{
  "abstract": "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).\n\nMethods: 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.\n\nResults: 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.\n\nInterpretation: 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.",
  "abstract_shown": true,
  "affiliations": [
    "Clinical Data Science GmbH Basel Switzerland",
    "Department of Neurology and Fixel Institute for Neurological Disorders University of Florida College of Medicine Gainesville Florida USA",
    "Department of Neurology The Children's Hospital of Philadelphia Philadelphia Pennsylvania USA",
    "Bruce Lefroy Centre for Genetic Health Research Murdoch Children's Research Institute Parkville Victoria Australia",
    "Department of Paediatrics University of Melbourne Parkville Victoria Australia",
    "Department of Neurology RWTH Aachen University Aachen Germany",
    "JARA‐BRAIN Institute Molecular Neuroscience and Neuroimaging Aachen Germany",
    "Department of Neurology and Neurosurgery McGill University Montreal Quebec Canada",
    "Division Translational Genomics of Neurodegenerative Diseases Hertie‐Institute for Clinical Brain Research Tübingen Germany",
    "German Center for Neurodegenerative Diseases Tübingen Germany",
    "Department of Neurology University of South Florida Tampa Florida USA",
    "Centre Hospitalier de l'Université de Montréal University of Montreal Montreal Quebec Canada",
    "Centre of Hereditary Ataxias, Department of Neurology, Second Faculty of Medicine Charles University, Motol and Homolka University Hospital Prague Czech Republic",
    "Centre of Hereditary Ataxias, Department of Paediatric Neurology, Second Faculty of Medicine Charles University, Motol and Homolka University Hospital Prague Czech Republic",
    "Department of Neurology Tallaght University Hospital Dublin Ireland",
    "Academic Unit of Neurology Trinity College Dublin Dublin Ireland",
    "Centre for Brain Research Neurogenetics Clinic University of Auckland Auckland New Zealand",
    "Department of Neurology University of Minnesota Minneapolis Minnesota USA",
    "Department of Neurology University of Washington Seattle Washington USA",
    "Research Unit of Neuromuscular Disease Ospedale Pediatrico Bambino Gesù, IRCCS Rome Italy",
    "Research Unit of Neurorehabilitation Ospedale Pediatrico Bambino Gesù, IRCCS Rome Italy",
    "Genomics and Molecular Medicine CSIR‐Institute of Genomics and Integrative Biology Delhi India",
    "Department of Neurology Radboud University Medical Center Nijmegen the Netherlands",
    "Neurology Department Innsbruck Medical University Innsbruck Austria",
    "Houston Methodist Research Institute Houston Texas USA",
    "Department of Neurology Massachusetts General Hospital, Harvard Medical School Boston Massachusetts USA",
    "Divisions of Neurology and Clinical and Metabolic Genetics, Department of Paediatrics The Hospital for Sick Children, University of Toronto Toronto Canada",
    "1st Department of Neurology Eginition Hospital, National and Kapodistrian University of Athens Athens Greece",
    "Department of Neurology and Hertie Institute for Clinical Brain Research University of Tübingen Tübingen Germany",
    "Department of Neurology University of Chicago Chicago Illinois USA",
    "IRCCS E. Medea Conegliano Italy",
    "Department of Neurology Perelman School of Medicine, University of Pennsylvania Philadelphia Pennsylvania USA",
    "Department of Neurology Northwestern University Chicago Illinois USA",
    "Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Istituto Neurologico Carlo Besta Milano Italy",
    "Department of Neurology University of Michigan Ann Arbor Michigan USA",
    "Department of Neurology Emory University Atlanta Georgia USA",
    "Department of Neurology University of California Los Angeles Los Angeles California USA",
    "Department of Neurology Columbia University Irving Medical Center and the New York Presbyterian Hospital New York New York USA",
    "Initiative for Columbia Ataxia and Tremor Columbia University Irving Medical Center New York New York USA",
    "Department of Neurology Johns Hopkins School of Medicine Baltimore Maryland USA"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 53,
  "authors": [
    {
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        0
      ],
      "name": "Christian Rummey",
      "orcid": "0000-0003-4911-911X"
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        1
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      "name": "S. H. Subramony",
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        4
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      "name": "Louise A. Corben"
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        3,
        4
      ],
      "name": "Martin B. Delatycki"
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        5,
        6
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      "name": "Jörg B. Schulz",
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      "name": "Matthew Burns"
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      "name": "Sinead M. Murphy"
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      "name": "Petya Bogdanova‐Mihaylova"
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      "name": "Mary Kearney",
      "orcid": "0009-0009-4627-537X"
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      "name": "Richard Walsh"
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      "name": "Richard H. Roxburgh"
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      "name": "Khalaf Bushara"
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      "name": "Marie Y. Davis"
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      ],
      "name": "Enrico S. Bertini"
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      ],
      "name": "Gessica Vasco"
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      "affs": [
        21
      ],
      "name": "Shweta Sahni"
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    {
      "affs": [
        21
      ],
      "name": "Mohammed Faruq"
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    {
      "affs": [
        21
      ],
      "name": "Achal K. Srivastava",
      "orcid": "0000-0002-4590-7947"
    },
    {
      "affs": [
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      ],
      "name": "Bart van de Warrenburg"
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      "name": "Elisabetta Indelicato",
      "orcid": "0000-0003-0217-8630"
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      "name": "Sylvia Boesch"
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      ],
      "name": "Andrew Billnitzer"
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    {
      "affs": [
        24
      ],
      "name": "Tetsuo Ashizawa"
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      "affs": [
        25
      ],
      "name": "Anoopum S. Gupta"
    },
    {
      "affs": [
        26
      ],
      "name": "Grace Yoon",
      "orcid": "0000-0002-0415-4416"
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    {
      "affs": [
        27
      ],
      "name": "Georgios Koutsis"
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    {
      "affs": [
        27
      ],
      "name": "Chrysoula Koniari"
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    {
      "affs": [
        28
      ],
      "name": "Zofia Fleszar"
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    {
      "affs": [
        29
      ],
      "name": "Christopher M. Gomez"
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    {
      "affs": [
        30
      ],
      "name": "Andrea Martinuzzi"
    },
    {
      "affs": [
        30
      ],
      "name": "Gabriella Paparella"
    },
    {
      "affs": [
        31
      ],
      "name": "Ali G. Hamedani",
      "orcid": "0000-0001-5949-6395"
    },
    {
      "affs": [
        32
      ],
      "name": "Puneet Opal",
      "orcid": "0000-0001-9110-2202"
    },
    {
      "affs": [
        32
      ],
      "name": "Rizwan S. Akhtar",
      "orcid": "0000-0001-9808-7228"
    },
    {
      "affs": [
        33
      ],
      "name": "Caterina Mariotti",
      "orcid": "0000-0003-2405-3564"
    },
    {
      "affs": [
        34
      ],
      "name": "Henry Paulson",
      "orcid": "0000-0002-0382-7535"
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    {
      "affs": [
        34
      ],
      "name": "Peter Todd"
    },
    {
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        34
      ],
      "name": "Sharan R. Srinivasan",
      "orcid": "0000-0003-2729-6625"
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        35
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      "name": "George Wilmot"
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        9,
        28
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      "name": "Ludger Schöls"
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      "name": "Susan Perlman"
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        25
      ],
      "name": "Jeremy D. Schmahmann"
    },
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        37,
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      ],
      "name": "Sheng‐Han Kuo",
      "orcid": "0000-0002-9412-931X"
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      "affs": [
        39
      ],
      "name": "Liana S. Rosenthal"
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      "name": "Vikram G. Shakkottai",
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  "bibtex": "https://research.draconitic.com/paper/16501ffe5trhc.bib",
  "cited_by": 0,
  "doi": "10.1002/acn3.70563",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13736190/",
  "id": "16501ffe5trhc",
  "issns": [
    "2328-9503"
  ],
  "landing_url": "https://doi.org/10.1002/acn3.70563",
  "language": "en",
  "licence": "CC-BY-NC-ND-4.0",
  "licence_label": "CC BY-NC-ND 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Research Article"
    ],
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      "openalex",
      "2804|Genetic Neurodegenerative Diseases"
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  "openalex": "W7225348305",
  "pdf_url": "https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/acn3.70563",
  "pmcid": "PMC13736190",
  "pmid": "42984128",
  "published": "2026-11-04",
  "publisher": "Wiley",
  "ris": "https://research.draconitic.com/paper/16501ffe5trhc.ris",
  "sources": [
    {
      "first_seen": "2026-11-09T12:21:42Z",
      "native_id": "PMC13736190",
      "source": "pmc",
      "url": "https://doi.org/10.1002/acn3.70563"
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  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2804|Genetic Neurodegenerative Diseases",
      "subfield": "neuroscience"
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  ],
  "title": "Axial Function Reflects Global Severity in Inherited Ataxias: The Upright Stability Score in Ambulatory Friedreich vs. Spinocerebellar Ataxia",
  "title_text": "Axial Function Reflects Global Severity in Inherited Ataxias: The Upright Stability Score in Ambulatory Friedreich vs. Spinocerebellar Ataxia",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T12:21:42Z",
  "url": "https://research.draconitic.com/paper/16501ffe5trhc",
  "venue": "Annals of Clinical and Translational Neurology",
  "versions": []
}