{"doi":"10.1002/mds.30143","title":"The Pattern and Stages of Atrophy in Spinocerebellar Ataxia Type 2: Volumetrics from <scp>ENIGMA</scp>‐Ataxia","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.","journal":"Movement Disorders","year":2025,"id":522703,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9476,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":471777,"name":"Isaac Adanyeguh","orcid":"0000-0003-1402-5877","position":1,"is_corresponding":false},{"id":241344,"name":"Benjamin Bender","orcid":"0000-0002-3205-4631","position":2,"is_corresponding":false},{"id":651417,"name":"Sylvia Boesch","orcid":"0000-0003-1657-7368","position":3,"is_corresponding":false},{"id":651418,"name":"Arturo Brunetti","orcid":"0000-0001-7057-3494","position":4,"is_corresponding":false},{"id":553912,"name":"Sirio Cocozza","orcid":"0000-0002-0300-5160","position":5,"is_corresponding":false},{"id":1226324,"name":"Léo Coutinho","orcid":"0000-0003-4921-2939","position":6,"is_corresponding":false},{"id":651420,"name":"Andreas Deistung","orcid":"0000-0002-2427-1302","position":7,"is_corresponding":false},{"id":631986,"name":"Stefano Diciotti","orcid":"0000-0001-8778-7819","position":8,"is_corresponding":false},{"id":651421,"name":"Imis Dogan","orcid":"0000-0002-6632-197X","position":9,"is_corresponding":false},{"id":17559,"name":"Alexandra Dürr","orcid":"0000-0002-8921-7104","position":10,"is_corresponding":false},{"id":1226325,"name":"Juan Fernández-Ruíz","orcid":"0000-0002-4038-0904","position":11,"is_corresponding":false},{"id":651424,"name":"Sophia Göricke","orcid":"0000-0003-1552-4475","position":12,"is_corresponding":false},{"id":328121,"name":"Marina Grisoli","orcid":"0000-0002-7663-446X","position":13,"is_corresponding":false},{"id":284110,"name":"Shuo Han","orcid":"0000-0003-2033-9004","position":14,"is_corresponding":false},{"id":1119214,"name":"Caterina Mariotti","orcid":"0000-0003-2405-3564","position":15,"is_corresponding":false},{"id":631981,"name":"Chiara Marzi","orcid":"0000-0002-1791-3573","position":16,"is_corresponding":false},{"id":241363,"name":"Mario Mascalchi","orcid":"0000-0002-5537-2982","position":17,"is_corresponding":false},{"id":274397,"name":"Fanny Mochel","orcid":"0000-0003-3970-3486","position":18,"is_corresponding":false},{"id":651430,"name":"Wolfgang Nachbauer","orcid":"0000-0001-8292-3690","position":19,"is_corresponding":false},{"id":1119208,"name":"Lorenzo Nanetti","orcid":"0000-0002-1952-4539","position":20,"is_corresponding":false},{"id":420959,"name":"Anna Nigri","orcid":"0000-0002-1197-5458","position":21,"is_corresponding":false},{"id":1226327,"name":"Sergio Eiji Ono","orcid":"0000-0001-7997-0189","position":22,"is_corresponding":false},{"id":233787,"name":"Chiadi U. 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