TY - JOUR
T1 - Postural tremor and ataxia progression in spinocerebellar ataxias
AU - Gan, Shi Rui
AU - Wang, Jie
AU - Figueroa, Karla P.
AU - Pulst, Stefan M.
AU - Tomishon, Darya
AU - Lee, Danielle
AU - Perlman, Susan
AU - Wilmot, George
AU - Gomez, Christopher M.
AU - Schmahmann, Jeremy
AU - Paulson, Henry
AU - Shakkottai, Vikram G.
AU - Ying, Sarah H.
AU - Zesiewicz, Theresa
AU - Bushara, Khalaf
AU - Geschwind, Michael D.
AU - Xia, Guangbin
AU - Subramony, S. H.
AU - Ashizawa, Tetsuo
AU - Kuo, Sheng Han
N1 - Funding Information:
* To whom correspondence should be addressed. E-mail: sk3295@columbia.edu Editor: Elan D. Louis, Yale University, USA Received: July 7, 2017 Accepted: September 7, 2017 Published: October 9, 2017 Copyright: ’ 2017 Gan et al. This is an open-access article distributed under the terms of the Creative Commons Attribution–Noncommercial–No Derivatives License, which permits the user to copy, distribute, and transmit the work provided that the original authors and source are credited; that no commercial use is made of the work; and that the work is not altered or transformed. Funding: The CRC-SCA natural history study is supported by the Rare Disease Clinical Research Network (RDCRN) (RC1NS068897) and the National Ataxia Foundation. 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. Dr. Gan is supported by the National Natural Science Foundation of China (U1505222). Financial Disclosures: Dr. Zesiewicz has served as a clinical advisor for Steminent Biotherapeutic. She has received travel reimbursement from the Department of Neurology at University of Southern Florida for a Biohaven Pharmaceuticals meeting. Dr. Zesiewicz has also served on the editorial boards for Neurodegenerative Disease Management and Tremor and Other Hyperkinetic Movements. Dr. Zesiewicz has received research support for approximately 20 clinical trials for Parkinson’s disease, Friedreich’s ataxia, and spinocerebellar ataxias. Conflicts of interest: The authors report no conflict of interest. Ethics Statement: This study was performed in accordance with the ethical standards detailed in the Declaration of Helsinki. The authors’ institutional ethics committee has approved this study and all patients have provided written informed consent.
Publisher Copyright:
© 2017 Gan et al.
PY - 2017/10/9
Y1 - 2017/10/9
N2 - 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.
AB - 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.
KW - Cerebellum
KW - Genetics
KW - Neurodegeneration
KW - Postural tremor
KW - Spinocerebellar ataxias
UR - http://www.scopus.com/inward/record.url?scp=85031301193&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85031301193&partnerID=8YFLogxK
U2 - 10.7916/D8GM8KRH
DO - 10.7916/D8GM8KRH
M3 - Article
C2 - 29057148
AN - SCOPUS:85031301193
SN - 2160-8288
VL - 7
JO - Tremor and Other Hyperkinetic Movements
JF - Tremor and Other Hyperkinetic Movements
ER -