Glymphatic dysfunction in moyamoya disease: The influence of arterial stenosis and ventricular enlargement

The glymphatic system is a vascular-dependent network, involving cerebrospinal fluid circulation, that facilitates waste clearance from the brain. Although glymphatic dysfunction has been implicated in various neurologic diseases, its influencing factors are still not fully understood. We aimed to e...

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Main Authors: Duo Xu, Linglin Yang, Biao Jiang, Xinfeng Yu
Format: Article
Language:English
Published: Elsevier 2025-04-01
Series:NeuroImage
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Online Access:http://www.sciencedirect.com/science/article/pii/S1053811925001454
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author Duo Xu
Linglin Yang
Biao Jiang
Xinfeng Yu
author_facet Duo Xu
Linglin Yang
Biao Jiang
Xinfeng Yu
author_sort Duo Xu
collection DOAJ
description The glymphatic system is a vascular-dependent network, involving cerebrospinal fluid circulation, that facilitates waste clearance from the brain. Although glymphatic dysfunction has been implicated in various neurologic diseases, its influencing factors are still not fully understood. We aimed to evaluate glymphatic clearance in moyamoya disease (MMD) and explore its associations with arterial stenosis and ventricular size. Patients with MMD and healthy controls were prospectively recruited to undergo multi-modal MRI scans. Patients were divided into three subgroups based on initial symptoms: hemorrhagic, ischemic, and other. We used diffusion tensor image analysis along the perivascular space (DTI-ALPS) index, magnetic resonance angiography, 3D T1-weighted images to evaluate glymphatic clearance, arterial stenosis and ventricular size. The relationships between arterial stenosis, ventricular size, and ALPS index were analyzed using multivariable linear regression analyses. Compared to controls (n = 39), patients (n = 55) exhibited reduced ALPS index (p < 0.001) and increased volumes of the lateral ventricles (p < 0.001), third ventricle (p < 0.001) and fourth ventricle (p = 0.013). In MMD, arterial stenosis (standardized β=-0.283, p = 0.013), lateral ventricular volume (standardized β=-0.504, p < 0.001), and their interaction (standardized β=-0.606, p < 0.001) were all significantly associated with the ALPS index in multivariable analysis. Among the three subgroups, hemorrhagic subgroup had the lowest ALPS index (p = 0.085) and the largest lateral ventricular volume (p = 0.013). Our findings demonstrated that enlarged lateral ventricles were associated with decreased ALPS index, both alone and synergistically with arterial stenosis, and the reduced ALPS index and ventricular enlargement would be exacerbated in hemorrhagic MMD. This evidence provides new insights into the mechanisms underlying glymphatic impairment in MMD.
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spelling doaj-art-1c9a8a43eccc4cd3b5a9bfc4eeec3d7f2025-08-20T03:17:54ZengElsevierNeuroImage1095-95722025-04-0131012114310.1016/j.neuroimage.2025.121143Glymphatic dysfunction in moyamoya disease: The influence of arterial stenosis and ventricular enlargementDuo Xu0Linglin Yang1Biao Jiang2Xinfeng Yu3Department of Radiology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, PR ChinaDepartment of Psychiatry, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, PR ChinaDepartment of Radiology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, PR ChinaDepartment of Radiology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, PR China; Corresponding author: Department of Radiology, The Second Affiliated Hospital of Zhejiang University, School of Medicine, No.88 Jiefang Road, Shangcheng District, Hangzhou, Zhejiang 310009, PR China.The glymphatic system is a vascular-dependent network, involving cerebrospinal fluid circulation, that facilitates waste clearance from the brain. Although glymphatic dysfunction has been implicated in various neurologic diseases, its influencing factors are still not fully understood. We aimed to evaluate glymphatic clearance in moyamoya disease (MMD) and explore its associations with arterial stenosis and ventricular size. Patients with MMD and healthy controls were prospectively recruited to undergo multi-modal MRI scans. Patients were divided into three subgroups based on initial symptoms: hemorrhagic, ischemic, and other. We used diffusion tensor image analysis along the perivascular space (DTI-ALPS) index, magnetic resonance angiography, 3D T1-weighted images to evaluate glymphatic clearance, arterial stenosis and ventricular size. The relationships between arterial stenosis, ventricular size, and ALPS index were analyzed using multivariable linear regression analyses. Compared to controls (n = 39), patients (n = 55) exhibited reduced ALPS index (p < 0.001) and increased volumes of the lateral ventricles (p < 0.001), third ventricle (p < 0.001) and fourth ventricle (p = 0.013). In MMD, arterial stenosis (standardized β=-0.283, p = 0.013), lateral ventricular volume (standardized β=-0.504, p < 0.001), and their interaction (standardized β=-0.606, p < 0.001) were all significantly associated with the ALPS index in multivariable analysis. Among the three subgroups, hemorrhagic subgroup had the lowest ALPS index (p = 0.085) and the largest lateral ventricular volume (p = 0.013). Our findings demonstrated that enlarged lateral ventricles were associated with decreased ALPS index, both alone and synergistically with arterial stenosis, and the reduced ALPS index and ventricular enlargement would be exacerbated in hemorrhagic MMD. This evidence provides new insights into the mechanisms underlying glymphatic impairment in MMD.http://www.sciencedirect.com/science/article/pii/S1053811925001454Moyamoya diseaseGlymphatic systemMagnetic resonance imagingDiffusion tensor imageCerebral ventricles
spellingShingle Duo Xu
Linglin Yang
Biao Jiang
Xinfeng Yu
Glymphatic dysfunction in moyamoya disease: The influence of arterial stenosis and ventricular enlargement
NeuroImage
Moyamoya disease
Glymphatic system
Magnetic resonance imaging
Diffusion tensor image
Cerebral ventricles
title Glymphatic dysfunction in moyamoya disease: The influence of arterial stenosis and ventricular enlargement
title_full Glymphatic dysfunction in moyamoya disease: The influence of arterial stenosis and ventricular enlargement
title_fullStr Glymphatic dysfunction in moyamoya disease: The influence of arterial stenosis and ventricular enlargement
title_full_unstemmed Glymphatic dysfunction in moyamoya disease: The influence of arterial stenosis and ventricular enlargement
title_short Glymphatic dysfunction in moyamoya disease: The influence of arterial stenosis and ventricular enlargement
title_sort glymphatic dysfunction in moyamoya disease the influence of arterial stenosis and ventricular enlargement
topic Moyamoya disease
Glymphatic system
Magnetic resonance imaging
Diffusion tensor image
Cerebral ventricles
url http://www.sciencedirect.com/science/article/pii/S1053811925001454
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AT biaojiang glymphaticdysfunctioninmoyamoyadiseasetheinfluenceofarterialstenosisandventricularenlargement
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