Clinical characteristics of patients with spinocerebellar ataxias 1, 2, 3 and 6 in the US; a prospective observational study

Orphanet Journal of Rare Diseases

SH Subramony⁴  Stefan M Pulst^1,14  John H Ferguson³  Amy Roberts Holbert⁶  David Cuthbertson⁶  Jeffrey P Krischer⁶  Pietro Mazzoni²  Guangbin Xia⁴  Michael D Geschwind^1,12  Sheng-Han Kuo²  Khalaf O Bushara⁸  Vikram G Shakkottai⁵  Henry L Paulson⁵  Theresa A Zesiewicz⁹  Sarah H Ying¹  Jeremy D Schmahmann^1,10  George R Wilmot^1,13  Christopher M Gomez⁷  Susan L Perlman^1,11  Karla P Figueroa^1,14  Tetsuo Ashizawa⁴ 

[1] Departments of Radiology, Neurology, and Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD, USA;Department of Neurology, Columbia University, New York, NY, USA;ORDR-NCATS, NIH, Bethesda, MD, USA;Department of Neurology and McKnight Brain Institute, University of Florida, 1149 S. Newell Dr., L3-100, Gainesville, FL 32611, USA;Department of Neurology, University of Michigan, Ann Arbor, MI, USA;Data Management Coordinating Center, University of South Florida, Tampa, FL, USA;Department of Neurology, University of Chicago, Chicago, IL, USA;Department of Neurology, University of Minnesota, Minneapolis, MN, USA;Department of Neurology, University of South Florida, Tampa, FL, USA;Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA;Department of Neurology, UCLA, Los Angeles, CA, USA;Department of Neurology, UCSF, San Francisco, CA, USA;Department of Neurology, Emory University, Atlanta, GA, USA;Department of Neurology, University of Utah, Salt Lake City, UT, USA

关键词: Progression rate;    SARA;    Natural history;    Spinocerebellar ataxia;   

Others  :  863423
DOI  :  10.1186/1750-1172-8-177

 received in 2013-08-28, accepted in 2013-10-30,  发布年份 2013

【 摘 要 】

Background

All spinocerebellar ataxias (SCAs) are rare diseases. SCA1, 2, 3 and 6 are the four most common SCAs, all caused by expanded polyglutamine-coding CAG repeats. Their pathomechanisms are becoming increasingly clear and well-designed clinical trials will be needed.

Methods

To characterize the clinical manifestations of spinocerebellar ataxia (SCA) 1, 2, 3 and 6 and their natural histories in the United States (US), we conducted a prospective multicenter study utilized a protocol identical to the European consortium study, using the Scale for the Assessment and Rating of Ataxia (SARA) score as the primary outcome, with follow-ups every 6 months up to 2 years.

Results

We enrolled 345 patients (60 SCA1, 75 SCA2, 138 SCA3 and 72 SCA6) at 12 US centers. SCA6 patients had a significantly later onset, and SCA2 patients showed greater upper-body ataxia than patients with the remaining SCAs. The annual increase of SARA score was greater in SCA1 patients (mean ± SE: 1.61 ± 0.41) than in SCA2 (0.71 ± 0.31), SCA3 (0.65 ± 0.24) and SCA6 (0.87 ± 0.28) patients (p = 0.049). The functional stage also worsened faster in SCA1 than in SCA2, 3 and 6 (p = 0.002).

Conclusions

The proportions of different SCA patients in US differ from those in the European consortium study, but as in the European patients, SCA1 progress faster than those with SCA2, 3 and 6. Later onset in SCA6 and greater upper body ataxia in SCA2 were noted. We conclude that progression rates of these SCAs were comparable between US and Europe cohorts, suggesting the feasibility of international collaborative clinical studies.

【 授权许可】

   
2013 Ashizawa et al.; licensee BioMed Central Ltd.

【 图 表 】

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