Progressive subcortical involvement as spinocerebellar ataxia type 3 advances
Abstract Background and objectives 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...
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BMC
2025-06-01
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| Series: | Orphanet Journal of Rare Diseases |
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| Online Access: | https://doi.org/10.1186/s13023-025-03803-3 |
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| author | Pubing Yuan Yonghua Huang Minghui Dai Xin Jin Dingxin Zheng Die Xiao Lihua Deng Peiling Ou Linfeng Shi Yifan Chen Jian Wang Wei Chen Yuanchao Zhang Chen Liu |
| author_facet | Pubing Yuan Yonghua Huang Minghui Dai Xin Jin Dingxin Zheng Die Xiao Lihua Deng Peiling Ou Linfeng Shi Yifan Chen Jian Wang Wei Chen Yuanchao Zhang Chen Liu |
| author_sort | Pubing Yuan |
| collection | DOAJ |
| description | Abstract Background and objectives 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. Methods 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). Results 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. Conclusion 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. Trial registration 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 . |
| format | Article |
| id | doaj-art-7bd4e614793a4922b8ae552f13eab56e |
| institution | DOAJ |
| issn | 1750-1172 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Orphanet Journal of Rare Diseases |
| spelling | doaj-art-7bd4e614793a4922b8ae552f13eab56e2025-08-20T03:10:38ZengBMCOrphanet Journal of Rare Diseases1750-11722025-06-0120111010.1186/s13023-025-03803-3Progressive subcortical involvement as spinocerebellar ataxia type 3 advancesPubing Yuan0Yonghua Huang1Minghui Dai2Xin Jin3Dingxin Zheng4Die Xiao5Lihua Deng6Peiling Ou7Linfeng Shi8Yifan Chen9Jian Wang10Wei Chen11Yuanchao Zhang12Chen Liu13The Clinical Hospital of Chengdu Brain Science Institute, MOE Key Lab for Neuroinformation, University of Electronic Science and Technology of China7T Magnetic Resonance Imaging Translational Medical Center, Southwest Hospital, Army Medical University (Third Military Medical University)The Clinical Hospital of Chengdu Brain Science Institute, MOE Key Lab for Neuroinformation, University of Electronic Science and Technology of ChinaThe Clinical Hospital of Chengdu Brain Science Institute, MOE Key Lab for Neuroinformation, University of Electronic Science and Technology of ChinaThe Clinical Hospital of Chengdu Brain Science Institute, MOE Key Lab for Neuroinformation, University of Electronic Science and Technology of ChinaThe Clinical Hospital of Chengdu Brain Science Institute, MOE Key Lab for Neuroinformation, University of Electronic Science and Technology of China7T Magnetic Resonance Imaging Translational Medical Center, Southwest Hospital, Army Medical University (Third Military Medical University)7T Magnetic Resonance Imaging Translational Medical Center, Southwest Hospital, Army Medical University (Third Military Medical University)7T Magnetic Resonance Imaging Translational Medical Center, Southwest Hospital, Army Medical University (Third Military Medical University)The Clinical Hospital of Chengdu Brain Science Institute, MOE Key Lab for Neuroinformation, University of Electronic Science and Technology of China7T Magnetic Resonance Imaging Translational Medical Center, Southwest Hospital, Army Medical University (Third Military Medical University)MR Research Collaboration Team, Siemens Healthineers Ltd.The Clinical Hospital of Chengdu Brain Science Institute, MOE Key Lab for Neuroinformation, University of Electronic Science and Technology of China7T Magnetic Resonance Imaging Translational Medical Center, Southwest Hospital, Army Medical University (Third Military Medical University)Abstract Background and objectives 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. Methods 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). Results 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. Conclusion 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. Trial registration 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 .https://doi.org/10.1186/s13023-025-03803-3FSL-FIRSTATXN3Spinocerebellar ataxia type 3 (SCA3)Tract-based spatial statistics (TBSS) |
| spellingShingle | Pubing Yuan Yonghua Huang Minghui Dai Xin Jin Dingxin Zheng Die Xiao Lihua Deng Peiling Ou Linfeng Shi Yifan Chen Jian Wang Wei Chen Yuanchao Zhang Chen Liu Progressive subcortical involvement as spinocerebellar ataxia type 3 advances Orphanet Journal of Rare Diseases FSL-FIRST ATXN3 Spinocerebellar ataxia type 3 (SCA3) Tract-based spatial statistics (TBSS) |
| title | Progressive subcortical involvement as spinocerebellar ataxia type 3 advances |
| title_full | Progressive subcortical involvement as spinocerebellar ataxia type 3 advances |
| title_fullStr | Progressive subcortical involvement as spinocerebellar ataxia type 3 advances |
| title_full_unstemmed | Progressive subcortical involvement as spinocerebellar ataxia type 3 advances |
| title_short | Progressive subcortical involvement as spinocerebellar ataxia type 3 advances |
| title_sort | progressive subcortical involvement as spinocerebellar ataxia type 3 advances |
| topic | FSL-FIRST ATXN3 Spinocerebellar ataxia type 3 (SCA3) Tract-based spatial statistics (TBSS) |
| url | https://doi.org/10.1186/s13023-025-03803-3 |
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