期刊
MOVEMENT DISORDERS
卷 36, 期 4, 页码 985-994出版社
WILEY
DOI: 10.1002/mds.28466
关键词
spinocerebellar ataxia type 3; biomarkers; pre-ataxic period
资金
- Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES) [99999.008137/2015-03]
- Fundacao do Amparo a Pesquisa do Rio Grande do Sul (FAPERGS) [17/2551-0001 035-3, 17/2551-0001 1463-4]
- Fundo de Incentivo a Pesquisa do Hospital de Clinicas de Porto Alegre (FIPEHCPA) [17-0014, 17-0015, 17-0201]
- CAPES
- FAPERGS
- Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq), Brazil
This study validates biomarkers for disease progression in spinocerebellar ataxia type 3 patients before symptoms appear. Clinical scales and oculomotor neurophysiology variables were already altered in pre-ataxic patients and worsened with time, making them good candidates to measure preclinical changes.
Background: The pathological burden of spinocerebellar ataxia type 3, also known as Machado-Joseph disease (SCA3/MJD), accumulates before the beginning of symptoms. Our study aims at validating biomarkers for disease progression since pre-ataxic periods. We report on baseline findings of clinical scales and oculomotor neurophysiology. Methods: Ataxic (Scale for the Assessment and Rating of Ataxia > 2.5) and at 50% risk subjects were included. The latter were subdivided into noncarriers, pre-ataxic carriers near (PAN), or pre-ataxic carriers far from (PAFF) ataxia onset (AO), with 4 years from the predicted age at onset being the cutoff. The subjects were assessed by Neurological Examination Score for Spinocerebellar Ataxia (NESSCA), International Cooperative Ataxia Rating Scale (ICARS), Inventory of Non-Ataxic Signs (INAScount), Composite Cerebellar Functions Score and SCA Functional Index, and video-oculography, including the regression slope of vestibulo-ocular reflex gain (VORr), main sequence of volitional and reflexive vertical saccades, slow-phase velocity of central and gaze-evoked (SPV-GE) nystagmus, and vertical pursuit gain. Correction for multiple comparisons was performed; the threshold for statistical significance was P < 0.05. Results: A total of 35 ataxic, 14 PAN, 24 PAFF, and 22 noncarriers were included. All variables showed significant differences between groups and correlated to time to onset or time after onset, among all 73 SCA3/MJD carriers; none significantly changed with age in controls. NESSCA, ICARS, INAScount, VORr, main sequence of volitional saccades, and SPV-GE not only distinguished PAN from controls but also correlated with time left to AO. Conclusions: Clinical scales and video-oculography variables were already altered in pre-ataxic SCA3/MJD carriers and worsened with time. NESSCA, ICARS, INAScount, VORr, main sequence of vertical volitional saccades, and SPV-GE are good candidates to measure preclinical changes in SCA3/MJD. (c) 2021 International Parkinson and Movement Disorder Society
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