Yuan Pubing, Huang Yonghua, Dai Minghui, Jin Xin, Zheng Dingxin, Xiao Die, Deng Lihua, Ou Peiling, Shi Linfeng, Chen Yifan, Wang Jian, Chen Wei, Zhang Yuanchao, Liu Chen
The Clinical Hospital of Chengdu Brain Science Institute, MOE Key Lab for Neuroinformation, University of Electronic Science and Technology of China, Chengdu, People's Republic of China.
School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, 610054, People's Republic of China.
Orphanet J Rare Dis. 2025 Jun 4;20(1):275. doi: 10.1186/s13023-025-03803-3.
Spinocerebellar ataxia type 3 (SCA3) is a progressive neurodegenerative disease characterized by heterogeneous motor and nonmotor manifestations. The progressive pattern of subcortical shape abnormalities and their associations with the clinical phenotypes in SCA3 remain unknown.
Tract-based spatial statistics (TBSS) and FSL-FIRST were used to characterize the progressive patterns of the abnormalities in white matter microstructure and subcortical shape in four subgroups of SCA3 patients stratified based on disease duration (n = 56). These were compared to matched healthy control groups (n = 59).
TBSS analyses revealed a clear progressive pattern of white matter microstructural abnormalities throughout the course of SCA3, as indicated by an expanding topographic distribution of fractional anisotropy (FA) reductions that originated from the cerebellar peduncle. Vertex-based shape analyses uncovered an increasing number of affected subcortical structures in symptomatic patients as the disease progressed with concurrent inward atrophy and outward inflation in subcortical structures including the bilateral thalamus, caudate, putamen, pallidum, hippocampus and brainstem. Moreover, the localized shape changes of subcortical structures correlated bidirectionally with clinical measurements including the length of CAG repeats within the ATXN3 gene, the scores on the scale of the assessment, the rating of ataxia, the instrumental activities of daily living scale, and the mini-mental state examination.
We demonstrated progressive, localized, and bidirectional changes in the shape of subcortical structures that related to diverse clinical manifestations in SCA3, highlighting the pivotal role of localized shape abnormalities in contributing to the clinical heterogeneity of this disorder.
Imaging genetics study the relationship between MJD1 gene and cognitive impairment with Spinocerebellar Ataxia type 3, ChiCTR1800019901. Registered 8 December 2018 and ChiCTR2000039434. Registered 28 October 2020, http://chictr.org.cn .
3型脊髓小脑共济失调（SCA3）是一种进行性神经退行性疾病，具有异质性的运动和非运动表现。SCA3患者皮质下形状异常的进展模式及其与临床表型的关联尚不清楚。
基于体素的空间统计学（TBSS）和FSL-FIRST被用于描述根据病程分层的四组SCA3患者（n = 56）白质微观结构和皮质下形状异常的进展模式。将这些结果与匹配的健康对照组（n = 59）进行比较。
TBSS分析显示，在整个SCA3病程中，白质微观结构异常呈现出明显的进展模式，表现为各向异性分数（FA）降低的地形分布不断扩大，起源于小脑脚。基于顶点的形状分析发现，随着疾病进展，有症状患者中受影响的皮质下结构数量增加，同时包括双侧丘脑、尾状核、壳核、苍白球、海马体和脑干在内的皮质下结构出现向内萎缩和向外膨胀。此外，皮质下结构的局部形状变化与临床测量指标呈双向相关，这些指标包括ATXN3基因内CAG重复序列的长度、评估量表评分、共济失调评分、日常生活活动能力量表评分和简易精神状态检查评分。
我们证明了SCA3患者皮质下结构形状的进行性、局部性和双向性变化与多种临床表现相关，突出了局部形状异常在导致该疾病临床异质性方面的关键作用。
成像遗传学研究MJD1基因与3型脊髓小脑共济失调认知障碍的关系，ChiCTR1800019901。于2018年12月8日注册，ChiCTR2000039434。于2020年10月28日注册，http://chictr.org.cn 。
