Abstract
We aimed to perform a comprehensive systematic review of the existing ataxia scales. We described the disorders for which the instruments have been validated and used, the time spent in its application, its validated psychometric properties, and their use in studies of natural history and clinical trials. A search from 1997 onwards was performed in the MEDLINE, LILACS, and Cochrane databases. The web sites ClinicalTrials.gov and Orpha.net were also used to identify the endpoints used in ongoing randomized clinical trials. We identified and described the semiquantitative ataxia scales (ICARS, SARA, MICARS, BARS); semiquantitative ataxia and non-ataxia scales (UMSARS, FARS, NESSCA); a semiquantitative non-ataxia scale (INAS); quantitative ataxia scales (CATSYS 2000, AFCS, CCFS and CCFSw, and SCAFI); and the self-performed ataxia scale (FAIS). SARA and ICARS were the best studied and validated so far, and their reliability sustain their use. Ataxia and non-ataxia scores will probably provide a better view of the overall disability in long-term trials and studies of natural history. Up to now, no clear advantage has been disclosed for any of them; however, we recommend the use of specific measurements of gait since gait ataxia is the first significant manifestation in the majority of ataxia disorders and comment on the best scales to be used in specific ataxia forms. Quantitative ataxia scales will be needed to speed up evidence from phase II clinical trials, from trials focused on the early phase of diseases, and for secondary endpoints in phase III trials. Finally, it is worth remembering that estimation of the actual minimal clinically relevant difference is still lacking; this, together with changes in quality of life, will probably be the main endpoints to measure in future therapeutic studies.
Similar content being viewed by others
References
Klockgether T. Sporadic ataxia with adult onset: classification and diagnostic criteria. Lancet Neurol. 2010;9:94–104.
Kieling C, Morales Saute JA, Jardim LB. When ataxia is not just ataxia. Nat Clin Pract Neurol. 2007;3:E2.
Trouillas P, Takayanagi T, Hallett M, Currier RD, Subramony SH, Wessel K, et al. International Cooperative Ataxia Rating Scale for pharmacological assessment of the cerebellar syndrome. The Ataxia Neuropharmacology Committee of the World Federation of Neurology. J Neurol Sci. 1997;145:205–11.
Tison F, Yekhlef F, Balestre E, Chrysostome V, Quinn N, Wenning, et al. Application of the International Cooperative Ataxia Scale rating in multiple system atrophy. Mov Disord. 2002;17:1248–54.
Storey E, Tuck K, Hester R, Hughes A, Churchyard A. Inter-rater reliability of the International Cooperative Ataxia Rating Scale (ICARS). Mov Disord. 2004;19:190–2.
Schmitz-Hübsch T, Tezenas du Montcel S, Baliko L, Boesch S, Bonato S, Fancellu R, et al. Reliability and validity of the International Cooperative Ataxia Rating Scale: a study in 156 spinocerebellar ataxia patients. Mov Disord. 2006;21:699–704.
D’Abreu A, Franca Jr M, Lopes-Cendes I, Cendes F. The international cooperative ataxia rating scale in Machado–Joseph disease. Comparison with the unified multiple system atrophy rating scale. Mov Disord. 2007;22:1976–9.
Bürk K, Mälzig U, Wolf S, Heck S, Dimitriadis K, Schmitz-Hübsch T, et al. Comparison of three clinical rating scales in Friedreich ataxia (FRDA). Mov Disord. 2009;24:1779–84.
Fahey MC, Corben L, Collins V, Churchyard AJ, Delatycki MB. How is disease progress in Friedreich’s ataxia best measured? A study of four rating scales. J Neurol Neurosurg Psychiatry. 2007;78:411.
França Jr MC, D’Abreu A, Nucci A, Cendes F, Lopes-Cendes I. Progression of ataxia in patients with Machado–Joseph disease. Mov Disord. 2009;24:1387–90.
Di Prospero NA, Baker A, Jeffries N, Fischbeck KH. Neurological effects of high-dose idebenone in patients with Friedreich’s ataxia: a randomised, placebo-controlled trial. Lancet Neurol. 2007;6:878–86.
Lynch DR, Perlman SL, Meier T. A phase 3, double-blind, placebo-controlled trial of idebenone in Friedreich ataxia. Arch Neurol. 2010;67:941–7.
Ristori G, Romano S, Visconti A, Cannoni S, Spadaro M, Frontali M, et al. Riluzole in cerebellar ataxia: a randomized, double-blind, placebo-controlled pilot trial. Neurology. 2010;74:839–45.
Bier JC, Dethy S, Hildebrand J, Jacquy J, Manto M, Martin JJ, et al. Effects of the oral form of ondansetron on cerebellar dysfunction. A multi-center double-blind study. J Neurol. 2003;250:693–7.
Mori M, Adachi Y, Mori N, Kurihara S, Kashiwaya Y, Kusumi M, et al. Double-blind crossover study of branched-chain amino acid therapy in patients with spinocerebellar degeneration. J Neurol Sci. 2002;195:149–52.
Heo JH, Lee ST, Chu K, Kim M. The efficacy of combined estrogen and buspirone treatment in olivopontocerebellar atrophy. J Neurol Sci. 2008;271:87–90.
Assadi M, Campellone JV, Janson CG, Veloski JJ, Schwartzman RJ, Leone P. Treatment of spinocerebellar ataxia with buspirone. J Neurol Sci. 2007;260:143–6.
Cooper JM, Korlipara LV, Hart PE, Bradley JL, Schapira AH. Coenzyme Q10 and vitamin E deficiency in Friedreich’s ataxia: predictor of efficacy of vitamin E and coenzyme Q10 therapy. Eur J Neurol. 2008;15:1371–9.
Mariotti C, Solari A, Torta D, Marano L, Fiorentini C, Di Donato S. Idebenone treatment in Friedreich patients: 1-year-long randomized placebo-controlled trial. Neurology. 2003;60:1676–9.
Schöls L, Vorgerd M, Schillings M, Skipka G, Zange J. Idebenone in patients with Friedreich ataxia. Neurosci Lett. 2001;306:169–72.
Schmitz-Hübsch T, du Montcel ST, Baliko L, Berciano J, Boesch S, Depondt C, et al. Scale for the assessment and rating of ataxia: development of a new clinical scale. Neurology. 2006;66:1717–20.
Braga-Neto P, Godeiro-Junior C, Dutra LA, Pedroso JL, Barsottini OG. Translation and validation into Brazilian version of the Scale of the Assessment and Rating of Ataxia (SARA). Arq Neuropsiquiatr. 2010;68:228–30.
Weyer A, Abele M, Schmitz-Hübsch T, Schoch B, Frings M, Timmann D, et al. Reliability and validity of the scale for the assessment and rating of ataxia: a study in 64 ataxia patients. Mov Disord. 2007;22:1633–7.
Schmitz-Hübsch T, Fimmers R, Rakowicz M, Rola R, Zdzienicka E, Fancellu R, et al. Responsiveness of different rating instruments in spinocerebellar ataxia patients. Neurology. 2010;74:678–84.
Chan E, Charles P, Ribai P, Goizet C, Marelli C, Vincitorio CM, et al. Quantitative assessment of the evolution of cerebellar signs in spinocerebellar ataxias. Mov Disord. 2011;26:534–8. doi:10.1002/mds.23531.
Gazulla J, Benavente I. Single-blind, placebo-controlled pilot study of pregabalin for ataxia in cortical cerebellar atrophy. Acta Neurol Scand. 2007;116:235–8.
Schmahmann JD, Gardner R, MacMore J, Vangel MG. Development of a brief ataxia rating scale (BARS) based on a modified form of the ICARS. Mov Disord. 2009;24:1820–8.
Wenning GK, Tison F, Seppi K, Sampaio C, Diem A, Yekhlef F, et al. Multiple System Atrophy Study Group. Development and validation of the Unified Multiple System Atrophy Rating Scale (UMSARS). Mov Disord. 2004;19:1391–402.
Schwab R, England A. Projection technique for evaluating surgery in Parkinson’s disease. In: Gillingham F, Donaldson I, editors. Third symposium on Parkinson’s disease. Edinburgh: Livingstone; 1969. p. 152–75.
Geser F, Seppi K, Stampfer-Kountchev M, Köllensperger M, Diem A, Ndayisaba JP, et al. The European Multiple System Atrophy-Study Group (EMSA-SG). J Neural Transm. 2005;112:1677–86.
Geser F, Wenning GK, Seppi K, Stampfer-Kountchev M, Scherfler C, Sawires M, et al. Progression of multiple system atrophy (MSA): a prospective natural history study by the European MSA Study Group (EMSA SG). Mov Disord. 2006;21:179–86.
May S, Gilman S, Sowell BB, Thomas RG, Stern MB, Colcher A, et al. Potential outcome measures and trial design issues for multiple system atrophy. Mov Disord. 2007;22:2371–7.
Dodel R, Spottke A, Gerhard A, Reuss A, Reinecker S, Schimke N, et al. Minocycline 1-year therapy in multiple-system-atrophy: effect on clinical symptoms and [(11)C] (R)-PK11195 PET (MEMSA-trial). Mov Disord. 2010;25:97–107.
Holmberg B, Johansson JO, Poewe W, Wenning G, Quinn NP, Mathias C, et al. Safety and tolerability of growth hormone therapy in multiple system atrophy: a double-blind, placebo-controlled study. Mov Disord. 2007;22:1138–44.
Subramony SH, May W, Lynch D, Gomez C, Fischbeck K, Hallett M, et al. Measuring Friedreich ataxia: interrater reliability of a neurologic rating scale. Neurology. 2005;64:1261–2.
Lynch DR, Farmer JM, Tsou AY, Perlman S, Subramony SH, Gomez CM, et al. Measuring Friedreich ataxia: complementary features of examination and performance measures. Neurology. 2006;66:1711–6.
Friedman LS, Farmer JM, Perlman S, Wilmot G, Gomez CM, Bushara KO, et al. Measuring the rate of progression in Friedreich ataxia: implications for clinical trial design. Mov Disord. 2010;25(4):426–32.
Kieling C, Rieder CR, Silva AC, Saute JA, Cecchin CR, Monte TL, et al. A neurological examination score for the assessment of spinocerebellar ataxia 3 (SCA3). Eur J Neurol. 2008;15:371–6.
Jardim LB, Hauser L, Kieling C, Saute JA, Xavier R, Rieder CR, et al. Progression rate of neurological deficits in a 10-year cohort of SCA3 patients. Cerebellum. 2010;9:419–28.
Schmitz-Hübsch T, Coudert M, Bauer P, Giunti P, Globas C, Baliko L, et al. Spinocerebellar ataxia types 1, 2, 3, and 6: disease severity and nonataxia symptoms. Neurology. 2008;71:982–9.
Després C, Lamoureux D, Beuter A. Standardization of a neuromotor test battery: the CATSYS system. Neurotoxicology. 2000;21(5):725–35.
Aguilar D, Sigford KE, Soontarapornchai K, Nguyen DV, Adams PE, Yuhas JM, et al. A quantitative assessment of tremor and ataxia in FMR1 premutation carriers using CATSYS. Am J Med Genet A. 2008;146A(5):629–35.
Allen EG, Juncos J, Letz R, Rusin M, Hamilton D, Novak G, et al. Detection of early FXTAS motor symptoms using the CATSYS computerised neuromotor test battery. J Med Genet. 2008;45(5):290–7.
Juncos JL, Lazarus JT, Graves-Allen E, Shubeck L, Rusin M, Novak G, et al. New clinical findings in the fragile X-associated tremor ataxia syndrome (FXTAS). Neurogenetics. 2011;12(2):123–35.
Assadi M, Leone P, Veloski JJ, Schwartzman RJ, Janson CG, Campellone JV. Validating an Ataxia Functional Composite Scale in spinocerebellar ataxia. J Neurol Sci. 2008;268(1–2):136–9.
du Montcel ST, Charles P, Ribai P, Goizet C, Le Bayon A, Labauge P, et al. Composite cerebellar functional severity score: validation of a quantitative score of cerebellar impairment. Brain. 2008;131:1352–61.
Schmitz-Hübsch T, Giunti P, Stephenson DA, Globas C, Baliko L, Saccà F, et al. SCA Functional Index: a useful compound performance measure for spinocerebellar ataxia. Neurology. 2008;71:486–92.
Cano SJ, Riazi A, Schapira AH, Cooper JM, Hobart JC. Friedreich’s ataxia impact scale: a new measure striving to provide the flexibility required by today’s studies. Mov Disord. 2009;24:984–92.
Streiner DL, Norman GR. Health measurement scales: a practical guide to their development and use. Oxford: Oxford University Press; 2008.
Molnar FJ, Man-Son-Hing M, Fergusson D. Systematic review of measures of clinical significance employed in randomized controlled trials of drugs for dementia. J Am Geriatr Soc. 2009;57(3):536–46.
Pulst SM. Ataxia rating scales in the balance. Nat Clin Pract Neurol. 2007;3:119.
Acknowledgments
We are grateful to the Latin-American Science and Technology Development Programme (CYTED) (210RT0390) for funding the RIBERMOV network, through which initiative this work took form. We thank the reviewers who provided important hints and fruitful suggestions that have considerably improved this review. L.B. Jardim was supported by CNPq, Brazil, and by INAGEMP, Brazil.
Conflict of Interest
All authors declare no conflicts of interest.
Author information
Authors and Affiliations
Consortia
Corresponding author
Rights and permissions
About this article
Cite this article
Saute, J.A.M., Donis, K.C., Serrano-Munuera, C. et al. Ataxia Rating Scales—Psychometric Profiles, Natural History and Their Application in Clinical Trials. Cerebellum 11, 488–504 (2012). https://doi.org/10.1007/s12311-011-0316-8
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12311-011-0316-8