Authors

Jennifer Faber, Deutsches Zentrum für Neurodegenerative Erkrankungen e.V.
Tamara Schaprian, Deutsches Zentrum für Neurodegenerative Erkrankungen e.V.
Koyak Berkan, Deutsches Zentrum für Neurodegenerative Erkrankungen e.V.
Kathrin Reetz, Rheinisch-Westfälische Technische Hochschule Aachen
Marcondes Cavalcante França, Brazilian Institute of Neuroscience and Neurotechnology (BRAINN)
Thiago Junqueira Ribeiro de Rezende, Brazilian Institute of Neuroscience and Neurotechnology (BRAINN)
Jiang Hong, Central South University
Weihua Liao, Central South University
Bart van de Warrenburg, Radboud University Medical Center
Judith van Gaalen, Radboud University Medical Center
Alexandra Durr, Sorbonne Universite
Fanny Mochel, Sorbonne Universite
Paola Giunti, UCL Queen Square Institute of Neurology
Hector Garcia-Moreno, UCL Queen Square Institute of Neurology
Ludger Schoels, Hertie-Institut für klinische Hirnforschung
Holger Hengel, Hertie-Institut für klinische Hirnforschung
Matthis Synofzik, Hertie-Institut für klinische Hirnforschung
Benjamin Bender, Universitätsklinikum und Medizinische Fakultät Tübingen
Gulin Oz, University of Minnesota Medical School
James Joers, University of Minnesota Medical School
Jereon J. de Vries, Universitair Medisch Centrum Groningen
Jun Suk Kang, Goethe-Universität Frankfurt am Main
Dagmar Timmann-Braun, Universitätsklinikum Essen
Heike Jacobi, Universitätsklinikum Heidelberg
Jon Infante, Hospital Universitario Marqués de Valdecilla
Richard Joules, IXICO plc
Sandro Romanzetti, Forschungszentrum Jülich (FZJ)
Jorn Diedrichsen, Western UniversityFollow
Matthias Schmid, Deutsches Zentrum für Neurodegenerative Erkrankungen e.V.
Robin Wolz, IXICO plc
Thomas Klockgether, Deutsches Zentrum für Neurodegenerative Erkrankungen e.V.

Document Type

Article

Publication Date

10-1-2021

Journal

Movement Disorders

Volume

36

Issue

10

First Page

2273

Last Page

2281

URL with Digital Object Identifier

10.1002/mds.28610

Abstract

Background: Given that new therapeutic options for spinocerebellar ataxias are on the horizon, there is a need for markers that reflect disease-related alterations, in particular, in the preataxic stage, in which clinical scales are lacking sensitivity. Objective: The objective of this study was to quantify regional brain volumes and upper cervical spinal cord areas in spinocerebellar ataxia type 3 in vivo across the entire time course of the disease. Methods: We applied a brain segmentation approach that included a lobular subsegmentation of the cerebellum to magnetic resonance images of 210 ataxic and 48 preataxic spinocerebellar ataxia type 3 mutation carriers and 63 healthy controls. In addition, cervical cord cross-sectional areas were determined at 2 levels. Results: The metrics of cervical spinal cord segments C3 and C2, medulla oblongata, pons, and pallidum, and the cerebellar anterior lobe were reduced in preataxic mutation carriers compared with controls. Those of cervical spinal cord segments C2 and C3, medulla oblongata, pons, midbrain, cerebellar lobules crus II and X, cerebellar white matter, and pallidum were reduced in ataxic compared with nonataxic carriers. Of all metrics studied, pontine volume showed the steepest decline across the disease course. It covaried with ataxia severity, CAG repeat length, and age. The multivariate model derived from this analysis explained 46.33% of the variance of pontine volume. Conclusion: Regional brain and spinal cord tissue loss in spinocerebellar ataxia type 3 starts before ataxia onset. Pontine volume appears to be the most promising imaging biomarker candidate for interventional trials that aim at slowing the progression of spinocerebellar ataxia type 3. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Creative Commons License

Creative Commons Attribution-Noncommercial 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial 4.0 License

Citation of this paper:

Faber, J., Schaprian, T., Berkan, K., Reetz, K., França, M.C., Jr, de Rezende, T.J.R., Hong, J., Liao, W., van de Warrenburg, B., van Gaalen, J., Durr, A., Mochel, F., Giunti, P., Garcia-Moreno, H., Schoels, L., Hengel, H., Synofzik, M., Bender, B., Oz, G., Joers, J., de Vries, J.J., Kang, J.-S., Timmann-Braun, D., Jacobi, H., Infante, J., Joules, R., Romanzetti, S., Diedrichsen, J., Schmid, M., Wolz, R. and Klockgether, T. (2021), Regional Brain and Spinal Cord Volume Loss in Spinocerebellar Ataxia Type 3. Mov Disord, 36: 2273-2281. https://doi.org/10.1002/mds.28610

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