The Pattern and Staging of Brain Atrophy in Spinocerebellar Ataxia Type 2 (SCA2): MRI Volumetrics from ENIGMA-Ataxia

• Published in: bioRxiv
• Main Authors: Robertson, Jason W, Adanyeguh, Isaac, Bender, Benjamin, Boesch, Sylvia, Brunetti, Arturo, Cocozza, Sirio, Coutinho, Léo, Deistung, Andreas, Diciotti, Stefano, Dogan, Imis, Durr, Alexandra, Fernandez-Ruiz, Juan, Göricke, Sophia L, Grisoli, Marina, Han, Shuo, Mariotti, Caterina, Marzi, Chiara, Mascalchi, Mario, Mochel, Fanny, Nachbauer, Wolfgang, Nanetti, Lorenzo, Nigri, Anna, Ono, Sergio E, Onyike, Chiadi U, Prince, Jerry L, Reetz, Kathrin, Romanzetti, Sandro, Saccà, Francesco, Synofzik, Matthis, Ghizoni Teive, Hélio A, Thomopoulos, Sophia I, Thompson, Paul M, Timmann, Dagmar, Ying, Sarah H, Harding, Ian H, Hernandez-Castillo, Carlos R
• Format: Journal Article
• Language: English
• Published: United States Cold Spring Harbor Laboratory 17.09.2024
• ISSN: 2692-8205; 2692-8205
• DOI: 10.1101/2024.09.16.613281

Spinocerebellar ataxia type 2 (SCA2) is a rare, inherited neurodegenerative disease characterised 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. We undertook a multi-site, structural magnetic resonance imaging (MRI) study to comprehensively characterize the neurodegeneration profile of SCA2. 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. Atrophy in SCA2 relative to controls was greatest (Cohen's >2.5) in the cerebellar white matter (WM), middle cerebellar peduncle, pons, and corticospinal tract. Very large effects ( >1.5) were also evident in the superior cerebellar, inferior cerebellar, and cerebral peduncles. In cerebellar grey matter (GM), large effects ( >0.8) mapped to areas related to both motor coordination and cognitive tasks. Strong correlations (| |>0.4) between volume and disease severity largely mirrored these groupwise outcomes. Stratification by disease severity showed a degeneration pattern beginning in cerebellar and pontine WM in pre-clinical subjects; spreading to the cerebellar GM and cerebro-cerebellar/corticospinal WM tracts; then finally involving the thalamus, striatum, and cortex in severe stages. The magnitude and pattern of brain atrophy evolves over the course of SCA2, with widespread, non-uniform involvement across the brainstem, cerebellar tracts, and cerebellar cortex; and late involvement of the cerebral cortex and striatum.