Natural History of Spinocerebellar Ataxia Type 31: a 4-Year Prospective Study

Abstract

Spinocerebellar ataxia type 31 (SCA31) is known as a late-onset, relatively pure cerebellar form of ataxia, but a longitudinal prospective study on the natural history of SCA31 has not been done yet. In this prospective cohort study, we enrolled 44 patients (mean ± standard deviation 73.6 ± 8.5 years) with genetically confirmed SCA31 from 10 ataxia referral centers in the Nagano area, Japan. Patients were evaluated every year for 4 years using the Scale for the Assessment and Rating of Ataxia (SARA) and the Barthel Index (BI). Of the 176 follow-up visits (91.5%), 161 were completed in this study. Five patients (11.4%) died during the follow-up period, and two patients (4.5%) were lost to follow-up. The annual progression of the SARA score was 0.8 ± 0.1 points/year and that of the BI was -2.3 ± 0.4 points/year (mean ± standard error). Shorter disease duration at baseline was associated with faster progression of the SARA score. Our study indicated the averaged clinical course of SCA31 as follows: the patients develop ataxic symptoms at 58.5 ± 10.3 years, become wheelchair bound at 79.4 ± 1.7 years, and died at 88.5 ± 0.7 years. Our prospective dataset provides important information for clinical trials of forthcoming disease-modifying therapies for cerebellar ataxia. It also represents a useful resource for SCA31 patients and their family members in genetic counseling sessions.

Molecular Mechanisms and Future Therapeutics for Spinocerebellar Ataxia Type 31 (SCA31)

“…Identification of SCA31 repeat clarified clinical picture of SCA31. Typical clinical features can be found in some case reports and cohort studies [10][11][12]. Sakakibara and her colleagues [10] studied 6 SCA31 patients.…”

“…Magnetic resonance imaging of his brain revealed cerebellar atrophy most pronounced in the upper vermis, which is typical for SCA31. Nakamura and his colleagues collected 44 patients with SCA31 and underwent a 4-year prospective study [12]. They evaluated patients yearly using the Scale for the Assessment and Rating of Ataxia (SARA) and the Barthel Index (BI).…”

Repeat expansion diseases

“…SCA 31 is a relatively pure cerebellar ataxia with a mean onset at approximately 60 years of age and compatible with a normal life span (100). Originally described in Japan, where it is the third most common form of SCA, SCA31 has since been discovered in other ethnic populations (64,119).…”

Effect of rovatirelin in patients with cerebellar ataxia: two randomised double-blind placebo-controlled phase 3 trials

“…However, progression of SCD is generally slow. It has been reported that the annual changes in SARA total score are 0.80–1.33 for SCA6 and 0.8 for SCA31 2 22 23. Considering the sensitivity of SARA and slow progression, limited change in SARA total score was expected during the observation period selected for our study.…”

“…Although the number of repeats can influence the clinical severity of SCA6 and SCA31, data on the number of repeats were not obtained. However, as the effect of the number of repeats on the pathological condition is often subtle in these diseases, this lack of data was considered to be inconsequential 2 23 28. As genetic analyses were not essentially required for CCA diagnosis, it is possible that patients with SCA6, SCA31 or other genetic disorders were included in these studies.…”