Glymphatic system impairment in Wilson’s disease: An overlooked mechanism for neurological dysfunction?

IF 5.3 2区医学 Q1 NEUROIMAGING

NeuroImage Pub Date : 2026-03-01 Epub Date: 2026-02-13 DOI:10.1016/j.neuroimage.2026.121792

Gaiying Li , Siyuan Fang , Yupeng Wu , Xiangzhen Yuan , Ying Tang , Xiaozhong Jing , Luguang Chen , Xiaoping Wang , Jianqi Li

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引用次数: 0

Abstract

Background

Mounting evidence highlights the critical role of the brain’s glymphatic system in cerebral waste clearance, yet its alterations in Wilson’s disease (WD) remain unclear. This study aimed to systematically evaluate structural and functional alterations of the glymphatic system across WD clinical phenotypes and their associations with neurological impairment.

Methods

Nineteen patients with neurological WD (neuro-WD), 13 with hepatic WD (hep-WD), and 25 healthy controls (HCs) were enrolled. Quantitative MRI metrics included choroid plexus (ChP) volume and diffusion parameters, basal ganglia perivascular space (PVS_BG) volume, and free water-eliminated diffusion tensor imaging analysis along the perivascular space (FWE-DTI-ALPS) index. Group differences were analyzed using ANCOVA, post hoc t-tests, and receiver operating characteristic analyses. Partial correlation analyses were performed to examine associations between MRI and clinical parameters.

Results

ChP and PVS_BG volumes increased progressively across HC, hep-WD, and neuro-WD groups, whereas the FWE-DTI-ALPS index decreased (all p < 0.01), accompanied by elevated free water content and altered diffusion properties in the ChP. The combination of ChP and PVS markers distinguished WD from HC (AUC = 0.939), while ChP volume alone effectively differentiated neuro-WD from hep-WD (AUC = 0.799). ChP volume correlated negatively with the FWE-DTI-ALPS index (r = –0.619), and PVS_BG volume was inversely associated with FWE-DTI-ALPS (r = –0.320). Clinically, ChP enlargement correlated with higher urinary copper levels, whereas fractional anisotropy values, both before and after free water correction, were negatively correlated with serum iron.

Conclusions

These findings provide preliminary imaging evidence of alterations in glymphatic-related MRI markers in WD and suggest that these markers may help differentiate neurological from hepatic phenotypes in research settings. In addition, we emphasize that the observed ALPS changes should be interpreted cautiously, and future longitudinal and multi-shell studies are required before clinical translation can be considered.

查看原文本刊更多论文

威尔逊病的淋巴系统损伤：一种被忽视的神经功能障碍机制？

背景：越来越多的证据强调了脑淋巴系统在脑废物清除中的关键作用，但其在威尔逊病（WD）中的改变尚不清楚。本研究旨在系统地评估跨WD临床表型的淋巴系统的结构和功能改变及其与神经损伤的关系。方法：选取19例神经性WD （neurod -WD）患者、13例肝脏WD （hep-WD）患者和25例健康对照（hc）。定量MRI指标包括脉络膜丛（ChP）体积和扩散参数、基底节区血管周围空间（PVSBG）体积、沿血管周围空间自由消水扩散张量成像分析（FWE-DTI-ALPS）指数。采用ANCOVA、事后t检验和受试者工作特征分析分析组间差异。进行偏相关分析以检查MRI与临床参数之间的关联。结果：ChP和PVSBG体积在HC、hep-WD和neurod组逐渐增加，而FWE-DTI-ALPS指数下降(所有p BG体积与FWE-DTI-ALPS呈负相关（r = -0.320）。临床上，ChP增大与尿铜水平升高相关，而自由水校正前后各向异性分数值与血清铁呈负相关。结论：这些发现提供了WD中淋巴相关MRI标记物改变的初步影像学证据，并提示这些标记物可能有助于在研究环境中区分神经表型和肝脏表型。此外，我们强调观察到的ALPS变化应谨慎解释，在考虑临床翻译之前，需要进行未来的纵向和多壳研究。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

NeuroImage 医学-核医学

CiteScore

11.30

自引率

10.50%

发文量

809

审稿时长

63 days

期刊介绍： NeuroImage, a Journal of Brain Function provides a vehicle for communicating important advances in acquiring, analyzing, and modelling neuroimaging data and in applying these techniques to the study of structure-function and brain-behavior relationships. Though the emphasis is on the macroscopic level of human brain organization, meso-and microscopic neuroimaging across all species will be considered if informative for understanding the aforementioned relationships.