TY - JOUR
T1 - Clinical characteristics of patients with spinocerebellar ataxias 1, 2, 3 and 6 in the US; A prospective observational study
AU - Ashizawa, Tetsuo
AU - Figueroa, Karla P.
AU - Perlman, Susan L.
AU - Gomez, Christopher M.
AU - Wilmot, George R.
AU - Schmahmann, Jeremy D.
AU - Ying, Sarah H.
AU - Zesiewicz, Theresa A.
AU - Paulson, Henry L.
AU - Shakkottai, Vikram G.
AU - Bushara, Khalaf O.
AU - Kuo, Sheng Han
AU - Geschwind, Michael D.
AU - Xia, Guangbin
AU - Mazzoni, Pietro
AU - Krischer, Jeffrey P.
AU - Cuthbertson, David
AU - Holbert, Amy Roberts
AU - Ferguson, John H.
AU - Pulst, Stefan M.
AU - Subramony, Sh
N1 - Funding Information:
Dr. Geschwind receives grant funding from NIH/NIA ROI AG-031189 for his work on the early diagnosis of human prion disease, NIH/NIA AG031220, P01 Ago21601, and the Michael J. Homer Family Fund. Dr. Geschwind is a consultant for Lundbeck, Inc, MedaCorp, The Council of Advisors and Neurophage. Dr. Geschwind’s CJD-RPD research, not salary, is also supported by the UCSF MAC ADRC P50AG023501, NIH/NCRR UCSF-CTSI Grant Number UL1 RR024131, NIH/NIA AG021601, and NIH/NINDS Contract N01-NS-0-2328. Dr. Geschwind’s Huntington Disease research is supported by CHDI, Inc and NIH/NINDS (NS40068). Dr. Xia receives funding from Acorda Pharmaceutical (2013). Dr. Mazzoni reports no disclosures. Dr. Krischer receives NIH grant U54 NS064808 (2009-2014) Mr. Cuthbertson reports no disclosures. Ms. Roberts Holbert reports no disclosures. Dr. Ferguson reports no disclosures. Dr. Pulst receives grants from NIH (RC4NS073009; R21NS079852; R21NS081182, and RO1RO1NS33123; 2010-2015) and the National Ataxia Foundation (2013). Dr. Subramony receives honoraria and travel reimbursements from Athena diagnostics; compensation from Elsevier Co. for editing Handbook of Clinical Neurology, and received grants from National Ataxia Foundation (2011, 2012, 2013).
Funding Information:
Dr. Ashizawa was supported by NIH (RC1NS068897) for this work (2009-2012) and is receiving another NIH grant (R01NS083564) (2013-2018). He also receives research funding from the National Ataxia Foundation (2013) and the Muscular Dystrophy Association (2013-2015). He has been receiving royalty from Baylor College of Medicine (since 2001). He has received travel reimbursement from the Japanese Society of Neurology (2013), Cooperative Clinical Research Network–Friedreich Ataxia (2013), Muscular Dystrophy Foundation (2013), Central China University (with honorarium, 2012), Baylor College of Medicine (2012), Texas Neurological Society (2012), Unstable Microsatellites and Human Diseases (2011), Fudan University (with honorarium, 2011) and International Myotonic Dystrophy Consortium (2011). Ms. Figueroa reports no disclosures. Dr. Perlman received research grantS from Santhera Pharmaceuticals (2011), EDISON PHARMACEUTICALS (2012-13), FRIEDREICHS ATAXIA RESEARCH ALLIANCE (2002-2013), and National Ataxia Foundation (2013). Dr. Gomez receives NIH grant R01NS033202 (2010-2015). Dr. Wilmot is a member of the Data Safety Monitoring Board for Santhera Pharmaceuticals and has received support from the Cooperative Clinical Research Network–Friedreich Ataxia. Dr. Schmahmann reports no disclosures. Dr. Ying has been supported by NIH grants R21 NS059830, R01 EY019347, R01 NS056307, R21 EY022150, and received other research support from the Brain Science Institute and 5RC1NS068897. Dr. Zesiewicz Dr. Zesiewicz received compensation from UCB Pharma, Teva and GE for Speaking activities, grants from Astellas Pharmaceuticals, Baxter, Friedreich’s Ataxia Research Alliance, Takeda, Edison Pharmaceuticals, and GlaxoSmithKline for the past yer. Dr. Paulson is funded by NIH grants R01NS038712 (2009-2013), R01AG034228 (2009-2013), and R03NS072967 (2011-2013), has received license fee payments from Sirna Therapeutics (2007-2011), and received research contract support from Shire Human Genetic Therapy (2010-2012). Dr. Shakkottai receives NIH grant K08NS0.72158 (2010-2015), funding through the Dystonia Medical Research Foundation. Dr. Bushara reports no disclosures. Dr. Kuo receives NIH grant K08NS083738 (2013-2018) and Parkinson’s Disease Foundation CEI-1241. He also received Louis V Gerstner Jr. Scholar Award, and American Academy of Neurology research fellowship.
PY - 2013
Y1 - 2013
N2 - 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.
AB - 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.
KW - Natural history
KW - Progression rate
KW - SARA
KW - Spinocerebellar ataxia
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UR - http://www.scopus.com/inward/citedby.url?scp=84887345928&partnerID=8YFLogxK
U2 - 10.1186/1750-1172-8-177
DO - 10.1186/1750-1172-8-177
M3 - Article
C2 - 24225362
AN - SCOPUS:84887345928
SN - 1750-1172
VL - 8
JO - Orphanet Journal of Rare Diseases
JF - Orphanet Journal of Rare Diseases
IS - 1
M1 - 177
ER -