| Contributors: |
Robertson, J. W.; Adanyeguh, I.; Bender, B.; Boesch, S.; Brunetti, A.; Cocozza, S.; Coutinho, L.; Deistung, A.; Diciotti, S.; Dogan, I.; Durr, A.; Fernandez-Ruiz, J.; Goricke, S. L.; Grisoli, M.; Han, S.; Mariotti, C.; Marzi, C.; Mascalchi, M.; Mochel, F.; Nachbauer, W.; Nanetti, L.; Nigri, A.; Ono, S. E.; Onyike, C. U.; Prince, J. L.; Reetz, K.; Romanzetti, S.; Sacca, F.; Synofzik, M.; Teive, H. A. G.; Thomopoulos, S. I.; Thompson, P. M.; Timmann, D.; Ying, S. H.; Harding, I. H.; Hernandez-Castillo, C. R. |
| Description: |
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 ... |