Axial Function Reflects Global Severity in Inherited Ataxias: The Upright Stability Score in Ambulatory Friedreich vs. Spinocerebellar Ataxia

@article{rummey2026axial,
  title = {{Axial Function Reflects Global Severity in Inherited Ataxias: The Upright Stability Score in Ambulatory Friedreich vs. Spinocerebellar Ataxia}},
  author = {Christian Rummey and S. H. Subramony and David R. Lynch and Louise A. Corben and Martin B. Delatycki and Jörg B. Schulz and Kathrin Reetz and Massimo Pandolfo and Matthis Synofzik and Theresa Zesiewicz and Antoine Duquette and Matthew Burns and Martin Vyhnálek and Lucie Stovickova and Sinead M. Murphy and Petya Bogdanova‐Mihaylova and Mary Kearney and Richard Walsh and Richard H. Roxburgh and Khalaf Bushara and Marie Y. Davis and Enrico S. Bertini and Gessica Vasco and Shweta Sahni and Mohammed Faruq and Achal K. Srivastava and Bart van de Warrenburg and Elisabetta Indelicato and Sylvia Boesch and Andrew Billnitzer and Tetsuo Ashizawa and Anoopum S. Gupta and Grace Yoon and Georgios Koutsis and Chrysoula Koniari and Zofia Fleszar and Christopher M. Gomez and Andrea Martinuzzi and Gabriella Paparella and Ali G. Hamedani and Puneet Opal and Rizwan S. Akhtar and Caterina Mariotti and Henry Paulson and Peter Todd and Sharan R. Srinivasan and George Wilmot and Ludger Schöls and Susan Perlman and Jeremy D. Schmahmann and Sheng‐Han Kuo and Liana S. Rosenthal and Vikram G. Shakkottai},
  journal = {Annals of Clinical and Translational Neurology},
  year = {2026},
  month = nov,
  doi = {10.1002/acn3.70563},
  url = {https://doi.org/10.1002/acn3.70563},
  note = {CC BY-NC-ND 4.0},
}

TY  - JOUR
TI  - Axial Function Reflects Global Severity in Inherited Ataxias: The Upright Stability Score in Ambulatory Friedreich vs. Spinocerebellar Ataxia
AU  - Christian Rummey
AU  - S. H. Subramony
AU  - David R. Lynch
AU  - Louise A. Corben
AU  - Martin B. Delatycki
AU  - Jörg B. Schulz
AU  - Kathrin Reetz
AU  - Massimo Pandolfo
AU  - Matthis Synofzik
AU  - Theresa Zesiewicz
AU  - Antoine Duquette
AU  - Matthew Burns
AU  - Martin Vyhnálek
AU  - Lucie Stovickova
AU  - Sinead M. Murphy
AU  - Petya Bogdanova‐Mihaylova
AU  - Mary Kearney
AU  - Richard Walsh
AU  - Richard H. Roxburgh
AU  - Khalaf Bushara
AU  - Marie Y. Davis
AU  - Enrico S. Bertini
AU  - Gessica Vasco
AU  - Shweta Sahni
AU  - Mohammed Faruq
AU  - Achal K. Srivastava
AU  - Bart van de Warrenburg
AU  - Elisabetta Indelicato
AU  - Sylvia Boesch
AU  - Andrew Billnitzer
AU  - Tetsuo Ashizawa
AU  - Anoopum S. Gupta
AU  - Grace Yoon
AU  - Georgios Koutsis
AU  - Chrysoula Koniari
AU  - Zofia Fleszar
AU  - Christopher M. Gomez
AU  - Andrea Martinuzzi
AU  - Gabriella Paparella
AU  - Ali G. Hamedani
AU  - Puneet Opal
AU  - Rizwan S. Akhtar
AU  - Caterina Mariotti
AU  - Henry Paulson
AU  - Peter Todd
AU  - Sharan R. Srinivasan
AU  - George Wilmot
AU  - Ludger Schöls
AU  - Susan Perlman
AU  - Jeremy D. Schmahmann
AU  - Sheng‐Han Kuo
AU  - Liana S. Rosenthal
AU  - Vikram G. Shakkottai
PY  - 2026
DA  - 2026/11/04
JO  - Annals of Clinical and Translational Neurology
DO  - 10.1002/acn3.70563
UR  - https://doi.org/10.1002/acn3.70563
AB  - Objective: Inherited ataxias are clinically diverse neurodegenerative diseases, complicating the choice of outcome measures for trials. In spinocerebellar ataxia (SCA), regulatory concerns about the Scale for the Assessment and Rating of Ataxia (SARA) caused a shift toward functional SARA (f‐SARA), contributing to pivotal trial failure. We investigated whether the Upright Stability Score (USS), validated in Friedreich ataxia (FRDA), retains its psychometric properties in SCA, and how it compares with SARA, f‐SARA, and the Friedreich Ataxia Activities of Daily Living scale (FA‐ADL).  Methods: Cross‐sectional data from ambulatory participants in two large international natural‐history studies (CRC‐SCA and UNIFAI) were analyzed with correlation‐based psychometric methods, comparing score distributions across scales and genotypes.  Results: Data from 406/343 participants in CRC‐SCA/UNIFAI were analyzed. In SCA, the USS captured a wider spectrum of balance performance, while in FRDA, early proprioceptive deficits—particularly impaired stance with eyes closed—constrained score variability. USS correlated strongly with SARA, f‐SARA, and FA‐ADL in both cohorts. SARA showed moderate skew, and f‐SARA showed pronounced floor effects in mildly affected SCA, whereas USS and FA‐ADL preserved discrimination at the low end. FA‐ADL distributions were broadly comparable across genotypes.  Interpretation: USS showed cross‐sectional convergent validity with established measures across ambulatory FRDA and SCA, reflecting perceived disease burden (FA‐ADL) at least as well as SARA. f‐SARA is poorly discriminating in ambulatory SCA and is unlikely to work as an outcome measure, in particular in early cohorts. USS showed the potential to serve as a primary outcome assessment in pivotal SCA trials, but longitudinal evidence is required. Limitations include cross‐sectional design and a substantial age difference between cohorts.
SN  - 2328-9503
ER  -