TY - JOUR
T1 - Dystonia and ataxia progression in spinocerebellar ataxias
AU - Kuo, Pei Hsin
AU - Gan, Shi Rui
AU - Wang, Jie
AU - Lo, Raymond Y.
AU - Figueroa, Karla P.
AU - Tomishon, Darya
AU - Pulst, Stefan M.
AU - Perlman, Susan
AU - Wilmot, George
AU - Gomez, Christopher M.
AU - Schmahmann, Jeremy D.
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:
The CRC-SCA natural history study is supported by the Rare Disease Clinical Research Network (RDCRN) ( RC1NS068897 ), and the National Ataxia Foundation . Dr. Kuo has received funding from NINDS K08 NS08738 (principal investigator), Louis V. Gerstner Jr. Scholar Award, Parkinson's Disease Foundation , American Academy of Neurology Research Fellowship , American Parkinson's Disease Association ( PG008011 ), International Essential Tremor Foundation , NIEHS pilot award ES009089 , and the Smart Foundation . The natural history study of spinocerebellar ataxias is supported by the Rare Disease Clinical Research Network (RDCRN) ( RC1NS068897 ).
Funding Information:
Dr. Zesiewicz has served as a clinical advisor for Steminent Biotherapeutics, and she has received travel reimbursement from the department of neurology at University of Southern Florida; has received travel reimbursement for a Biohaven Pharmaceuticals meeting. Dr. Zesiewicz has served on the editorial board for Neurodegenerative Disease Management and Tremor and other Hyperkinetic Movements , and has received research support for her division for approximately 20 clinical trials for Parkinson's disease, Friedreich's ataxia, and spinocerebellar ataxias. Dr. Zesiewicz's division is a site in a multi-site trial of Parkinson's disease patients with the LRRK2 mutation and is sponsored by the National Institutes of Health but funded by Emory University. The rest authors report no conflicts of interest.
Publisher Copyright:
© 2017 Elsevier Ltd
PY - 2017/12
Y1 - 2017/12
N2 - 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.
AB - 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.
KW - Dystonia
KW - Modifier
KW - Spinocerebellar ataxia
KW - Trinucleotide repeat
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U2 - 10.1016/j.parkreldis.2017.10.007
DO - 10.1016/j.parkreldis.2017.10.007
M3 - Article
C2 - 29089256
AN - SCOPUS:85032338864
SN - 1353-8020
VL - 45
SP - 75
EP - 80
JO - Parkinsonism and Related Disorders
JF - Parkinsonism and Related Disorders
ER -