AUTHOR=Peng Yun , Peng Linliu , Chen Zhao , Peng Huirong , Wang Puzhi , Zhang Youming , Li Yangping , Wang Chunrong , Shi Yuting , Hou Xuan , Long Zhe , Yuan Hongyu , Wan Na , Wan Linlin , Xu Keqin , Lei Lijing , Wang Shang , He Lang , Xie Yue , Gong Yiqing , Deng Qi , Zou Guangdong , Tang Zhichao , Shen Lu , Xia Kun , Qiu Rong , Klockgether Thomas , Tang Beisha , Jiang Hong 

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

JOURNAL=Frontiers in Aging Neuroscience

VOLUME=14

YEAR=2022

URL=https://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2022.917126

DOI=10.3389/fnagi.2022.917126

ISSN=1663-4365

ABSTRACT=<sec><title>Objective</title><p>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.</p></sec><sec><title>Participants and Methods</title><p>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).</p></sec><sec><title>Results</title><p>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, <italic>p</italic> &lt; 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, <italic>p</italic> &lt; 0.001) and −0.30 points per year (SE 0.01, 95% CI −0.33∼-0.28, <italic>p</italic> &lt; 0.001), respectively. Faster progression in SARA was associated with longer length of the expanded allele of <italic>ATXN3</italic> (<italic>p</italic> &lt; 0.0001); faster progression in INAS was associated with lower INAS at baseline (<italic>p</italic> &lt; 0.0001); faster decline in SCAFI was associated with shorter length of the normal allele of <italic>ATXN3</italic> (<italic>p</italic> = 0.036) and higher SCAFI at baseline (<italic>p</italic> &lt; 0.0001).</p></sec><sec><title>Conclusion</title><p>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.</p></sec><sec><title>Trial Registration</title><p>This study was registered with <ext-link ext-link-type="uri" xlink:href="http://Chictr.org" xmlns:xlink="http://www.w3.org/1999/xlink">Chictr.org</ext-link> on 15 September 2015, number ChiCTR-OOC-15007124.</p></sec>