Longitudinal changes of SARA scale in Friedreich ataxia: Strong influence of baseline score and age at onset

Luca Porcu ¹, Mario Fichera ², Lorenzo Nanetti ²

¹Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK.
²Unit of Medical Genetics and Neurogenetics, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, 20133, Italy.
³Laboratory of Methodology for Clinical Research, Oncology Department, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy.
⁴Department of Clinical and Movement Neurosciences, Ataxia Centre, UCL-Queen Square Institute of Neurology, London, WC1N 3BG, UK.
⁵Sorbonne Université, Paris Brain Institute (ICM Institut du Cerveau), AP-HP, INSERM, CNRS, University Hospital Pitié-Salpêtrière, Paris, 75646, France.
⁶Department of Neurology, Medical University Innsbruck, Innsbruck, 6020, Austria.
⁷Department of Neurology, Friedrich Baur Institute, University Hospital, LMU, Munich, 80336, Germany.
⁸German Center for Neurodegenerative Diseases (DZNE), Munich, 81377, Germany.
⁹Munich Cluster for Systems Neurology (SyNergy), Munich, 81377, Germany.
¹⁰Reference Unit of Hereditary Ataxias and Paraplegias, Department of Neurology, IdiPAZ, Hospital Universitario La Paz, Madrid, 28046, Spain.
¹¹Department of Neurology and Hertie-Institute for Clinical Brain Research, University of Tübingen, Tübingen, 72076, Germany.
¹²German Center for Neurodegenerative Diseases (DZNE), Tübingen, 72076, Germany.
¹³Department of Neurology, University Hospital of Bonn, Bonn, 53127, Germany.
¹⁴Department of Neurology, RWTH Aachen University, Aachen, 52074, Germany.
¹⁵Laboratory of Experimental Neurology, Université Libre de Bruxelles, Brussels, 1070, Belgium.
¹⁶German Center for Neurodegenerative Diseases (DZNE), Bonn, 53127, Germany.
¹⁷Department of Neurology and Neurosurgery, McGill University, Montreal, QC, H3A 0G4, Canada.
¹⁸JARA Brain Institute Molecular Neuroscience and Neuroimaging, Research Centre Jülich and RWTH Aachen University, Aachen, 52056, Germany.

⁰Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK.

Annals of Clinical and Translational Neurology +

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August 29, 2023

View abstract on PubMed

Summary

The Scale for Assessment and Rating of Ataxia (SARA) shows variable sensitivity in Friedreich ataxia (FA) patients. Gait progression is the fastest, informing clinical trial design.

Area Of Science

Neurology
Clinical Trials
Biostatistics

Background

The Scale for Assessment and Rating of Ataxia (SARA) is a key outcome measure in Friedreich ataxia (FA) research.
SARA is utilized in the European natural history study for FA, a progressive neurodegenerative disorder.

Purpose Of The Study

To analyze the distribution and longitudinal changes of SARA scores and individual items in typical-onset FA.
To understand the pattern and rate of disease progression using SARA in a large patient cohort.

Main Methods

Analysis of SARA scores from 502 typical-onset FA patients in the 4-year prospective EFACTS study.
Linear mixed-effects regression models were used to determine disease progression patterns.
Kaplan-Meier method and weighted linear regression estimated time-to-change and score progression rates.

Main Results

SARA score at enrollment and age at onset were primary predictors of total score progression over 4 years.
Gait item showed the highest annual progression rate, with a one-point increase every 1-2 years.
Disease duration did not significantly improve the prediction model, unlike age at evaluation.

Conclusions

SARA's sensitivity varies across different disease stages in FA.
Findings provide crucial data for selecting patient populations and interpreting results in future FA clinical trials.
Understanding SARA's performance aids in optimizing trial design and outcome assessment for ataxias.

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