Postural tremor and ataxia progression in spinocerebellar ataxias

• Type of Material: Article
• Authors: Shi-Rui Gan, Columbia University; Jie Wang, Columbia University; Karla P. Figueroa, University of Utah; Stefan M. Pulst, University of Utah; Darya Tomishon, Columbia University; Danielle Lee, Columbia University; Susan Perlman, University of California, Los Angeles; George Wilmot, Emory University; Christopher M. Gomez, University of Chicago Hospitals; Jeremy Schmahmann, Massachusetts General Hospital; Henry Paulson, University Michigan Ann Arbor; Vikram G. Shakkottai, University Michigan Ann Arbor; Sarah H. Ying, Johns Hopkins University; Theresa Zesiewicz, University of South Florida; Khalaf Bushara, University of Minnesota; Michael D. Geschwind, University of California, San Francisco; Guangbin Xia, University of New Mexico; S. H. Subramony, University of New Mexico; Tetsuo Ashizawa, Methodist Hospital Houston; Sheng-Han Kuo, Columbia University
• Language: English
• Date: 2017-10-09
• Publisher: Columbia University, Library/Information Service, Center for Digital Research and Scholarship: Creative Commons Attribution Non-Commercial No Derivatives
• Publication Version: Final Published Version
• Copyright Statement: © 2017 Gan et al.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.7916/D8GM8KRH
• Title of Journal or Parent Work: Tremor and Other Hyperkinetic Movements
• ISSN: 2160-8288
• Volume: 7
• Start Page: 492
• End Page: 492
• Grant/Funding Information: Dr. Gan is supported by the National Natural Science Foundation of China (U1505222).; Dr. Kuo is supported by the NINDS K08 NS083738, Louis V. Gerstner Jr. Scholarship, American Brain Research Training Fellowship, Parkinson’s Disease Foundation, American Parkinson’s Disease Association, Rare Disease Clinical Research Network (RDCRN) (RC1NS068897), International Essential Tremor Foundation, the Smart Foundation, NIEHS pilot grant ES009089.; The CRC-SCA natural history study is supported by the Rare Disease Clinical Research Network (RDCRN) (RC1NS068897) and the National Ataxia Foundation.
• Keywords: Spinocerebellar ataxias; genetics; neurodegeneration; postural tremor; cerebellum
• Research Categories: Biology, Neuroscience

Abstract

Background: Postural tremor can sometimes occur in spinocerebellar ataxias (SCAs). However, the prevalence and clinical characteristics of postural tremor in SCAs are poorly understood, and whether SCA patients with postural tremor have different ataxia progression is not known. Methods: We studied postural tremor in 315 patients with SCA1, 2, 3, and 6 recruited from the Clinical Research Consortium for Spinocerebellar Ataxias (CRC-SCA), which consists of 12 participating centers in the United States, and we evaluated ataxia progression in these patients from January 2010 to August 2012. Results: Among 315 SCA patients, postural tremor was most common in SCA2 patients (SCA1, 5.8%; SCA2, 27.5%; SCA3, 12.4%; SCA6, 16.9%; p = 0.007). SCA3 patients with postural tremor had longer CAG repeat expansions than SCA3 patients without postural tremor (73.67 ± 3.12 vs. 70.42 ± 3.96, p = 0.003). Interestingly, SCA1 and SCA6 patients with postural tremor had a slower rate of ataxia progression (SCA1, β = –0.91, p < 0.001; SCA6, β = –1.28, p = 0.025), while SCA2 patients with postural tremor had a faster rate of ataxia progression (β =5 1.54, p = 0.034).We also found that the presence of postural tremor in SCA2 patients could be influenced by repeat expansions of ATXN1 (β = –1.53, p = 0.037) and ATXN3 (β = 0.57, p = 0.018), whereas postural tremor in SCA3 was associated with repeat lengths in TBP (β = 0.63, p = 0.041) and PPP2R2B (β = –0.40, p = 0.032). Discussion: Postural tremor could be a clinical feature of SCAs, and the presence of postural tremor could be associated with different rates of ataxia progression. Genetic interactions between ataxia genes might influence the brain circuitry and thus affect the clinical presentation of postural tremor.