TY - JOUR
T1 - Differential Temporal Dynamics of Axial and Appendicular Ataxia in SCA3
AU - Maas, Roderick P.P.W.M.
AU - Teerenstra, Steven
AU - Lima, Manuela
AU - Pires, Paula
AU - Pereira de Almeida, Luís
AU - van Gaalen, Judith
AU - Timmann, Dagmar
AU - Infante, Jon
AU - Onyike, Chiadi
AU - Bushara, Khalaf
AU - Jacobi, Heike
AU - Reetz, Kathrin
AU - Santana, Magda M.
AU - Afonso Ribeiro, Joana
AU - Hübener-Schmid, Jeannette
AU - de Vries, Jeroen J.
AU - Synofzik, Matthis
AU - Schöls, Ludger
AU - Garcia-Moreno, Hector
AU - Giunti, Paola
AU - Faber, Jennifer
AU - Klockgether, Thomas
AU - van de Warrenburg, Bart P.C.
N1 - Publisher Copyright:
© 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
PY - 2022/9
Y1 - 2022/9
N2 - Background: Disease severity in spinocerebellar ataxia type 3 (SCA3) is commonly defined by the Scale for the Assessment and Rating of Ataxia (SARA) sum score, but little is known about the contributions and progression patterns of individual items. Objectives: To investigate the temporal dynamics of SARA item scores in SCA3 patients and evaluate if clinical and demographic factors are differentially associated with evolution of axial and appendicular ataxia. Methods: In a prospective, multinational cohort study involving 11 European and 2 US sites, SARA scores were determined longitudinally in 223 SCA3 patients with a follow-up assessment after 1 year. Results: An increase in SARA score from 10 to 20 points was mainly driven by axial and speech items, with a markedly smaller contribution of appendicular items. Finger chase and nose-finger test scores not only showed the lowest variability at baseline, but also the least deterioration at follow-up. Compared with the full set of SARA items, omission of both tests would result in lower sample size requirements for therapeutic trials. Sex was associated with change in SARA sum score and appendicular, but not axial, subscore, with a significantly faster progression in men. Despite considerable interindividual variability, the average annual progression rate of SARA score was approximately three times higher in subjects with a disease duration over 10 years than in those within 10 years from onset. Conclusion: Our findings provide evidence for a difference in temporal dynamics between axial and appendicular ataxia in SCA3 patients, which will help inform the design of clinical trials and development of new (etiology-specific) outcome measures.
AB - Background: Disease severity in spinocerebellar ataxia type 3 (SCA3) is commonly defined by the Scale for the Assessment and Rating of Ataxia (SARA) sum score, but little is known about the contributions and progression patterns of individual items. Objectives: To investigate the temporal dynamics of SARA item scores in SCA3 patients and evaluate if clinical and demographic factors are differentially associated with evolution of axial and appendicular ataxia. Methods: In a prospective, multinational cohort study involving 11 European and 2 US sites, SARA scores were determined longitudinally in 223 SCA3 patients with a follow-up assessment after 1 year. Results: An increase in SARA score from 10 to 20 points was mainly driven by axial and speech items, with a markedly smaller contribution of appendicular items. Finger chase and nose-finger test scores not only showed the lowest variability at baseline, but also the least deterioration at follow-up. Compared with the full set of SARA items, omission of both tests would result in lower sample size requirements for therapeutic trials. Sex was associated with change in SARA sum score and appendicular, but not axial, subscore, with a significantly faster progression in men. Despite considerable interindividual variability, the average annual progression rate of SARA score was approximately three times higher in subjects with a disease duration over 10 years than in those within 10 years from onset. Conclusion: Our findings provide evidence for a difference in temporal dynamics between axial and appendicular ataxia in SCA3 patients, which will help inform the design of clinical trials and development of new (etiology-specific) outcome measures.
KW - Scale for the Assessment and Rating of Ataxia
KW - disease progression
KW - natural history
KW - spinocerebellar ataxia type 3
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U2 - 10.1002/mds.29135
DO - 10.1002/mds.29135
M3 - Article
C2 - 35808813
AN - SCOPUS:85133581544
SN - 0885-3185
VL - 37
SP - 1850
EP - 1860
JO - Movement Disorders
JF - Movement Disorders
IS - 9
ER -