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

IF 7.6 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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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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2型脊髓小脑共济失调萎缩的模式和分期：来自enigma -共济失调的体积测量。

背景：脊髓小脑性共济失调2型（SCA2）是一种罕见的遗传性神经退行性疾病，其特征是运动协调和认知功能的进行性恶化。小脑、脑干和脊髓萎缩是SCA2的核心特征；然而，SCA2全脑萎缩的演变和模式尚不清楚。目的：我们进行了一项多部位结构磁共振成像（MRI）研究，以全面表征SCA2的神经变性特征。方法：对110名SCA2患者和128名对照组进行基于体素的形态学分析，以评估全脑容量的组间差异。还进行了与临床严重程度和基因型的相关性，以及不同疾病阶段萎缩模式的横断面分析。结果：SCA2与对照组相比，小脑白质（WM）、小脑中脚、脑桥和皮质脊髓束的萎缩最大（Cohen's d >2.5）。在小脑上、小脑下和脑梗中也有明显的非常大的影响（d bbb1.5）。在小脑灰质（GM）中，在运动协调和认知任务相关的区域观察到较大的影响（d >.8）。体积和疾病严重程度之间的强相关性（|r| > 0.4）很大程度上反映了这些分组结果。疾病严重程度分层表现出一种变性模式，始于临床前受试者的小脑和脑桥WM；扩散到小脑GM和脑-小脑/皮质脊髓WM束；最后在严重阶段涉及到丘脑，纹状体和皮层。结论：脑萎缩的程度和模式在SCA2过程中不断演变，广泛、不均匀地累及脑干、小脑束和小脑皮层；以及大脑皮层和纹状体的晚期病变。©2025作者。Wiley期刊有限责任公司代表国际帕金森和运动障碍学会出版的《运动障碍》。

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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.