Friedreich and dominant ataxias: Quantitative differences in cerebellar dysfunction measurements

Audrey Tanguy Melac, Caterina Mariotti, Antoine Filipovic Pierucci, Paola Giunti, Javier Arpa, Sylvia Boesch, Thomas Klopstock, Jennifer Müller Vom Hagen, Thomas Klockgether, Katrin Bürk, Jörg B. Schulz, Kathrin Reetz, Massimo Pandolfo, Alexandra Durr, Sophie Tezenas Du Montcel, M. Panzeri, M. H. Parkinson, I. Sanz-Gallego, W. Nachbauer, I. KarinC. Depondt, L. Schoels, I. Giordano, L. Nanetti, A. Castaldo, A. Eigentler

Research output: Contribution to journalArticle

Abstract

Background: Sensitive outcome measures for clinical trials on cerebellar ataxias are lacking. Most cerebellar ataxias progress very slowly and quantitative measurements are required to evaluate cerebellar dysfunction. Methods: We evaluated two scales for rating cerebellar ataxias: the Composite Cerebellar Functional Severity (CCFS) Scale and Scale for the Assessment and Rating of Ataxia (SARA), in patients with spinocerebellar ataxia (SCA) and controls. We evaluated these scales for different diseases and investigated the factors governing the scores obtained. All patients were recruited prospectively. Results: There were 383 patients with Friedreich's ataxia (FRDA), 205 patients with SCA and 168 controls. In FRDA, 31% of the variance of cerebellar signs with the CCFS and 41% of that with SARA were explained by disease duration, age at onset and the shorter abnormal repeat in the FXN gene. Increases in CCFS and SARA scores per year were lower for FRDA than for SCA (CCFS index: 0.123±0.123 per year vs 0.163±0.179, P<0.001; SARA index: 1.5±1.2 vs 1.7±1.7, P<0.001), indicating slower cerebellar dysfunction indexes for FRDA than for SCA. Patients with SCA2 had higher CCFS scores than patients with SCA1 and SCA3, but similar SARA scores. Conclusions: Cerebellar dysfunction, as measured with the CCFS and SARA scales, was more severe in FRDA than in patients with SCA, but with lower progression indexes, within the limits of these types of indexes. Ceiling effects may occur at late stages, for both scales. The CCFS scale is rater-independent and could be used in a multicentre context, as it is simple, rapid and fully automated.

Original languageEnglish
Pages (from-to)559-565
Number of pages7
JournalJournal of Neurology, Neurosurgery and Psychiatry
Volume89
Issue number6
DOIs
Publication statusPublished - Jun 1 2018

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Friedreich Ataxia
Cerebellar Diseases
Spinocerebellar Ataxias
Ataxia
Cerebellar Ataxia
Age of Onset
Outcome Assessment (Health Care)
Clinical Trials

ASJC Scopus subject areas

  • Surgery
  • Clinical Neurology
  • Psychiatry and Mental health

Cite this

Friedreich and dominant ataxias : Quantitative differences in cerebellar dysfunction measurements. / Melac, Audrey Tanguy; Mariotti, Caterina; Pierucci, Antoine Filipovic; Giunti, Paola; Arpa, Javier; Boesch, Sylvia; Klopstock, Thomas; Vom Hagen, Jennifer Müller; Klockgether, Thomas; Bürk, Katrin; Schulz, Jörg B.; Reetz, Kathrin; Pandolfo, Massimo; Durr, Alexandra; Du Montcel, Sophie Tezenas; Panzeri, M.; Parkinson, M. H.; Sanz-Gallego, I.; Nachbauer, W.; Karin, I.; Depondt, C.; Schoels, L.; Giordano, I.; Nanetti, L.; Castaldo, A.; Eigentler, A.

In: Journal of Neurology, Neurosurgery and Psychiatry, Vol. 89, No. 6, 01.06.2018, p. 559-565.

Research output: Contribution to journalArticle

Melac, AT, Mariotti, C, Pierucci, AF, Giunti, P, Arpa, J, Boesch, S, Klopstock, T, Vom Hagen, JM, Klockgether, T, Bürk, K, Schulz, JB, Reetz, K, Pandolfo, M, Durr, A, Du Montcel, ST, Panzeri, M, Parkinson, MH, Sanz-Gallego, I, Nachbauer, W, Karin, I, Depondt, C, Schoels, L, Giordano, I, Nanetti, L, Castaldo, A & Eigentler, A 2018, 'Friedreich and dominant ataxias: Quantitative differences in cerebellar dysfunction measurements', Journal of Neurology, Neurosurgery and Psychiatry, vol. 89, no. 6, pp. 559-565. https://doi.org/10.1136/jnnp-2017-316964
Melac, Audrey Tanguy ; Mariotti, Caterina ; Pierucci, Antoine Filipovic ; Giunti, Paola ; Arpa, Javier ; Boesch, Sylvia ; Klopstock, Thomas ; Vom Hagen, Jennifer Müller ; Klockgether, Thomas ; Bürk, Katrin ; Schulz, Jörg B. ; Reetz, Kathrin ; Pandolfo, Massimo ; Durr, Alexandra ; Du Montcel, Sophie Tezenas ; Panzeri, M. ; Parkinson, M. H. ; Sanz-Gallego, I. ; Nachbauer, W. ; Karin, I. ; Depondt, C. ; Schoels, L. ; Giordano, I. ; Nanetti, L. ; Castaldo, A. ; Eigentler, A. / Friedreich and dominant ataxias : Quantitative differences in cerebellar dysfunction measurements. In: Journal of Neurology, Neurosurgery and Psychiatry. 2018 ; Vol. 89, No. 6. pp. 559-565.
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abstract = "Background: Sensitive outcome measures for clinical trials on cerebellar ataxias are lacking. Most cerebellar ataxias progress very slowly and quantitative measurements are required to evaluate cerebellar dysfunction. Methods: We evaluated two scales for rating cerebellar ataxias: the Composite Cerebellar Functional Severity (CCFS) Scale and Scale for the Assessment and Rating of Ataxia (SARA), in patients with spinocerebellar ataxia (SCA) and controls. We evaluated these scales for different diseases and investigated the factors governing the scores obtained. All patients were recruited prospectively. Results: There were 383 patients with Friedreich's ataxia (FRDA), 205 patients with SCA and 168 controls. In FRDA, 31{\%} of the variance of cerebellar signs with the CCFS and 41{\%} of that with SARA were explained by disease duration, age at onset and the shorter abnormal repeat in the FXN gene. Increases in CCFS and SARA scores per year were lower for FRDA than for SCA (CCFS index: 0.123±0.123 per year vs 0.163±0.179, P<0.001; SARA index: 1.5±1.2 vs 1.7±1.7, P<0.001), indicating slower cerebellar dysfunction indexes for FRDA than for SCA. Patients with SCA2 had higher CCFS scores than patients with SCA1 and SCA3, but similar SARA scores. Conclusions: Cerebellar dysfunction, as measured with the CCFS and SARA scales, was more severe in FRDA than in patients with SCA, but with lower progression indexes, within the limits of these types of indexes. Ceiling effects may occur at late stages, for both scales. The CCFS scale is rater-independent and could be used in a multicentre context, as it is simple, rapid and fully automated.",
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T1 - Friedreich and dominant ataxias

T2 - Quantitative differences in cerebellar dysfunction measurements

AU - Melac, Audrey Tanguy

AU - Mariotti, Caterina

AU - Pierucci, Antoine Filipovic

AU - Giunti, Paola

AU - Arpa, Javier

AU - Boesch, Sylvia

AU - Klopstock, Thomas

AU - Vom Hagen, Jennifer Müller

AU - Klockgether, Thomas

AU - Bürk, Katrin

AU - Schulz, Jörg B.

AU - Reetz, Kathrin

AU - Pandolfo, Massimo

AU - Durr, Alexandra

AU - Du Montcel, Sophie Tezenas

AU - Panzeri, M.

AU - Parkinson, M. H.

AU - Sanz-Gallego, I.

AU - Nachbauer, W.

AU - Karin, I.

AU - Depondt, C.

AU - Schoels, L.

AU - Giordano, I.

AU - Nanetti, L.

AU - Castaldo, A.

AU - Eigentler, A.

PY - 2018/6/1

Y1 - 2018/6/1

N2 - Background: Sensitive outcome measures for clinical trials on cerebellar ataxias are lacking. Most cerebellar ataxias progress very slowly and quantitative measurements are required to evaluate cerebellar dysfunction. Methods: We evaluated two scales for rating cerebellar ataxias: the Composite Cerebellar Functional Severity (CCFS) Scale and Scale for the Assessment and Rating of Ataxia (SARA), in patients with spinocerebellar ataxia (SCA) and controls. We evaluated these scales for different diseases and investigated the factors governing the scores obtained. All patients were recruited prospectively. Results: There were 383 patients with Friedreich's ataxia (FRDA), 205 patients with SCA and 168 controls. In FRDA, 31% of the variance of cerebellar signs with the CCFS and 41% of that with SARA were explained by disease duration, age at onset and the shorter abnormal repeat in the FXN gene. Increases in CCFS and SARA scores per year were lower for FRDA than for SCA (CCFS index: 0.123±0.123 per year vs 0.163±0.179, P<0.001; SARA index: 1.5±1.2 vs 1.7±1.7, P<0.001), indicating slower cerebellar dysfunction indexes for FRDA than for SCA. Patients with SCA2 had higher CCFS scores than patients with SCA1 and SCA3, but similar SARA scores. Conclusions: Cerebellar dysfunction, as measured with the CCFS and SARA scales, was more severe in FRDA than in patients with SCA, but with lower progression indexes, within the limits of these types of indexes. Ceiling effects may occur at late stages, for both scales. The CCFS scale is rater-independent and could be used in a multicentre context, as it is simple, rapid and fully automated.

AB - Background: Sensitive outcome measures for clinical trials on cerebellar ataxias are lacking. Most cerebellar ataxias progress very slowly and quantitative measurements are required to evaluate cerebellar dysfunction. Methods: We evaluated two scales for rating cerebellar ataxias: the Composite Cerebellar Functional Severity (CCFS) Scale and Scale for the Assessment and Rating of Ataxia (SARA), in patients with spinocerebellar ataxia (SCA) and controls. We evaluated these scales for different diseases and investigated the factors governing the scores obtained. All patients were recruited prospectively. Results: There were 383 patients with Friedreich's ataxia (FRDA), 205 patients with SCA and 168 controls. In FRDA, 31% of the variance of cerebellar signs with the CCFS and 41% of that with SARA were explained by disease duration, age at onset and the shorter abnormal repeat in the FXN gene. Increases in CCFS and SARA scores per year were lower for FRDA than for SCA (CCFS index: 0.123±0.123 per year vs 0.163±0.179, P<0.001; SARA index: 1.5±1.2 vs 1.7±1.7, P<0.001), indicating slower cerebellar dysfunction indexes for FRDA than for SCA. Patients with SCA2 had higher CCFS scores than patients with SCA1 and SCA3, but similar SARA scores. Conclusions: Cerebellar dysfunction, as measured with the CCFS and SARA scales, was more severe in FRDA than in patients with SCA, but with lower progression indexes, within the limits of these types of indexes. Ceiling effects may occur at late stages, for both scales. The CCFS scale is rater-independent and could be used in a multicentre context, as it is simple, rapid and fully automated.

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