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Quantitative Evaluation of Stance as a Sensitive Biomarker of Postural Ataxia Development in Preclinical SCA1 Mutation Carriers

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Abstract

The aim of this study was to determine the time between the first detection of postural control impairments and the evident manifestation of ataxia in preclinical SCA1 individuals. Twenty five preclinical SCA1 mutation carriers: 13 with estimated disease onset ≤ 6 years (SCA1 +) aged 27.8 ± 8.1 years; 12 with expected disease onset > 6 years (SCA1-) aged 26.6 ± 3.1 years and 26 age and sex matched healthy controls (HCs) underwent static posturography during 5 years of observation. The movements of the centre of feet pressure (COP) during quiet standing with eyes open (EO) and closed (EC) were quantified by calculating the mean radius (R), developed surface area (A) and mean COP movement velocity (V). Ataxia was evaluated by use of the Scale for Assessment and Rating of Ataxia (SARA).

SCA1 + exhibited significantly worse quality of stance with EC vs. SCA1- (p < 0.05 for V) and HCs (p < 0.001) even 5 to 6 years before estimated disease onset. There were no statistically significant differences between SCA1- and HCs. A slow increase in Cohen’s d effect size was observed for VEO up to the clinical manifestation of ataxia. VEO and AEC recorded in preclinical SCA1 individuals correlated slightly but statistically significantly with SARA (r = 0.47).

The study confirms that static posturography detects COP sway changes in SCA1 preclinical gene carriers even 5 to 6 years before estimated disease onset. The quantitative evaluation of stance in preclinical SCA is a sensitive biomarker for the monitoring of the disease progression and may be useful in clinical trials.

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Data Availability

The data that support the findings of this study is available from the corresponding author upon reasonable request.

Abbreviations

A :

The center of feet pressure developed surface area

BMI :

Body mass index

CAG :

Cytosine-Adenine-Guanine Triplet

COP :

Center of Feet Pressure

EC :

Eyes Closed

EO :

Eyes Open

HC :

Healthy Controls

INAS :

Inventory of Non-Ataxia Signs

R :

Mean Center of Feet Pressure Sway Radius

SARA :

Scale for Assessment and Rating of Ataxia

SCA :

Spinocerebellar Ataxia

SCA1 :

Spinocerebellar Ataxia Type 1

SCA1 + :

Preclinical SCA1 Mutation carriers Who had ≤ 6 Years-to-Ataxia-Onset

SCA1 - :

Preclinical SCA1 Mutation Carriers who had > 6 Years-to-Ataxia-Onset

V :

The Center of Feet Pressure Mean Velocity

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Acknowledgements

The authors would like to thank all of the patients, their family members and healthy volunteers for their kind cooperation. Anna Sobanska would like to thank dr Beata Sokolowska for tutorials in medical statistics, which enabled her to calculate most of the statistics in this study.

Funding

This article will be available under subscription. The data presented in this publication is a part of an intramural project No 501–061-16038 funded by Polish Ministry of Education.

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Authors and Affiliations

  1. Department of Clinical Neurophysiology, Institute of Psychiatry and Neurology, Warsaw, Poland

    Anna Sobanska

  2. Laboratory of Respiration Physiology, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland

    Leszek Czerwosz

  3. Department of Genetics, Institute of Psychiatry and Neurology, Warsaw, Poland

    Anna Sulek & Iwona Stepniak

  4. Faculty of Medicine, Lazarski University, Warsaw, Poland

    Anna Sulek

  5. Department of Neurology, Military Institute of Aviation Medicine, Warsaw, Poland

    Rafal Rola

  6. First Department of Neurology, Institute of Psychiatry and Neurology, Warsaw, Poland

    Maria Rakowicz

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  1. Anna Sobanska
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Contributions

MR (Maria Rakowicz), LC (Leszek Czerwosz) and ASu (Anna Sulek) had the idea of the study. MR (Maria Rakowicz) was the senior mentor of the study. ASo (Anna Sobanska) performed the most of the tests during the participants’ visits. The remaining tests were done by RR (Rafal Rola), IS (Iwona Stepniak) and MR (Maria Rakowicz). LC (Leszek Czerwosz) and ASo (Anna Sobanska) did statistics. ASo (Anna Sobanska) prepared the draft of the article. LC (Leszek Czerwosz) prepared the figures. All authors reviewed the manuscript. None of the authors stated disapproval of the final version of the article.

Corresponding author

Correspondence to Anna Sobanska.

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Ethical Approval

The study was approved by the Bioethics Committee of the Institute of Psychiatry and Neurology in Warsaw (resolutions 2/2011 and 27/2017). All participants signed a written informed consent before they entered the study.

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The authors declare no competing interests.

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Leszek Czerwosz passed away in May 2023.

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Sobanska, A., Czerwosz, L., Sulek, A. et al. Quantitative Evaluation of Stance as a Sensitive Biomarker of Postural Ataxia Development in Preclinical SCA1 Mutation Carriers. Cerebellum (2024). https://doi.org/10.1007/s12311-024-01679-w

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