Dystonia and ataxia progression in spinocerebellar ataxias

• Authors: Pei-Hsin Kuo, Columbia University; Shi-Rui Gan, Columbia University; Jie Wang, Columbia University; Raymond Y. Lo, Tzu Chi University; Karla P. Figueroa, University of Utah; Darya Tomishon, Columbia University; Stefan M. Pulst, University of Utah; Susan Perlman, University of California; George (Chip) Wilmot, Emory University; Christopher M. Gomez, University of Chicago; Jeremy D. Schmahmann, Harvard University; Henry Paulson, University of Michigan; Vikram G. Shakkottai, University of Michigan; Sarah H. Ying, Johns Hopkins University; Theresa Zesiewicz, University of South Florida; Khalaf Bushara, University of Minnesota; Michael D. Geschwind, University of California; Guangbin Xia, University of New Mexico; S.H. Subramony, University of Florida; Tetsuo Ashizawa, Houston Methodist Research Institute; Sheng-Han Kuo, Columbia University
• Journal Title: Parkinsonism and Related Disorders
• Volume: Volume 45
• Publisher: Elsevier | 2017-12-01, Pages 75-80
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1016/j.parkreldis.2017.10.007
• Subjects: Biology, Neuroscience
• Keywords: Science & Technology; Life Sciences & Biomedicine; Clinical Neurology; Neurosciences & Neurology; Spinocerebellar ataxia; Dystonia; Trinucleotide repeat; Modifier; MACHADO-JOSEPH-DISEASE; MOVEMENT-DISORDERS; CEREBELLUM; TYPE-1; SUBTYPES; PROFILE; COHORT; GENES

Abstract

Background Dystonia is a common feature in spinocerebellar ataxias (SCAs). Whether the presence of dystonia is associated with different rate of ataxia progression is not known. Objectives To study clinical characteristics and ataxia progression in SCAs with and without dystonia. Methods We studied 334 participants with SCA 1, 2, 3 and 6 from the Clinical Research Consortium for Spinocerebellar Ataxias (CRC-SCA) and compared the clinical characteristics of SCAs with and without dystonia. We repeatedly measured ataxia progression by the Scale for Assessment and Rating of Ataxia every 6 months for 2 years. Regression models were employed to study the association between dystonia and ataxia progression after adjusting for age, sex and pathological CAG repeats. We used logistic regression to analyze the impact of different repeat expansion genes on dystonia in SCAs. Results Dystonia was most commonly observed in SCA3, followed by SCA2, SCA1, and SCA6. Dystonia was associated with longer CAG repeats in SCA3. The CAG repeat number in TBP normal alleles appeared to modify the presence of dystonia in SCA1. The presence of dystonia was associated with higher SARA scores in SCA1, 2, and 3. Although relatively rare in SCA6, the presence of dystonia was associated with slower progression of ataxia. Conclusions The presence of dystonia is associated with greater severity of ataxia in SCA1, 2, and 3, but predictive of a slower progression in SCA6. Complex genetic interactions among repeat expansion genes can lead to diverse clinical symptoms and progression in SCAs.