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Spinocerebellar Ataxia Type 1: One-Year Longitudinal Study to Identify Clinical and MRI Measures of Disease Progression in Patients and Presymptomatic Carriers

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Abstract

Spinocerebellar ataxias type 1 (SCA1) is an autosomal dominant disease usually manifesting in adulthood. We performed a prospective 1-year longitudinal study in 14 presymptomatic mutation carriers (preSCA1), 11 ataxic patients, and 21 healthy controls. SCA1 patients had a median disease duration of 6 years (range 2–16) and SARA score of 7 points (range 3.5–20). PreSCA1 had an estimated time before disease onset of 9.7 years (range 4–30), and no signs of ataxia. At baseline, SCA1 patients significantly differed from controls in SARA score (Scale for Assessment and Rating of Ataxia), cognitive tests, and structural MRI measures. Significant volume loss was found in cerebellum, brainstem, basal ganglia, and cortical thinning in frontal, temporal, and occipital regions. PreSCA1 did not differ from controls. At 1-year follow-up, SCA1 patients showed significant increase in SARA score, and decreased volume of cerebellum (− 0.6%), pons (− 5.5%), superior cerebellar peduncles (− 10.7%), and midbrain (− 3.0%). Signs of disease progression were also observed in preSCA1 subjects, with increased SARA score and reduced total cerebellar volume. Our exploratory study suggests that clinical scores and MRI measures provide valuable data to monitor and quantify the earliest changes associated with the preclinical and the symptomatic phases of SCA1 disease.

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The raw data supporting the conclusions of this article will be made available by the authors, upon specific request.

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Acknowledgements

We would like to thank all participants and their families for taking part in our study. The study was supported by the Italian Ministry of Health (Grant RF-2011-02347420 to CM).

Several authors (LN; FT; CM) of this publication are members of the European Reference Network for Rare Neurological Diseases, project ID no. 739510.

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Author notes

  1. Anna Nigri and Lidia Sarro contributed equally to the manuscript.

Authors and Affiliations

  1. Neuroradiology, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy

    Anna Nigri, Chiara Pinardi, Marina Grisoli, Stefania Ferraro & Maria Grazia Bruzzone

  2. Medical Genetics and Neurogenetics, Fondazione IRCCS Istituto Neurologico Carlo Besta, via Celoria 11, 20133, Milan, Italy

    Lidia Sarro, Alessia Mongelli, Anna Castaldo, Lorenzo Nanetti, Franco Taroni & Caterina Mariotti

  3. Neurology Unit, Martini Hospital, Turin, Italy

    Lidia Sarro

  4. Methodology for Clinical Research Laboratory, Oncology Department, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy

    Luca Porcu

  5. Neurophysiology, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy

    Laura Canafoglia & Elisa Visani

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Contributions

A. Nigri, L, Sarro, C. Mariotti: study design, conception, execution, writing of the draft, and review manuscript. A. Mongelli, A. Castaldo, L. Nanetti, C. Pinardi, S.a Ferraro, E. Visani, M. Grisoli, L. Canafoglia, MG. Bruzzone, F. Taroni: conception, execution, writing of the draft. L. Porcu: statistical analyses, writing of the draft, and review manuscript.

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Correspondence to Caterina Mariotti.

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CM reports personal fees from Roche and grant from Italian Ministry of Health; AN; LS; AM;AC; LP; CP; MG; SF; LC; EV; MGB; LN; and FT declare no competing interests.

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Nigri, A., Sarro, L., Mongelli, A. et al. Spinocerebellar Ataxia Type 1: One-Year Longitudinal Study to Identify Clinical and MRI Measures of Disease Progression in Patients and Presymptomatic Carriers. Cerebellum 21, 133–144 (2022). https://doi.org/10.1007/s12311-021-01285-0

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