The Natural History of Spinocerebellar Ataxia Type 3 in Mainland China: A 2-Year Cohort Study

• Authors: Yun Peng, Central South University; Linliu Peng, Central South University; Zhao Chen, Central South University; Huirong Peng, Central South University; Puzhi Wang, Central South University; Youming Zhang, Central South University; Yangping Li, Emory University; Chunrong Wang, Central South University; Yuting Shi, Central South University; Xuan Hou, Central South University; Zhe Long, Central South University; Hongyu Yuan, Central South University; Na Wan, Central South University; Linlin Wan, Central South University; Keqin Xu, Central South University; Lijing Lei, Central South University; Shang Wang, Central South University; Lang He, Central South University; Yue Xie, Central South University; Yiqing Gong, Central South University; Qi Deng, Central South University; Guangdong Zou, Central South University; Zhichao Tang, Central South University; Lu Shen, Central South University; Kun Xia, Central South University; Rong Qiu, Central South University; Thomas Klockgether, University of Bonn; Beisha Tang, Central South University; Hong Jiang, Central South University
• Journal Title: FRONTIERS IN AGING NEUROSCIENCE
• Volume: Volume 14
• Publisher: FRONTIERS MEDIA SA | 2022-07-05, Pages 917126-917126
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.3389/fnagi.2022.917126
• Subjects: Health Sciences, Radiology; Health Sciences, Pathology
• Keywords: Science & Technology; Life Sciences & Biomedicine; Geriatrics & Gerontology; Neurosciences; Neurosciences & Neurology; spinocerebellar ataxia type 3; ATXN3; natural history; disease progression; Machado-Joseph disease (MJD); DISEASE PROGRESSION

Abstract

Objective: The natural history of spinocerebellar ataxia type 3 (SCA3) has been reported in several populations and shows heterogeneity in progression rate and affecting factors. However, it remains unexplored in the population of Mainland China. This study aimed to identify the disease progression rate and its potential affecting factors in patients with SCA3 in Mainland China. Participants and Methods: We enrolled patients with genetically confirmed SCA3 in Mainland China. Patients were seen at three visits, i.e., baseline, 1 year, and 2 years. The primary outcome was the Scale for the Assessment and Rating of Ataxia (SARA), and the secondary outcomes were the Inventory of Non-Ataxia Signs (INAS) as well as the SCA Functional Index (SCAFI). Results: Between 1 October 2015, and 30 September 2016, we enrolled 263 patients with SCA3. We analyzed 247 patients with at least one follow-up visit. The annual progression rate of SARA was 1.49 points per year (SE 0.08, 95% confidence interval [CI] 1.33–1.65, p < 0.0001). The annual progression rates of INAS and SCAFI were 0.56 points per year (SE 0.05, 95% CI 0.47–0.66, p < 0.001) and −0.30 points per year (SE 0.01, 95% CI −0.33∼-0.28, p < 0.001), respectively. Faster progression in SARA was associated with longer length of the expanded allele of ATXN3 (p < 0.0001); faster progression in INAS was associated with lower INAS at baseline (p < 0.0001); faster decline in SCAFI was associated with shorter length of the normal allele of ATXN3 (p = 0.036) and higher SCAFI at baseline (p < 0.0001). Conclusion: Our results provide quantitative data on the disease progression of patients with SCA3 in Mainland China and its corresponding affecting factors, which could facilitate the sample size calculation and patient stratification in future clinical trials. Trial Registration: This study was registered with Chictr.org on 15 September 2015, number ChiCTR-OOC-15007124.