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@ARTICLE{Petit:285923,
      author       = {Petit, Emilien and Coarelli, Giulia and Morgan, David and
                      Cunha, Paulina and Hurmic, Hortense and Faber, Jennifer and
                      Grobe-Einsler, Marcus and Rezende, Thiago and Kuo, Sheng-Han
                      and Wilmot, George R and Rosenthal, Liana S and Schmahmann,
                      Jeremy D and Yacoubian, Talene A and Perlman, Susan L and
                      Geschwind, Michael D and Gomez, Christopher M and Hawkins,
                      Trevor and Subramony, S. H. and Shakkottai, Vikram G and
                      Bushara, Khalaf O and Zesiewicz, Theresa A and Pulst, Stefan
                      M and Park, Young Woo and Lenglet, Christophe and
                      Klockgether, Thomas and Paulson, Henry L and Durr, Alexandra
                      and Öz, Gülin and Ashizawa, Tetsuo and Tezenas du Montcel,
                      Sophie},
      title        = {{P}redictive models for ataxia progression and conversion
                      in spinocerebellar ataxia type 1 and 3.},
      journal      = {Brain},
      volume       = {149},
      number       = {4},
      issn         = {0006-8950},
      address      = {Oxford},
      publisher    = {Oxford Univ. Press},
      reportid     = {DZNE-2026-00369},
      pages        = {1268 - 1277},
      year         = {2026},
      abstract     = {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.},
      keywords     = {Humans / Male / Disease Progression / Female / Middle Aged
                      / Adult / Magnetic Resonance Imaging / Machado-Joseph
                      Disease: diagnostic imaging / Spinocerebellar Ataxias:
                      diagnostic imaging / Neurofilament Proteins: blood /
                      Longitudinal Studies / Aged / biomarkers (Other) / brain MRI
                      (Other) / clinical scales (Other) / natural history study
                      (Other) / spinocerebellar ataxia (Other) / Neurofilament
                      Proteins (NLM Chemicals) / neurofilament protein L (NLM
                      Chemicals)},
      cin          = {Clinical Research (Bonn) / Patient Studies (Bonn)},
      ddc          = {610},
      cid          = {I:(DE-2719)1011001 / I:(DE-2719)1011101},
      pnm          = {353 - Clinical and Health Care Research (POF4-353)},
      pid          = {G:(DE-HGF)POF4-353},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:41150672},
      pmc          = {pmc:PMC12998449},
      doi          = {10.1093/brain/awaf408},
      url          = {https://pub.dzne.de/record/285923},
}