Dystonia and ataxia progression in spinocerebellar ataxias

Pei Hsin Kuo; Shi Rui Gan; Jie Wang; Raymond Y. Lo; Karla P. Figueroa; Darya Tomishon; Stefan M. Pulst; Susan Perlman; George Wilmot; Christopher M. Gomez; Jeremy D. Schmahmann; Henry Paulson; Vikram G. Shakkottai; Sarah H. Ying; Theresa Zesiewicz; Khalaf Bushara; Michael D. Geschwind; Guangbin Xia; S. H. Subramony; Tetsuo Ashizawa; Sheng Han Kuo

doi:10.1016/j.parkreldis.2017.10.007

Dystonia and ataxia progression in spinocerebellar ataxias

Pei Hsin Kuo, Shi Rui Gan, Jie Wang, Raymond Y. Lo, Karla P. Figueroa, Darya Tomishon, Stefan M. Pulst, Susan Perlman, George Wilmot, Christopher M. Gomez, Jeremy D. Schmahmann, Henry Paulson, Vikram G. Shakkottai, Sarah H. Ying, Theresa Zesiewicz, Khalaf Bushara, Michael D. Geschwind, Guangbin Xia, S. H. Subramony, Tetsuo AshizawaSheng Han Kuo

Research output: Contribution to journal › Article › peer-review

36 Scopus citations

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.

Original language	English (US)
Pages (from-to)	75-80
Number of pages	6
Journal	Parkinsonism and Related Disorders
Volume	45
DOIs	https://doi.org/10.1016/j.parkreldis.2017.10.007
State	Published - Dec 2017
Externally published	Yes

Keywords

Dystonia
Modifier
Spinocerebellar ataxia
Trinucleotide repeat

ASJC Scopus subject areas

Neurology
Geriatrics and Gerontology
Clinical Neurology

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10.1016/j.parkreldis.2017.10.007

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Kuo, P. H., Gan, S. R., Wang, J., Lo, R. Y., Figueroa, K. P., Tomishon, D., Pulst, S. M., Perlman, S., Wilmot, G., Gomez, C. M., Schmahmann, J. D., Paulson, H., Shakkottai, V. G., Ying, S. H., Zesiewicz, T., Bushara, K., Geschwind, M. D., Xia, G., Subramony, S. H., ... Kuo, S. H. (2017). Dystonia and ataxia progression in spinocerebellar ataxias. Parkinsonism and Related Disorders, 45, 75-80. https://doi.org/10.1016/j.parkreldis.2017.10.007

Kuo, PH, Gan, SR, Wang, J, Lo, RY, Figueroa, KP, Tomishon, D, Pulst, SM, Perlman, S, Wilmot, G, Gomez, CM, Schmahmann, JD, Paulson, H, Shakkottai, VG, Ying, SH, Zesiewicz, T, Bushara, K, Geschwind, MD, Xia, G, Subramony, SH, Ashizawa, T & Kuo, SH 2017, 'Dystonia and ataxia progression in spinocerebellar ataxias', Parkinsonism and Related Disorders, vol. 45, pp. 75-80. https://doi.org/10.1016/j.parkreldis.2017.10.007

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title = "Dystonia and ataxia progression in spinocerebellar ataxias",

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.",

keywords = "Dystonia, Modifier, Spinocerebellar ataxia, Trinucleotide repeat",

author = "Kuo, {Pei Hsin} and Gan, {Shi Rui} and Jie Wang and Lo, {Raymond Y.} and Figueroa, {Karla P.} and Darya Tomishon and Pulst, {Stefan M.} and Susan Perlman and George Wilmot and Gomez, {Christopher M.} and Schmahmann, {Jeremy D.} and Henry Paulson and Shakkottai, {Vikram G.} and Ying, {Sarah H.} and Theresa Zesiewicz and Khalaf Bushara and Geschwind, {Michael D.} and Guangbin Xia and Subramony, {S. H.} and Tetsuo Ashizawa and Kuo, {Sheng Han}",

note = "Publisher Copyright: {\textcopyright} 2017 Elsevier Ltd",

year = "2017",

month = dec,

doi = "10.1016/j.parkreldis.2017.10.007",

language = "English (US)",

volume = "45",

pages = "75--80",

journal = "Parkinsonism and Related Disorders",

issn = "1353-8020",

publisher = "Elsevier BV",

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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

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 -

Dystonia and ataxia progression in spinocerebellar ataxias

Abstract

Keywords

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