Differential Temporal Dynamics of Axial and Appendicular Ataxia in SCA3.
Scale for the Assessment and Rating of Ataxia
disease progression
natural history
spinocerebellar ataxia type 3
Journal
Movement disorders : official journal of the Movement Disorder Society
ISSN: 1531-8257
Titre abrégé: Mov Disord
Pays: United States
ID NLM: 8610688
Informations de publication
Date de publication:
09 2022
09 2022
Historique:
revised:
20
05
2022
received:
10
02
2022
accepted:
06
06
2022
pubmed:
10
7
2022
medline:
16
9
2022
entrez:
9
7
2022
Statut:
ppublish
Résumé
Disease severity in spinocerebellar ataxia type 3 (SCA3) is commonly defined by the Scale for the Assessment and Rating of Ataxia (SARA) sum score, but little is known about the contributions and progression patterns of individual items. To investigate the temporal dynamics of SARA item scores in SCA3 patients and evaluate if clinical and demographic factors are differentially associated with evolution of axial and appendicular ataxia. In a prospective, multinational cohort study involving 11 European and 2 US sites, SARA scores were determined longitudinally in 223 SCA3 patients with a follow-up assessment after 1 year. An increase in SARA score from 10 to 20 points was mainly driven by axial and speech items, with a markedly smaller contribution of appendicular items. Finger chase and nose-finger test scores not only showed the lowest variability at baseline, but also the least deterioration at follow-up. Compared with the full set of SARA items, omission of both tests would result in lower sample size requirements for therapeutic trials. Sex was associated with change in SARA sum score and appendicular, but not axial, subscore, with a significantly faster progression in men. Despite considerable interindividual variability, the average annual progression rate of SARA score was approximately three times higher in subjects with a disease duration over 10 years than in those within 10 years from onset. Our findings provide evidence for a difference in temporal dynamics between axial and appendicular ataxia in SCA3 patients, which will help inform the design of clinical trials and development of new (etiology-specific) outcome measures. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Sections du résumé
BACKGROUND
Disease severity in spinocerebellar ataxia type 3 (SCA3) is commonly defined by the Scale for the Assessment and Rating of Ataxia (SARA) sum score, but little is known about the contributions and progression patterns of individual items.
OBJECTIVES
To investigate the temporal dynamics of SARA item scores in SCA3 patients and evaluate if clinical and demographic factors are differentially associated with evolution of axial and appendicular ataxia.
METHODS
In a prospective, multinational cohort study involving 11 European and 2 US sites, SARA scores were determined longitudinally in 223 SCA3 patients with a follow-up assessment after 1 year.
RESULTS
An increase in SARA score from 10 to 20 points was mainly driven by axial and speech items, with a markedly smaller contribution of appendicular items. Finger chase and nose-finger test scores not only showed the lowest variability at baseline, but also the least deterioration at follow-up. Compared with the full set of SARA items, omission of both tests would result in lower sample size requirements for therapeutic trials. Sex was associated with change in SARA sum score and appendicular, but not axial, subscore, with a significantly faster progression in men. Despite considerable interindividual variability, the average annual progression rate of SARA score was approximately three times higher in subjects with a disease duration over 10 years than in those within 10 years from onset.
CONCLUSION
Our findings provide evidence for a difference in temporal dynamics between axial and appendicular ataxia in SCA3 patients, which will help inform the design of clinical trials and development of new (etiology-specific) outcome measures. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Identifiants
pubmed: 35808813
doi: 10.1002/mds.29135
pmc: PMC9540189
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1850-1860Subventions
Organisme : Medical Research Council
Pays : United Kingdom
Informations de copyright
© 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Références
Orphanet J Rare Dis. 2013 Nov 13;8:177
pubmed: 24225362
Neurology. 2006 Jun 13;66(11):1717-20
pubmed: 16769946
Neurol Genet. 2020 Mar 20;6(3):e415
pubmed: 32337342
Nat Rev Dis Primers. 2019 Apr 11;5(1):24
pubmed: 30975995
Neurology. 2010 Feb 23;74(8):678-84
pubmed: 20177122
Brain. 1998 Apr;121 ( Pt 4):589-600
pubmed: 9577387
Mov Disord. 2021 Oct;36(10):2367-2377
pubmed: 34115419
Cerebellum. 2013 Jun;12(3):418-28
pubmed: 23090211
Curr Opin Neurol. 2008 Apr;21(2):111-6
pubmed: 18317266
Brain Stimul. 2021 Mar-Apr;14(2):351-357
pubmed: 33535082
Adv Exp Med Biol. 2018;1049:233-241
pubmed: 29427106
Lancet Neurol. 2015 Oct;14(10):985-91
pubmed: 26321318
Neurology. 2011 Sep 13;77(11):1035-41
pubmed: 21832228
Orphanet J Rare Dis. 2018 Jan 25;13(1):20
pubmed: 29370806
Neuroepidemiology. 2014;42(3):174-83
pubmed: 24603320
Neurology. 2008 Aug 12;71(7):486-92
pubmed: 18695159
Front Hum Neurosci. 2017 Dec 13;11:605
pubmed: 29326569
Clin Genet. 2007 Dec;72(6):543-5
pubmed: 17894834
Neurology. 2015 Jul 7;85(1):96-103
pubmed: 26062625
Mov Disord. 2021 Oct;36(10):2273-2281
pubmed: 33951232
Neurotherapeutics. 2022 May 2;:
pubmed: 35501469
Lancet Neurol. 2015 Nov;14(11):1101-8
pubmed: 26377379
Hum Mutat. 2012 Sep;33(9):1324-32
pubmed: 22689585
Lancet Neurol. 2013 Jul;12(7):650-8
pubmed: 23707147
Cerebellum. 2014 Apr;13(2):237-42
pubmed: 24197754
Ann Neurol. 2018 Sep;84(3):401-408
pubmed: 30014526
Arch Neurol. 2012 Apr;69(4):500-8
pubmed: 22491195
Mov Disord. 2014 Apr;29(4):568-73
pubmed: 24399647
Parkinsonism Relat Disord. 2021 Oct;91:37-41
pubmed: 34479057
Mov Disord. 2021 Feb;36(2):283-297
pubmed: 33022077