285923 20260408170129.0 10.1093/brain/awaf408 doi pmid:41150672 pmid pmc:PMC12998449 pmc 0006-8950 ISSN 1460-2156 ISSN DZNE-2026-00369 English 610 Petit, Emilien 0009-0000-0602-7122 0 Predictive models for ataxia progression and conversion in spinocerebellar ataxia type 1 and 3. Oxford 2026 Oxford Univ. Press article DRIVER Output Types/Journal article DataCite Journal Article journal journal PUB:(DE-HGF)16 1775660392_30392 PUB:(DE-HGF) ARTICLE BibTeX JOURNAL_ARTICLE ORCID Journal Article 0 EndNote The READISCA study aims to prepare for clinical trials in spinocerebellar ataxia types 1 and 3 (SCA1 and SCA3). Hence, we searched for predictive variables of ataxia onset (phenoconversion) and progression. Individuals with SCA1 or SCA3 and controls were enrolled from 2018 to 2021 in the USA and Europe. Clinical scores, MRI measures and neurofilament light chain (NfL) levels were assessed annually for 5 years. In the pre-ataxic group at baseline, we compared phenoconverters with non-converters. A Bayesian mixed model was used to model the longitudinal progression of clinical scores and NfL levels. The impact of data-driven selected baseline variables (demographic, clinical and MRI) on the expected Scale for Assessment and Rating of Ataxia progression was tested. Forty-three controls, 55 SCA1 carriers and 124 SCA3 carriers were included; a subset of the cohort (n = 109) had MRI data. Converters from pre-ataxic to ataxic stages represented 5/22 (22%) and 12/38 (32%) for SCA1 and SCA3, respectively. Converters were more depressed (Patient Health Questionnaire 9: 3.9 ± 2.9 versus 2.3 ± 2.6, P = 0.04), had higher plasma NfL levels (17.6 ± 5.7 versus 11.1 ± 5.9 pg/ml, P < 0.0001), more cerebellar white matter atrophy (1.44% ± 0.12% of total intracranial volume versus 1.54% ± 0.16%, P = 0.032) and more Inventory of Non-Ataxia Signs signs (1.8 ± 1.3 versus 0.7 ± 0.8, P = 0.002). All clinical scores except Cerebellar Cognitive Affective Syndrome significantly worsened during the study. NfL levels significantly increased in non-converters and ataxic SCA3 (1.06 ± 0.33 pg/ml/year, P = 0.002 and 0.57 ± 0.21 pg/ml/year, P = 0.01, respectively) but not in controls and ataxic SCA1 (0.31 ± 0.26 pg/ml/year, P = 0.24 and 0.26 ± 0.42 pg/ml/year, P = 0.55, respectively). In the best predictive model of Scale for Assessment and Rating of Ataxia progression after 1 year (R2 = 0.54), factors linked with faster progression were higher functional stage (P < 0.001), higher Composite Cerebellar Functional Score (P = 0.002) and higher total creatine in cerebellar white matter (P = 0.026). Factors significantly linked to conversion, namely NfL levels, depression and lower motor neuron involvement, differ from those driving disease progression. The NfL levels and lower motor neuron signs could be used as predictors of phenoconversion and MRI variables as ataxia progression predictors. Psychological care should be provided in the pre-ataxic phase of the disease. 353 - Clinical and Health Care Research (POF4-353) G:(DE-HGF)POF4-353 POF4-353 POF IV 0 Dataset connected to CrossRef, PubMed, , Journals: pub.dzne.de biomarkers Other brain MRI Other clinical scales Other natural history study Other spinocerebellar ataxia Other Neurofilament Proteins NLM Chemicals neurofilament protein L NLM Chemicals Humans MeSH Male MeSH Disease Progression MeSH Female MeSH Middle Aged MeSH Adult MeSH Magnetic Resonance Imaging MeSH Machado-Joseph Disease: diagnostic imaging MeSH Spinocerebellar Ataxias: diagnostic imaging MeSH Neurofilament Proteins: blood MeSH Longitudinal Studies MeSH Aged MeSH Coarelli, Giulia 1 Morgan, David 2 Cunha, Paulina 3 Hurmic, Hortense 4 Faber, Jennifer P:(DE-2719)2811327 5 Grobe-Einsler, Marcus P:(DE-2719)9001510 6 dzne Rezende, Thiago 7 Kuo, Sheng-Han 8 Wilmot, George R 9 Rosenthal, Liana S 10 Schmahmann, Jeremy D 11 Yacoubian, Talene A 12 Perlman, Susan L 13 Geschwind, Michael D 0000-0003-2861-3776 14 Gomez, Christopher M 15 Hawkins, Trevor 16 Subramony, S. H. 17 Shakkottai, Vikram G 18 Bushara, Khalaf O 19 Zesiewicz, Theresa A 20 Pulst, Stefan M 21 Park, Young Woo P:(DE-HGF)0 22 Lenglet, Christophe 23 Klockgether, Thomas P:(DE-2719)2810314 24 dzne Paulson, Henry L 25 Durr, Alexandra P:(DE-2719)9000429 26 Öz, Gülin 27 Ashizawa, Tetsuo 28 Tezenas du Montcel, Sophie 0000-0002-2866-4330 29 10.1093/brain/awaf408 Vol. 149, no. 4, p. 1268 - 1277 PERI:(DE-600)1474117-9 4 1268 - 1277 Brain 149 2026 0006-8950 http://pub.dzne.de/record/285923/files/DZNE-2026-00369_Restricted.pdf http://pub.dzne.de/record/285923/files/DZNE-2026-00369_Restricted.pdf?subformat=pdfa pdfa Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 5 P:(DE-2719)2811327 External Institute I:(DE-HGF)0 Extern 6 P:(DE-2719)9001510 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 24 P:(DE-2719)2810314 DE-HGF Gesundheit Neurodegenerative Diseases G:(DE-HGF)POF4-350 G:(DE-HGF)POF4-353 G:(DE-HGF)POF4 G:(DE-HGF)POF4-300 G:(DE-HGF)POF Clinical and Health Care Research 0 2026 Nationallizenz StatID:(DE-HGF)0420 StatID 2024-12-12 ger JCR StatID:(DE-HGF)0100 StatID BRAIN : 2022 2024-12-12 DBCoverage StatID:(DE-HGF)0200 StatID SCOPUS 2024-12-12 DBCoverage StatID:(DE-HGF)0300 StatID Medline 2024-12-12 DBCoverage StatID:(DE-HGF)0600 StatID Ebsco Academic Search 2024-12-12 Peer Review StatID:(DE-HGF)0030 StatID ASC 2024-12-12 DBCoverage StatID:(DE-HGF)0199 StatID Clarivate Analytics Master Journal List 2024-12-12 DBCoverage StatID:(DE-HGF)1050 StatID BIOSIS Previews 2024-12-12 DBCoverage StatID:(DE-HGF)0160 StatID Essential Science Indicators 2024-12-12 DBCoverage StatID:(DE-HGF)1030 StatID Current Contents - Life Sciences 2024-12-12 DBCoverage StatID:(DE-HGF)1190 StatID Biological Abstracts 2024-12-12 DBCoverage StatID:(DE-HGF)1110 StatID Current Contents - Clinical Medicine 2024-12-12 WoS StatID:(DE-HGF)0113 StatID Science Citation Index Expanded 2024-12-12 DBCoverage StatID:(DE-HGF)0150 StatID Web of Science Core Collection 2024-12-12 IF >= 10 StatID:(DE-HGF)9910 StatID BRAIN : 2022 2024-12-12 I:(DE-2719)1011001 Clinical Research (Bonn) Clinical Research Coordination 0 I:(DE-2719)1011101 Patient Studies (Bonn) Patient Studies (Bonn) 1 journal EDITORS VDBINPRINT I:(DE-2719)1011001 I:(DE-2719)1011101 UNRESTRICTED