YNIMG Journal 2026 Journal Article
Glymphatic system impairment in Wilson’s disease: An overlooked mechanism for neurological dysfunction?
- Gaiying Li
- Siyuan Fang
- Yupeng Wu
- Xiangzhen Yuan
- Ying Tang
- Xiaozhong Jing
- Luguang Chen
- Xiaoping Wang
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: ) 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: 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.