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

Parkinsonism Relat Disord. 2017 Dec:45:75-80. doi: 10.1016/j.parkreldis.2017.10.007. Epub 2017 Oct 23.

Authors

Pei-Hsin Kuo¹, Shi-Rui Gan², Jie Wang³, Raymond Y Lo⁴, Karla P Figueroa⁵, Darya Tomishon⁶, Stefan M Pulst⁵, Susan Perlman⁷, George Wilmot⁸, Christopher M Gomez⁹, Jeremy D Schmahmann¹⁰, Henry Paulson¹¹, Vikram G Shakkottai¹¹, Sarah H Ying¹², Theresa Zesiewicz¹³, Khalaf Bushara¹⁴, Michael D Geschwind¹⁵, Guangbin Xia¹⁶, S H Subramony¹⁷, Tetsuo Ashizawa¹⁸, Sheng-Han Kuo¹⁹

Affiliations

¹ Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY, USA; Department of Neurology, Buddhist Tzu Chi General Hospital, Tzu Chi University, Hualien, Taiwan.
² Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY, USA; Department of Neurology, Institute of Neurology, First Affiliated Hospital of Fujian Medical University, Fujian Key Laboratory of Molecular Neurology, Fuzhou, China.
³ Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY, USA; Department of Fundamental and Community Nursing, School of Nursing, Nanjing Medical University, Nanjing, Jiangsu, China.
⁴ Department of Neurology, Buddhist Tzu Chi General Hospital, Tzu Chi University, Hualien, Taiwan.
⁵ Department of Neurology, University of Utah, Salt Lake City, UT, USA.
⁶ Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY, USA.
⁷ Department of Neurology, University of California, Los Angeles, CA, USA.
⁸ Department of Neurology, Emory University, Atlanta, GA, USA.
⁹ Department of Neurology, University of Chicago, Chicago, IL, USA.
¹⁰ Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
¹¹ Department of Neurology, University of Michigan, Ann Arbor, MI, USA.
¹² Department of Neurology, Johns Hopkins University, Baltimore, MD, USA.
¹³ Department of Neurology, University of South Florida, Tampa, FL, USA.
¹⁴ Department of Neurology, University of Minnesota, Minneapolis, MN, USA.
¹⁵ Department of Neurology, University of California, San Francisco, USA.
¹⁶ Department of Neurology, University of New Mexico, Albuquerque, NM, USA.
¹⁷ Department of Neurology, McKnight Brain Institute, University of Florida, Gainsville, FL, USA.
¹⁸ Houston Methodist Research Institute, Houston, TX, USA.
¹⁹ Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY, USA. Electronic address: sk3295@columbia.edu.

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.

MeSH terms

Adult
Cohort Studies
Disease Progression*
Dystonia / etiology*
Female
Humans
Male
Middle Aged
Spinocerebellar Ataxias / complications*
Spinocerebellar Ataxias / genetics*

Abstract

MeSH terms

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