Evidence map›Paper›PMID 42108727›Full record

ArticleMovement disorders : official journal of the Movement Disorder Society2026

A Severity-Agnostic Atrophy Pattern in Spinocerebellar Ataxia Type 3: Volumetrics from ENIGMA-Ataxia.

Jason W Robertson, Isaac Adanyeguh, David J Arpin, Tetsuo Ashizawa, Benjamin Bender, Fernando Cendes, Xi Chen, Giulia Coarelli, Léo Coutinho, Andreas Deistung and 34 more

Abstract readMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Movement disorders : official journal of the Movement Disorder Society, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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1 · What the graph read from it

What it found

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

44 authors.

Jason W RobertsonFaculty of Computer Science, Dalhousie University, Halifax, Nova Scotia, Canada.ORCID https://orcid.org/0000-0003-0579-0403
Isaac AdanyeguhDepartment of Radiology, Center for Magnetic Resonance Research, University of Minnesota Medical School, Minneapolis, Minnesota, USA.ORCID https://orcid.org/0000-0003-1402-5877
David J ArpinDepartment of Applied Physiology & Kinesiology, University of Florida, Gainesville, Florida, USA.ORCID https://orcid.org/0000-0002-6442-1205
Tetsuo AshizawaDepartment of Neurology, Weill Cornell Medicine at Houston Methodist Research Institute, Houston, Texas, USA.
Benjamin BenderDepartment of Diagnostic and Interventional Neuroradiology, University Hospital Tübingen, Tübingen, Germany.ORCID https://orcid.org/0000-0002-3205-4631
Fernando CendesDepartment of Neurology, School of Medical Sciences, University of Campinas, Campinas, Brazil.ORCID https://orcid.org/0000-0001-9336-9568
Xi Chen7T Magnetic Resonance Imaging Translational Medical Center, Department of Radiology, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, China.
Giulia CoarelliSorbonne Université, Paris Brain Institute (ICM), Pitié-Salpêtrière Hospital, AP-HP, INSERM, CNRS, University Hospital Pitié-Salpêtrière, Paris, France.
Léo CoutinhoPost-Graduate Program of Internal Medicine, Internal Medicine Department, Hospital de Clínicas, Federal University of Paraná, Curitiba, Brazil.
Andreas DeistungDepartment for Radiation Medicine, University Clinic and Outpatient Clinic for Radiology, University Hospital Halle (Saale), University Medicine Halle, Halle (Saale), Germany.ORCID https://orcid.org/0000-0002-2427-1302
Imis DoganDepartment of Neurology, RWTH Aachen University, Aachen, Germany.
Alexandra DurrSorbonne Université, Paris Brain Institute (ICM), Pitié-Salpêtrière Hospital, AP-HP, INSERM, CNRS, University Hospital Pitié-Salpêtrière, Paris, France.ORCID https://orcid.org/0000-0002-8921-7104
Jennifer FaberGerman Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
ESMI MR Study Group
Juan Fernandez-RuizNeuropsychology Laboratory, Department of Physiology, Faculty of Medicine, National Autonomous University of Mexico, Mexico City, Mexico.
Mónica FerreiraGerman Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
Marcondes C FrançaDepartment of Neurology, School of Medical Sciences, University of Campinas, Campinas, Brazil.
Sophia L GörickeCenter for Translational Neuro- and Behavioral Sciences (C-TNBS), Essen University Hospital, University of Duisburg-Essen, Essen, Germany.
Shuo HanDepartment of Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland, USA.
Thomas KlockgetherGerman Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.ORCID https://orcid.org/0000-0001-6174-5442
Chen Liu7T Magnetic Resonance Imaging Translational Medical Center, Department of Radiology, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, China.ORCID https://orcid.org/0000-0001-5149-2496
Jun Luo7T Magnetic Resonance Imaging Translational Medical Center, Department of Radiology, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, China.
Alberto R M MartinezDepartment of Neurology, School of Medical Sciences, University of Campinas, Campinas, Brazil.ORCID https://orcid.org/0000-0001-7160-0853
Sergio E OnoClínica DAPI-Diagnóstico Avançado Por Imagem, Curitiba, Brazil.
Chiadi U OnyikeDepartment of Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, Maryland, USA.
Gülin ÖzDepartment of Radiology, Center for Magnetic Resonance Research, University of Minnesota Medical School, Minneapolis, Minnesota, USA.
EUROSCA MR Study Group
Henry PaulsonDepartment of Neurology, University of Michigan, Ann Arbor, Michigan, USA.
Jerry L PrinceDepartment of Electrical and Computer Engineering, Johns Hopkins University, Baltimore, Maryland, USA.ORCID https://orcid.org/0000-0002-6553-0876
Kathrin ReetzDepartment of Neurology, RWTH Aachen University, Aachen, Germany.ORCID https://orcid.org/0000-0002-9730-9228
Thiago J R RezendeDepartment of Neurology, School of Medical Sciences, University of Campinas, Campinas, Brazil.ORCID https://orcid.org/0000-0001-8453-0313
Matthis SynofzikDepartment of Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, Tübingen, Germany.
Hélio A Ghizoni TeivePost-Graduate Program of Internal Medicine, Internal Medicine Department, Hospital de Clínicas, Federal University of Paraná, Curitiba, Brazil.
Sophia I ThomopoulosImaging Genetics Center, Mark and Mary Stevens Institute for Neuroimaging and Informatics, Keck School of Medicine, University of Southern California, Marina del Rey, California, USA.
Paul M ThompsonImaging Genetics Center, Mark and Mary Stevens Institute for Neuroimaging and Informatics, Keck School of Medicine, University of Southern California, Marina del Rey, California, USA.
Dagmar TimmannCenter for Translational Neuro- and Behavioral Sciences (C-TNBS), Essen University Hospital, University of Duisburg-Essen, Essen, Germany.
David VaillancourtDepartment of Applied Physiology & Kinesiology, University of Florida, Gainesville, Florida, USA.ORCID https://orcid.org/0000-0002-0212-4950
Bart van de WarrenburgDepartment of Neurology, Donders Institute for Brain, Cognition, and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands.
Judith van GaalenDepartment of Neurology, Donders Institute for Brain, Cognition, and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands.
Xingang Wang7T Magnetic Resonance Imaging Translational Medical Center, Department of Radiology, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, China.
Philipp WegnerGerman Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
Sarah H YingDepartment of Radiology, Johns Hopkins University, Baltimore, Maryland, USA.
Ian H HardingQIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Carlos R Hernandez-CastilloFaculty of Computer Science, Dalhousie University, Halifax, Nova Scotia, Canada.ORCID https://orcid.org/0000-0003-1208-5577

Funding

Supplementary funding for U01NS104326 Clinical Trial Readiness for SCA1 and SCA3 (“READISCA”)U01NS104326 · NINDS · METHODIST HOSPITAL RESEARCH INSTITUTE · PI ASHIZAWA, TETSUO, OZ, GULIN · 2018 to 2022
$6.1M
Partnership for Magnetic Resonance Spectroscopy Biomarker Development-SupplementR01NS080816 · NINDS · UNIVERSITY OF MINNESOTA · PI OZ, GULIN · 2015 to 2019
$3.2M
Automatic Cerebellar MRI Labeling In Health and DiseaseR01NS056307 · NINDS · JOHNS HOPKINS UNIVERSITY · PI PRINCE, JERRY L · 2006 to 2015
$3.0M
Advanced Clinician Scientist Programme (ACCENT) 01EO2107Australian National Health and Medical Research Council Ideas Grant 1184403Australian National Health and Medical Research Council Investigator Grant 2026191Bundesministerium f r Bildung und ForschungCanada Research Chairs CRC-2020-00079EU Joint Programme Neurodegenerative Disease ResearchEuropean Reference Network for Rare Neurological DiseasesNational Ataxia Foundation Clinical Research ConsortiumNational Science Foundation EEC-1460674Natural Sciences and Engineering Research Council of Canada RGPIN-2022-034638NINDS NIH HHS R01 NS056307NINDS NIH HHS R01NS056307NINDS NIH HHS R01 NS080816NINDS NIH HHS R01NS080816NINDS NIH HHS U01 NS104326
6 · The paper itself

Abstract

backgroundSpinocerebellar ataxia type 3 (SCA3) is a rare, inherited neurodegenerative disease characterized by progressive loss of motor coordination.

objectivesWe 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.

methodsWhole-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.

resultsThe 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.

conclusionsCerebellar 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.

Indexed as

BrainMachado-Joseph DiseaseAdultAgedAtrophyCerebellumDisease ProgressionFemaleGray MatterHumansMagnetic Resonance ImagingMaleMiddle AgedSeverity of Illness IndexWhite MatterCerebrocerebellar connectivityFunctional brain networksNeurodegenerationSpinocerebellar AtaxiaVoxel‐based morphometry

Identifiers

PMID42108727
PMCPMC13518284

What OpenQuestion holds

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.