Journal Article

DZNE-2026-00913

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png A Severity-Agnostic Atrophy Pattern in Spinocerebellar Ataxia Type 3: Volumetrics from ENIGMA-Ataxia.

Robertson, J. W. ; Adanyeguh, I. ; Arpin, D. J. ; Ashizawa, T. ; Bender, B. ; Cendes, F. ; Chen, X. ; Coarelli, G. ; Coutinho, L. ; Deistung, A. ; Dogan, I. ; Durr, A. ; Faber, J.DZNE* ; Group, E. M. S. (Collaboration Author) ; Fernandez-Ruiz, J. ; Ferreira, M.DZNE* ; França, M. C. ; Göricke, S. L. ; Han, S. ; Klockgether, T.DZNE* ; Liu, C. ; Luo, J. ; Martinez, A. R. M. ; Ono, S. E. ; Onyike, C. U. ; Öz, G. ; Group, E. M. S. (Collaboration Author) ; Paulson, H. ; Prince, J. L. ; Reetz, K. ; Rezende, T. J. R. ; Synofzik, M.DZNE* ; Ghizoni Teive, H. A. ; Thomopoulos, S. I. ; Thompson, P. M. ; Timmann, D. ; Vaillancourt, D. ; van de Warrenburg, B. ; van Gaalen, J. ; Wang, X. ; Wegner, P.DZNE* ; Ying, S. H. ; Harding, I. H. ; Hernandez-Castillo, C. R.

2026
Wiley New York, NY

This record in other databases:    

Please use a persistent id in citations: doi:10.1002/mds.70349

Abstract: Spinocerebellar ataxia type 3 (SCA3) is a rare, inherited neurodegenerative disease characterized by progressive loss of motor coordination.We undertook a multisite magnetic resonance imaging study to profile the spatial spread of atrophy across the brain, determine whether atrophy preferentially maps onto specific functional networks, and investigate the relationship between cerebellar and cerebral atrophy.Whole-brain grey and white matter (GM and WM) voxel-based morphometry was performed on 408 individuals with SCA3 (82 pre-ataxic) and 293 controls. The SCA3 cohort was stratified by ataxia severity to study progression. Cerebellar GM atrophy was mapped onto a task-based functional atlas. Cerebrocerebellar volumetric covariance was assessed to determine whether cerebral and cerebellar atrophy were coupled.The atrophy pattern is spatially consistent but progressive in magnitude across the disease course. The greatest atrophy (Cohen's d > 1.5) occurred in the pons, cerebellar WM, and cerebellar peduncles; correlations with ataxia severity and duration were also strongest (-0.4 > r > -0.65) in those regions. Cerebellar GM atrophy was greatest (d ≅ 0.7) in functional regions associated with motor planning/execution, attention, and emotional processing. Sparse cerebral cortical atrophy appears only in the most severe disease subgroup, while striatal atrophy begins in the earliest stages but does not worsen with increasing clinical severity. Reduced cerebrocerebellar volumetric covariance is observed in SCA3 participants versus controls.Cerebellar and brainstem atrophy underlies greater ataxia severity in SCA3, but the spatial pattern of structural changes remains relatively consistent across the course of the disease. Cerebellar GM atrophy is spatially non-uniform, and occurs maximally in regions consistent with the motor and cognitive clinical presentation of SCA3. Cerebellar atrophy is not mirrored by corresponding cerebral structural changes. © 2026 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Keyword(s): Humans (MeSH) ; Female (MeSH) ; Male (MeSH) ; Atrophy: pathology (MeSH) ; Magnetic Resonance Imaging (MeSH) ; Machado-Joseph Disease: pathology (MeSH) ; Machado-Joseph Disease: diagnostic imaging (MeSH) ; Middle Aged (MeSH) ; Gray Matter: pathology (MeSH) ; Gray Matter: diagnostic imaging (MeSH) ; Adult (MeSH) ; Severity of Illness Index (MeSH) ; White Matter: pathology (MeSH) ; White Matter: diagnostic imaging (MeSH) ; Cerebellum: pathology (MeSH) ; Cerebellum: diagnostic imaging (MeSH) ; Aged (MeSH) ; Brain: pathology (MeSH) ; Brain: diagnostic imaging (MeSH) ; Disease Progression (MeSH) ; Cerebrocerebellar connectivity ; Functional brain networks ; Neurodegeneration ; Spinocerebellar Ataxia ; Voxel‐based morphometry

---

Contributing Institute(s):

1. Clinical Research Coordination (Clinical Research (Bonn))
2. Clinical Neuroimaging (AG Radbruch)
3. Patient Studies (Bonn) (Patient Studies (Bonn))
4. Parkinson Genetics (AG Gasser)
5. Clinical Research Platform (CRP) (Clinical Research Platform (CRP))

Research Program(s):

1. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)

Appears in the scientific report 2026

---

Database coverage:
; ; ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; DEAL Wiley ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 5 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

---