The Initial Symptom and Motor Progression in Spinocerebellar Ataxias

• Type of Material: Article
• Authors: Lan Luo, Columbia University; Jie Wang, Nanjing Medical University; Raymond Y Lo, Buddhist Tzu Chi General Hospital; Karla P Figueroa, University of Utah; Stefan M Pulst, University of Utah; Pei-Hsin Kuo, Columbia University; Susan Perlman, University of California Los Angeles; George (Chip) Wilmot, Emory University; Christopher M Gomez, University of Chicago; Jeremy Schmahmann, Massachusetts General Hospital; Henry Paulson, University of Michigan; Vikram Shakkottai, University of Michigan; Sarah H Ying, Johns Hopkins University; Theresa Zesiewicz, University of South Florida; Khalaf Bushara, University of Minnesota; Michael Geschwind, University of California Los Angeles; Guangbin Xia, University of Florida; SH Subramony, University of Florida; Tetsuo Ashizawa, Houston Methodist Research Institute; Sheng-Han Kuo, Columbia University
• Language: English
• Date: 2017-06-01
• Publisher: Springer Verlag (Germany)
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2016, Springer Science+Business Media New York.
• Final Published Version (URL): http://dx.doi.org/10.1007/s12311-016-0836-3
• Title of Journal or Parent Work: Cerebellum
• ISSN: 1473-4222
• Volume: 16
• Issue: 3
• Start Page: 615
• End Page: 622
• Grant/Funding Information: NINDS K08 NS083738, Louis V. Gerstner Jr. Scholarship, American Brain Research Training Fellowship, Parkinson Disease Foundation, American Parkinson's Disease Association, Rare Disease Clinical Research Network (RDCRN) (RC1NS068897), International Essential Tremor Foundation, and NIEHS pilot grant ES009089, the Smart Foundation, Jiangsu Government Scholarship for Overseas Studies, Qing Lan Project, and the Key Discipline Development Project (JX10617801) of Jiangsu Province, China.
• Keywords: Life Sciences & Biomedicine; Science & Technology; TYPE-1; Neurodegeneration; COHORT; Spinocerebellar ataxias; PARKINSON-DISEASE; PATHOGENESIS; Neurosciences & Neurology; Cerebellum; Neurosciences; DEPRESSION; Subtypes; DOMINANT CEREBELLAR ATAXIAS; SUBTYPES
• Research Categories: Health Sciences, Medicine and Surgery; Biology, Neuroscience

Abstract

The aim of this study is to determine whether the initial symptom associates with motor progression in spinocerebellar ataxias (SCAs). SCAs are clinically heterogeneous and the initial presentation may represent different subtypes of SCA with different motor progression. We studied 317 participants with SCAs1, 2, 3, and 6 from the Clinical Research Consortium for SCAs (CRC-SCA) and repeatedly measured the severity of ataxia for 2 years. SCA patients were divided into gait-onset and non-gait-onset (speech, vision, and hand dexterity) groups based on the initial presentation. In addition to demographic comparison, we employed regression models to study ataxia progression in these two groups after adjusting for age, sex, and pathological CAG repeats. The majority of SCA patients had gait abnormality as an initial presentation. The pathological CAG repeat expansions were similar between the gait-onset and non-gait-onset groups. In SCA1, gait-onset group progressed slower than non-gait-onset group, while gait-onset SCA6 group progressed faster than their counterpart. In addition, the disease presented 9 years later for SCA2 gait-onset group than non-gait-onset group. Initial symptoms of SCA3 did not influence age of onset or disease progression. The initial symptom in each SCA has a different influence on age of onset and motor progression. Therefore, gait and non-gait-onset groups of SCAs might represent different subtypes of the diseases.