TY - JOUR
T1 - The S-Factor, a New Measure of Disease Severity in Spinocerebellar Ataxia
T2 - Findings and Implications
AU - Selvadurai, Louisa P.
AU - Perlman, Susan L.
AU - Wilmot, George R.
AU - Subramony, Sub H.
AU - Gomez, Christopher M.
AU - Ashizawa, Tetsuo
AU - Paulson, Henry L.
AU - Onyike, Chiadi U.
AU - Rosenthal, Liana S.
AU - Sair, Haris I.
AU - Kuo, Sheng Han
AU - Ratai, Eva Maria
AU - Zesiewicz, Theresa A.
AU - Bushara, Khalaf O.
AU - Öz, Gülin
AU - Dietiker, Cameron
AU - Geschwind, Michael D.
AU - Nelson, Alexandra B.
AU - Opal, Puneet
AU - Yacoubian, Talene A.
AU - Nopoulos, Peggy C.
AU - Shakkottai, Vikram G.
AU - Figueroa, Karla P.
AU - Pulst, Stefan M.
AU - Morrison, Peter E.
AU - Schmahmann, Jeremy D.
N1 - Publisher Copyright:
© 2022, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
PY - 2023/10
Y1 - 2023/10
N2 - Spinocerebellar ataxias (SCAs) are progressive neurodegenerative disorders, but there is no metric that predicts disease severity over time. We hypothesized that by developing a new metric, the Severity Factor (S-Factor) using immutable disease parameters, it would be possible to capture disease severity independent of clinical rating scales. Extracting data from the CRC-SCA and READISCA natural history studies, we calculated the S-Factor for 438 participants with symptomatic SCA1, SCA2, SCA3, or SCA6, as follows: ((length of CAG repeat expansion – maximum normal repeat length) /maximum normal repeat length) × (current age – age at disease onset) × 10). Within each SCA type, the S-Factor at the first Scale for the Assessment and Rating of Ataxia (SARA) visit (baseline) was correlated against scores on SARA and other motor and cognitive assessments. In 281 participants with longitudinal data, the slope of the S-Factor over time was correlated against slopes of scores on SARA and other motor rating scales. At baseline, the S-Factor showed moderate-to-strong correlations with SARA and other motor rating scales at the group level, but not with cognitive performance. Longitudinally the S-Factor slope showed no consistent association with the slope of performance on motor scales. Approximately 30% of SARA slopes reflected a trend of non-progression in motor symptoms. The S-Factor is an observer-independent metric of disease burden in SCAs. It may be useful at the group level to compare cohorts at baseline in clinical studies. Derivation and examination of the S-factor highlighted challenges in the use of clinical rating scales in this population.
AB - Spinocerebellar ataxias (SCAs) are progressive neurodegenerative disorders, but there is no metric that predicts disease severity over time. We hypothesized that by developing a new metric, the Severity Factor (S-Factor) using immutable disease parameters, it would be possible to capture disease severity independent of clinical rating scales. Extracting data from the CRC-SCA and READISCA natural history studies, we calculated the S-Factor for 438 participants with symptomatic SCA1, SCA2, SCA3, or SCA6, as follows: ((length of CAG repeat expansion – maximum normal repeat length) /maximum normal repeat length) × (current age – age at disease onset) × 10). Within each SCA type, the S-Factor at the first Scale for the Assessment and Rating of Ataxia (SARA) visit (baseline) was correlated against scores on SARA and other motor and cognitive assessments. In 281 participants with longitudinal data, the slope of the S-Factor over time was correlated against slopes of scores on SARA and other motor rating scales. At baseline, the S-Factor showed moderate-to-strong correlations with SARA and other motor rating scales at the group level, but not with cognitive performance. Longitudinally the S-Factor slope showed no consistent association with the slope of performance on motor scales. Approximately 30% of SARA slopes reflected a trend of non-progression in motor symptoms. The S-Factor is an observer-independent metric of disease burden in SCAs. It may be useful at the group level to compare cohorts at baseline in clinical studies. Derivation and examination of the S-factor highlighted challenges in the use of clinical rating scales in this population.
KW - Disease progression
KW - Natural history
KW - Scale for the Assessment and Rating of Ataxia
KW - Spinocerebellar ataxia
KW - Patient Acuity
KW - Humans
KW - Spinocerebellar Ataxias/diagnosis
KW - Disease Progression
UR - http://www.scopus.com/inward/record.url?scp=85135834830&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85135834830&partnerID=8YFLogxK
U2 - 10.1007/s12311-022-01424-1
DO - 10.1007/s12311-022-01424-1
M3 - Article
C2 - 35962273
AN - SCOPUS:85135834830
SN - 1473-4222
VL - 22
SP - 790
EP - 809
JO - Cerebellum
JF - Cerebellum
IS - 5
ER -