Long-term disease progression in spinocerebellar ataxia types 1, 2, 3, and 6: A longitudinal cohort study

Heike Jacobi, Sophie Tezenas du Montcel, Peter Bauer, Paola Giunti, Arron Cook, Robyn Labrum, Michael H. Parkinson, Alexandra Durr, Alexis Brice, Perrine Charles, Cecilia Marelli, Caterina Mariotti, Lorenzo Nanetti, Marta Panzeri, Maria Rakowicz, Anna Sulek, Anna Sobanska, Tanja Schmitz-Hübsch, Ludger Schöls, Holger HengelL. Balikó, B. Melegh, Alessandro Filla, Antonella Antenora, Jon Infante, José Berciano, Bart P. van de Warrenburg, Dagmar Timmann, Sandra Szymanski, Sylvia Boesch, Jun Suk Kang, Massimo Pandolfo, Jörg B. Schulz, Sonia Molho, Alhassane Diallo, Thomas Klockgether

Research output: Article

68 Citations (Scopus)

Abstract

Background: Spinocerebellar ataxias are dominantly inherited neurodegenerative diseases. As potential treatments for these diseases are being developed, precise knowledge of their natural history is needed. We aimed to study the long-term disease progression of the most common spinocerebellar ataxias: SCA1, SCA2, SCA3, and SCA6. Furthermore, we aimed to establish the order and occurrence of non-ataxia symptoms, and identify predictors of disease progression. Methods: In this longitudinal cohort study (EUROSCA), we enrolled men and women with positive genetic testing for SCA1, SCA2, SCA3, or SCA6 and with progressive, otherwise unexplained ataxia who were aged 18 years or older from 17 ataxia referral centres in ten European countries. Patients were seen every year for 3 years, and at irregular intervals thereafter. The primary outcome was the scale for the assessment and rating of ataxia (SARA), and the inventory of non-ataxia signs (INAS). We used linear mixed models to analyse progression. To account for dropouts, we applied a pattern-mixture model. This study is registered with ClinicalTrials.gov, number NCT02440763. Findings: Between July 1, 2005, and Aug 31, 2006, 526 patients with SCA1, SCA2, SCA3, or SCA6 were enrolled. We analysed data for 462 patients with at least one follow-up visit. Median observation time was 49 months (IQR 35-72). SARA progression data were best fitted with a linear model in all genotypes. Annual SARA score increase was 2.11 (SE 0.12) in patients with SCA1, 1.49 (0.07) in patients with SCA2, 1.56 (0.08) in patients with SCA3, and 0.80 (0.09) in patients with SCA6. The increase of the number of non-ataxia signs reached a plateau in SCA1, SCA2, and SCA3. In patients with SCA6, the number of non-ataxia symptoms increased linearly, but more slowly than in patients with SCA1, SCA2, and SCA3 (p

Original languageEnglish
Article number147
Pages (from-to)1101-1108
Number of pages8
JournalThe Lancet Neurology
Volume14
Issue number11
DOIs
Publication statusPublished - nov. 1 2015

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Spinocerebellar Ataxias
Longitudinal Studies
Disease Progression
Cohort Studies
Ataxia
Linear Models
Genetic Testing
Natural History
Neurodegenerative Diseases
Referral and Consultation
Genotype
Observation
Equipment and Supplies

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Jacobi, H., du Montcel, S. T., Bauer, P., Giunti, P., Cook, A., Labrum, R., ... Klockgether, T. (2015). Long-term disease progression in spinocerebellar ataxia types 1, 2, 3, and 6: A longitudinal cohort study. The Lancet Neurology, 14(11), 1101-1108. [147]. https://doi.org/10.1016/S1474-4422(15)00202-1

Long-term disease progression in spinocerebellar ataxia types 1, 2, 3, and 6 : A longitudinal cohort study. / Jacobi, Heike; du Montcel, Sophie Tezenas; Bauer, Peter; Giunti, Paola; Cook, Arron; Labrum, Robyn; Parkinson, Michael H.; Durr, Alexandra; Brice, Alexis; Charles, Perrine; Marelli, Cecilia; Mariotti, Caterina; Nanetti, Lorenzo; Panzeri, Marta; Rakowicz, Maria; Sulek, Anna; Sobanska, Anna; Schmitz-Hübsch, Tanja; Schöls, Ludger; Hengel, Holger; Balikó, L.; Melegh, B.; Filla, Alessandro; Antenora, Antonella; Infante, Jon; Berciano, José; van de Warrenburg, Bart P.; Timmann, Dagmar; Szymanski, Sandra; Boesch, Sylvia; Kang, Jun Suk; Pandolfo, Massimo; Schulz, Jörg B.; Molho, Sonia; Diallo, Alhassane; Klockgether, Thomas.

In: The Lancet Neurology, Vol. 14, No. 11, 147, 01.11.2015, p. 1101-1108.

Research output: Article

Jacobi, H, du Montcel, ST, Bauer, P, Giunti, P, Cook, A, Labrum, R, Parkinson, MH, Durr, A, Brice, A, Charles, P, Marelli, C, Mariotti, C, Nanetti, L, Panzeri, M, Rakowicz, M, Sulek, A, Sobanska, A, Schmitz-Hübsch, T, Schöls, L, Hengel, H, Balikó, L, Melegh, B, Filla, A, Antenora, A, Infante, J, Berciano, J, van de Warrenburg, BP, Timmann, D, Szymanski, S, Boesch, S, Kang, JS, Pandolfo, M, Schulz, JB, Molho, S, Diallo, A & Klockgether, T 2015, 'Long-term disease progression in spinocerebellar ataxia types 1, 2, 3, and 6: A longitudinal cohort study', The Lancet Neurology, vol. 14, no. 11, 147, pp. 1101-1108. https://doi.org/10.1016/S1474-4422(15)00202-1
Jacobi, Heike ; du Montcel, Sophie Tezenas ; Bauer, Peter ; Giunti, Paola ; Cook, Arron ; Labrum, Robyn ; Parkinson, Michael H. ; Durr, Alexandra ; Brice, Alexis ; Charles, Perrine ; Marelli, Cecilia ; Mariotti, Caterina ; Nanetti, Lorenzo ; Panzeri, Marta ; Rakowicz, Maria ; Sulek, Anna ; Sobanska, Anna ; Schmitz-Hübsch, Tanja ; Schöls, Ludger ; Hengel, Holger ; Balikó, L. ; Melegh, B. ; Filla, Alessandro ; Antenora, Antonella ; Infante, Jon ; Berciano, José ; van de Warrenburg, Bart P. ; Timmann, Dagmar ; Szymanski, Sandra ; Boesch, Sylvia ; Kang, Jun Suk ; Pandolfo, Massimo ; Schulz, Jörg B. ; Molho, Sonia ; Diallo, Alhassane ; Klockgether, Thomas. / Long-term disease progression in spinocerebellar ataxia types 1, 2, 3, and 6 : A longitudinal cohort study. In: The Lancet Neurology. 2015 ; Vol. 14, No. 11. pp. 1101-1108.
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abstract = "Background: Spinocerebellar ataxias are dominantly inherited neurodegenerative diseases. As potential treatments for these diseases are being developed, precise knowledge of their natural history is needed. We aimed to study the long-term disease progression of the most common spinocerebellar ataxias: SCA1, SCA2, SCA3, and SCA6. Furthermore, we aimed to establish the order and occurrence of non-ataxia symptoms, and identify predictors of disease progression. Methods: In this longitudinal cohort study (EUROSCA), we enrolled men and women with positive genetic testing for SCA1, SCA2, SCA3, or SCA6 and with progressive, otherwise unexplained ataxia who were aged 18 years or older from 17 ataxia referral centres in ten European countries. Patients were seen every year for 3 years, and at irregular intervals thereafter. The primary outcome was the scale for the assessment and rating of ataxia (SARA), and the inventory of non-ataxia signs (INAS). We used linear mixed models to analyse progression. To account for dropouts, we applied a pattern-mixture model. This study is registered with ClinicalTrials.gov, number NCT02440763. Findings: Between July 1, 2005, and Aug 31, 2006, 526 patients with SCA1, SCA2, SCA3, or SCA6 were enrolled. We analysed data for 462 patients with at least one follow-up visit. Median observation time was 49 months (IQR 35-72). SARA progression data were best fitted with a linear model in all genotypes. Annual SARA score increase was 2.11 (SE 0.12) in patients with SCA1, 1.49 (0.07) in patients with SCA2, 1.56 (0.08) in patients with SCA3, and 0.80 (0.09) in patients with SCA6. The increase of the number of non-ataxia signs reached a plateau in SCA1, SCA2, and SCA3. In patients with SCA6, the number of non-ataxia symptoms increased linearly, but more slowly than in patients with SCA1, SCA2, and SCA3 (p",
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T1 - Long-term disease progression in spinocerebellar ataxia types 1, 2, 3, and 6

T2 - A longitudinal cohort study

AU - Jacobi, Heike

AU - du Montcel, Sophie Tezenas

AU - Bauer, Peter

AU - Giunti, Paola

AU - Cook, Arron

AU - Labrum, Robyn

AU - Parkinson, Michael H.

AU - Durr, Alexandra

AU - Brice, Alexis

AU - Charles, Perrine

AU - Marelli, Cecilia

AU - Mariotti, Caterina

AU - Nanetti, Lorenzo

AU - Panzeri, Marta

AU - Rakowicz, Maria

AU - Sulek, Anna

AU - Sobanska, Anna

AU - Schmitz-Hübsch, Tanja

AU - Schöls, Ludger

AU - Hengel, Holger

AU - Balikó, L.

AU - Melegh, B.

AU - Filla, Alessandro

AU - Antenora, Antonella

AU - Infante, Jon

AU - Berciano, José

AU - van de Warrenburg, Bart P.

AU - Timmann, Dagmar

AU - Szymanski, Sandra

AU - Boesch, Sylvia

AU - Kang, Jun Suk

AU - Pandolfo, Massimo

AU - Schulz, Jörg B.

AU - Molho, Sonia

AU - Diallo, Alhassane

AU - Klockgether, Thomas

PY - 2015/11/1

Y1 - 2015/11/1

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