The Pattern and Stages of Atrophy in Spinocerebellar Ataxia Type 2: Volumetrics from ENIGMA-Ataxia

IF 7.4 1区医学 Q1 CLINICAL NEUROLOGY

Movement Disorders Pub Date : 2025-02-10 DOI:10.1002/mds.30143

Jason W. Robertson PhD, Isaac Adanyeguh PhD, Benjamin Bender PhD, Sylvia Boesch MD, MSc, Arturo Brunetti MD, Sirio Cocozza MD, PhD, Léo Coutinho MD, Andreas Deistung PhD, Stefano Diciotti PhD, Imis Dogan PhD, Alexandra Durr MD, PhD, Juan Fernandez-Ruiz PhD, Sophia L. Göricke MD, Marina Grisoli MD, Shuo Han PhD, Caterina Mariotti MD, Chiara Marzi PhD, Mario Mascalchi MD, PhD, Fanny Mochel MD, PhD, Wolfgang Nachbauer MD, PhD, Lorenzo Nanetti MD, Anna Nigri PhD, Sergio E. Ono MD, PhD, Chiadi U. Onyike MD, Jerry L. Prince PhD, Kathrin Reetz MD, Sandro Romanzetti PhD, Francesco Saccà MD, PhD, Matthis Synofzik MD, Hélio A. Ghizoni Teive MD, PhD, Sophia I. Thomopoulos BA, Paul M. Thompson PhD, Dagmar Timmann MD, Sarah H. Ying MD, Ian H. Harding PhD, Carlos R. Hernandez-Castillo PhD

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引用次数: 0

Abstract

Background

Spinocerebellar ataxia type 2 (SCA2) is a rare, inherited neurodegenerative disease characterized by progressive deterioration in both motor coordination and cognitive function. Atrophy of the cerebellum, brainstem, and spinal cord are core features of SCA2; however, the evolution and pattern of whole-brain atrophy in SCA2 remain unclear.

Objective

We undertook a multisite, structural magnetic resonance imaging (MRI) study to comprehensively characterize the neurodegeneration profile of SCA2.

Methods

Voxel-based morphometry analyses of 110 participants with SCA2 and 128 controls were undertaken to assess groupwise differences in whole-brain volume. Correlations with clinical severity and genotype, and cross-sectional profiling of atrophy patterns at different disease stages, were also performed.

Results

Atrophy in SCA2 versus controls was greatest (Cohen's d >2.5) in the cerebellar white matter (WM), middle cerebellar peduncle, pons, and corticospinal tract. Very large effects (d >1.5) were also evident in the superior cerebellar, inferior cerebellar, and cerebral peduncles. In the cerebellar gray matter (GM), large effects (d >0.8) were observed in areas related to both motor coordination and cognitive tasks. Strong correlations (|r| > 0.4) between volume and disease severity largely mirrored these groupwise outcomes. Stratification by disease severity exhibited a degeneration pattern beginning in the cerebellar and pontine WM in preclinical subjects; spreading to the cerebellar GM and cerebro-cerebellar/corticospinal WM tracts; and then finally involving the thalamus, striatum, and cortex in severe stages.

Conclusion

The magnitude and pattern of brain atrophy evolve over the course of SCA2, with widespread, nonuniform involvement across the brainstem, cerebellar tracts, and cerebellar cortex; and late involvement of the cerebral cortex and striatum. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

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来源期刊

Movement Disorders 医学-临床神经学

CiteScore

13.30

自引率

8.10%

发文量

371

审稿时长

12 months

期刊介绍： Movement Disorders publishes a variety of content types including Reviews, Viewpoints, Full Length Articles, Historical Reports, Brief Reports, and Letters. The journal considers original manuscripts on topics related to the diagnosis, therapeutics, pharmacology, biochemistry, physiology, etiology, genetics, and epidemiology of movement disorders. Appropriate topics include Parkinsonism, Chorea, Tremors, Dystonia, Myoclonus, Tics, Tardive Dyskinesia, Spasticity, and Ataxia.