Microstructural Alterations in Asymptomatic and Symptomatic Patients with Spinocerebellar Ataxia Type 3: A Tract-Based Spatial Statistics Study

Xinwei Wu; Xinxin Liao; Yafeng Zhan; Cheng Cheng; Wei Shen; Mufang Huang; Zhifan Zhou; Zheng Wang; Zilong Qiu; Wu Xing; Weihua Liao; Beisha Tang; Lu Shen

doi:10.3389/fneur.2017.00714

Microstructural Alterations in Asymptomatic and Symptomatic Patients with Spinocerebellar Ataxia Type 3: A Tract-Based Spatial Statistics Study

Front Neurol. 2017 Dec 22:8:714. doi: 10.3389/fneur.2017.00714. eCollection 2017.

Authors

Xinwei Wu¹, Xinxin Liao¹, Yafeng Zhan², Cheng Cheng², Wei Shen¹, Mufang Huang¹, Zhifan Zhou¹, Zheng Wang², Zilong Qiu², Wu Xing³, Weihua Liao³, Beisha Tang^{1

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5

6

7

8

9}, Lu Shen^{1

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Affiliations

¹ Department of Neurology, Xiangya Hospital, Central South University, Changsha, China.
² Institute of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, China.
³ Department of Radiology, Xiangya Hospital, Central South University, Changsha, China.
⁴ Key Laboratory of Hunan Province in Neurodegenerative Disorders, Central South University, Changsha, China.
⁵ State Key Laboratory of Medical Genetics, Changsha, China.
⁶ National Clinical Research Center for Geriatric Disease, Changsha, China.
⁷ Parkinson's Disease Center of Beijing Institute for Brain Disorders, Beijing, China.
⁸ Collaboration Innovation Center for Brain Science, Shanghai, China.
⁹ Collaboration Innovation Center for Genetics and Development, Changsha, China.

Abstract

Objective: Spinocerebellar ataxia type 3 (SCA3) is the most commonly occurring type of autosomal dominant spinocerebellar ataxia. The present study aims to investigate progressive changes in white matter (WM) fiber in asymptomatic and symptomatic patients with SCA3.

Methods: A total of 62 participants were included in this study. Among them, 16 were asymptomatic mutation carriers (pre-SCA3), 22 were SCA3 patients with clinical symptoms, and 24 were normal controls (NC). Group comparison of tract-based spatial statistics was performed to identify microstructural abnormalities at different SCA3 disease stages.

Results: Decreased fractional anisotropy (FA) and increased mean diffusivity (MD) were found in the left inferior cerebellar peduncle and superior cerebellar peduncle (SCP) in the pre-SCA3 group compared with NC. The symptomatic SCA3 group showed brain-wide WM tracts impairment in both supratentorial and infratentorial networks, and the mean FA value of the WM skeleton showed a significantly negative correlation with the International Cooperative Ataxia Rating Scale (ICARS) scores. Specifically, FA of the bilateral posterior limb of the internal capsule negatively correlated with SCA3 disease duration. We also found that FA values in the right medial lemniscus and SCP negatively correlated with ICARS scores, whereas FA in the right posterior thalamic radiation positively correlated with Montreal Cognitive Assessment scores. In addition, MD in the middle cerebellar peduncle, left anterior limb of internal capsule, external capsule, and superior corona radiate positively correlated with ICARS scores in SCA3 patients.

Conclusion: WM microstructural changes are present even in the asymptomatic stages of SCA3. In individuals in which the disease has progressed to the symptomatic stage, the integrity of WM fibers across the whole brain is affected. Furthermore, abnormalities in WM tracts are closely related to SCA3 disease severity, including movement disorder and cognitive dysfunction. These findings can deepen our understanding of the neural basis of SCA3 dysfunction.

Keywords: asymptomatic; ataxia; spinocerebellar ataxia type 3; tract-based spatial statistics; white matter tracts.