Decai, Chai Chao, Duan Yunyun, Xia Shuang
Аннотация
OBJECTIVE: To explore how cerebral hypoxia and Normal-Appearing White Matter (NAWM) integrity affect MS lesion burden and clinical course.
METHODS: Seventy-nine MS patients, including 13 clinically isolated syndrome (CIS) patients and 66 relapsing-remitting multiple sclerosis (RRMS) patients, and 44 healthy controls (HCs) were recruited from CLUE, NCT04106830. Quantitative susceptibility mapping (QSM) was employed to evaluate the changes of cerebral venous oxygen saturation (SvO2) in deep cerebral veins. Diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging analyzes (NODDI) were employed to evaluate microstructural alterations in deep brain white matter (WM), including WM lesion and NAWM between MS and HCs. Partial correlations analyzes were conducted to examine associations between imaging biomarkers and clinical indicators. Mediation analysis was used to evaluate the relationship among SvO2, microstructural alterations, lesion volumes, and clinical indicators.
RESULTS: Compared with HCs, patients with MS showed significantly decreased SvO2 in the internal cerebral vein (76.56% ± 1.34% vs. 78.80% ± 0.86%, p < 0.001). Advanced diffusion metrics revealed extensive microstructural disruption in both WM lesions and NAWM (NAWM mean diffusivity [MD]: 1.03 ± 0.12 vs. 0.90 ± 0.04 [×10-3 mm2/s], p < 0.001). Furthermore, microstructural disruption of NAWM (MD and orientation dispersion index [ODI]) significantly correlated with SvO2 of the ICV (MD: r = -0.307, p = 0.036; ODI: r = -0.279, p = 0.036). Critically, mediation analysis demonstrated that deep brain WM hypoxia (ICV SvO2) associated with greater lesion burden and clinical disability via NAWM damage as an intermediate pathway.
INTERPRETATION: In MS patients, lower cerebral SvO2 (compared with HCs) is statistically associated with microstructural alterations in the NAWM. Our mediation models are consistent with a pathway whereby lower SvO2 is associated with greater lesion burden and worse functional scores via its association with NAWM damage. These findings support the exploratory value of SvO2 and NAWM integrity as potential biomarkers for monitoring MS progression, which warrants validation in further longitudinal studies.
METHODS: Seventy-nine MS patients, including 13 clinically isolated syndrome (CIS) patients and 66 relapsing-remitting multiple sclerosis (RRMS) patients, and 44 healthy controls (HCs) were recruited from CLUE, NCT04106830. Quantitative susceptibility mapping (QSM) was employed to evaluate the changes of cerebral venous oxygen saturation (SvO2) in deep cerebral veins. Diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging analyzes (NODDI) were employed to evaluate microstructural alterations in deep brain white matter (WM), including WM lesion and NAWM between MS and HCs. Partial correlations analyzes were conducted to examine associations between imaging biomarkers and clinical indicators. Mediation analysis was used to evaluate the relationship among SvO2, microstructural alterations, lesion volumes, and clinical indicators.
RESULTS: Compared with HCs, patients with MS showed significantly decreased SvO2 in the internal cerebral vein (76.56% ± 1.34% vs. 78.80% ± 0.86%, p < 0.001). Advanced diffusion metrics revealed extensive microstructural disruption in both WM lesions and NAWM (NAWM mean diffusivity [MD]: 1.03 ± 0.12 vs. 0.90 ± 0.04 [×10-3 mm2/s], p < 0.001). Furthermore, microstructural disruption of NAWM (MD and orientation dispersion index [ODI]) significantly correlated with SvO2 of the ICV (MD: r = -0.307, p = 0.036; ODI: r = -0.279, p = 0.036). Critically, mediation analysis demonstrated that deep brain WM hypoxia (ICV SvO2) associated with greater lesion burden and clinical disability via NAWM damage as an intermediate pathway.
INTERPRETATION: In MS patients, lower cerebral SvO2 (compared with HCs) is statistically associated with microstructural alterations in the NAWM. Our mediation models are consistent with a pathway whereby lower SvO2 is associated with greater lesion burden and worse functional scores via its association with NAWM damage. These findings support the exploratory value of SvO2 and NAWM integrity as potential biomarkers for monitoring MS progression, which warrants validation in further longitudinal studies.