Rahimi Parya, Mareček Stanislav, Brůha Radan, Dezortová Monika, Sojka Petr, Hájek Milan, Skowrońska Marta, Smoliński Łukasz, Urbánek Petr, Litwin Tomasz, Dušek Petr
Department of Neurology and Center of Clinical Neuroscience, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czechia.
Fourth Department of Internal Medicine, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czechia.
J Inherit Metab Dis. 2025 Jan;48(1):e12814. doi: 10.1002/jimd.12814. Epub 2024 Nov 19.
Wilson disease (WD) primarily presents with hepatic and neurological symptoms. While hepatic symptoms typically precede the neurological manifestations, copper accumulates in the brain already in this patient group and leads to subclinical brain MRI abnormalities including T2 hyperintensities and atrophy. This study aimed to assess brain morphological changes in mild hepatic WD. WD patients without a history of neurologic symptoms and decompensated cirrhosis and control participants underwent brain MRI at 3T scanner including high-resolution T1-weighted images. A volumetric evaluation was conducted on the following brain regions: nucleus accumbens, caudate, pallidum, putamen, thalamus, amygdala, hippocampus, midbrain, pons, cerebellar gray matter, white matter (WM), and superior peduncle, using Freesurfer v7 software. Whole-brain analyses using voxel- and surface-based morphometry were performed using SPM12. Statistical comparisons utilized a general linear model adjusted for total intracranial volume, age, and sex. Twenty-six WD patients with mild hepatic form (30 ± 9 years [mean age ± SD]); 11 women; mean treatment duration 13 ± 12 (range 0-42) years and 28 healthy controls (33 ± 9 years; 15 women) were evaluated. Volumetric analysis revealed a significantly smaller pons volume and a trend for smaller midbrain and cerebellar WM in WD patients compared to controls. Whole-brain analysis revealed regions of reduced volume in the pons, cerebellar, and lobar WM in the WD group. No significant differences in gray matter density or cortical thickness were found. Myelin or WM in general seems vulnerable to low-level copper toxicity, with WM volume loss showing promise as a marker for assessing brain involvement in early WD stages.
威尔逊病（WD）主要表现为肝脏和神经症状。虽然肝脏症状通常先于神经表现出现，但在这组患者中，铜已在大脑中蓄积，并导致亚临床脑磁共振成像（MRI）异常，包括T2高信号和萎缩。本研究旨在评估轻度肝脏型WD患者的脑形态学变化。无神经症状和失代偿性肝硬化病史的WD患者以及对照参与者在3T扫描仪上进行脑MRI检查，包括高分辨率T1加权图像。使用Freesurfer v7软件对以下脑区进行体积评估：伏隔核、尾状核、苍白球、壳核、丘脑、杏仁核、海马体、中脑、脑桥、小脑灰质、白质（WM）和上脚。使用SPM12进行基于体素和表面形态学的全脑分析。统计比较采用针对总颅内体积、年龄和性别进行调整的一般线性模型。对26例轻度肝脏型WD患者（年龄30±9岁[平均年龄±标准差]；11名女性；平均治疗时间13±12（范围0 - 42）年）和28名健康对照者（年龄33±9岁；15名女性）进行了评估。体积分析显示，与对照组相比，WD患者的脑桥体积明显较小，中脑和小脑白质体积有减小趋势。全脑分析显示WD组脑桥、小脑和脑叶白质体积减小区域。未发现灰质密度或皮质厚度有显著差异。一般来说，髓鞘或白质似乎易受低水平铜毒性影响，白质体积减少有望作为评估WD早期脑受累情况的标志物。
