ArticleJournal of neurology2025
Regional brain atrophy subtypes in spinocerebellar ataxia type 3: links to clinical performance and treatment response.
Article in Journal of neurology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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Who cites it
1 citing paper in PubMed.
- Unveiling the Clinical Impact of Lower Limb Robotic Devices in Neurorehabilitation: An Umbrella Review.Annals of biomedical engineering · 2026Review
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Authors and funding
13 authors.
Funding
Abstract
Spinocerebellar ataxia type 3 (SCA3) is characterized by strong phenotypic heterogeneity, underscoring the need to explore subtypes using objective structural neuroimaging approaches. Identifying neuroimaging heterogeneity in SCA3 could help inform the prognosis and guide the development of personalized interventions. Here, we calculated gray matter volumes using voxel-based morphometry from 3D T1-weighted magnetic resonance images across two independent cohorts (discovery cohort: n = 222; replication cohort: n = 90). Non-negative matrix factorization was used to identify atrophy subtypes in SCA3. An independent cohort of 29 patients with SCA3, who underwent repetitive transcranial magnetic stimulation (rTMS), was used to explore the treatment effects across subtypes. Two atrophy subtypes were identified: subtype1 (ST1) was characterized by predominant involvement of the basal ganglia, with mild cerebellar and cortical deficits, and subtype2 (ST2) was characterized by severe cerebellar atrophy with neostriatal atrophy and thalamic subregion hypertrophy. These results were replicated in the subtype validation cohort. The ST1 atrophy pattern correlated with the International Cooperative Ataxia Rating Scale (ICARS) kinetic function subscale scores, whereas the ST2 atrophy pattern correlated with the ICARS posture and gait scores. Exploratory analysis of longitudinal data from the rTMS cohort revealed significant overall clinical improvement, but no statistically significant interaction between subtype and treatment response was detected, despite the observation of promising subtype-specific patterns of improvement. These findings suggest that patients with SCA3 have robust structural atrophy subtypes, which may provide a new framework for stratifying patients in future clinical and therapeutic research.
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