Ding Yufeng, Cao Kegang, Yang Wenming, Hu Sheng, Zhang Jing, Yang Yulong, Zhang Xuran
Department of Neurology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China.
Department of Neurology, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, Anhui, China.
Front Neurol. 2025 Jun 5;16:1560848. doi: 10.3389/fneur.2025.1560848. eCollection 2025.
Neurodegenerative changes are key manifestations of Wilson disease (WD), causing neurological symptoms including parkinsonism, tremors, and dystonia. However, the neuroimaging correlates of specific neurological manifestations (especially dystonia) in WD remain poorly characterized.
37 WD patients and 37 healthy controls (HC) were recruited. All subjects underwent structural magnetic resonance scanning, muscle biomechanical measurements, and the Unified Wilson Disease Rating Scale for Neurology (UWDRS-N) assessment. Neurodegenerative changes, identified as gray matter volume (GV) changes, were analyzed via voxel-based morphometry (VBM) in WD compared to HC. Clinical symptoms were linked to GV changes in WD patients' brains.
Compared with HC, WD patients had GV loss in the bilateral caudate nucleus, putamen, cerebellum (Crus1), left amygdala, right posterior insular lobe, and right parahippocampal gyrus and increased GV in the bilateral anterior insular lobes. In cortical areas, UWDRS-N significantly negatively correlated with GV in the bilateral posterior insula lobes, part of temporal lobe, optic cortex, frontal lobe, and cingulate cortex, while positively correlated with that in bilateral anterior insular lobes and putamen. Moreover, the GV from the left parahippocampal gyrus, bilateral hippocampus, and bilateral caudate nucleus showed a strong positive correlation with the value of the right gastrocnemius medial head.
In WD patients with neurological symptoms, obvious abnormal GV values in the cortico-striatal-thalamo-cortical (CSTC) circuit were noted. These GV changes were linked to UWDRS-N and correlated with muscle tension. The study mapped UWDRS-N and muscle biomechanics in GV-impaired areas, suggesting altered GV (especially in basal ganglia) as a key imaging sign of WD severity. This indicates that the CSTC circuit could act as a biomarker for WD neurological symptoms and affect WD dystonia mechanisms. Additionally, it shows that muscle-related biological parameters can assess WD dystonia severity and neurological damage.
clinicaltrials.gov, identifier NCT05305872.
神经退行性变是威尔逊病（WD）的关键表现，可导致包括帕金森综合征、震颤和肌张力障碍在内的神经症状。然而，WD中特定神经表现（尤其是肌张力障碍）的神经影像学相关性仍未得到充分描述。
招募了37例WD患者和37名健康对照者（HC）。所有受试者均接受了结构磁共振扫描、肌肉生物力学测量以及统一威尔逊病神经评分量表（UWDRS-N）评估。与HC相比，通过基于体素的形态计量学（VBM）分析WD中被确定为灰质体积（GV）变化的神经退行性变。将临床症状与WD患者大脑中的GV变化相关联。
与HC相比，WD患者双侧尾状核、壳核、小脑（脚1）、左侧杏仁核、右侧岛叶后叶和右侧海马旁回的GV减少，双侧岛叶前叶的GV增加。在皮质区域，UWDRS-N与双侧岛叶后叶、部分颞叶、视皮质、额叶和扣带回皮质的GV呈显著负相关，而与双侧岛叶前叶和壳核的GV呈正相关。此外，左侧海马旁回、双侧海马和双侧尾状核的GV与右侧腓肠肌内侧头肌值呈强正相关。
在有神经症状的WD患者中，注意到皮质-纹状体-丘脑-皮质（CSTC）回路中明显的异常GV值。这些GV变化与UWDRS-N相关，并与肌肉张力相关。该研究描绘了GV受损区域的UWDRS-N和肌肉生物力学，表明GV改变（尤其是在基底神经节）是WD严重程度的关键影像学标志。这表明CSTC回路可作为WD神经症状的生物标志物，并影响WD肌张力障碍机制。此外，研究表明与肌肉相关的生物学参数可评估WD肌张力障碍的严重程度和神经损伤。
clinicaltrials.gov，标识符NCT05305872。
