Movement Disorders in Autosomal Dominant Spinocerebellar Ataxias: A Prospective Multicenter NIH Cohort Study (S43.001)

OBJECTIVE: To prospectively characterize the type of extra-cerebellar movement disorders and their determinants in a large cohort of spinocerebellar ataxia (SCA) subjects. BACKGROUND: SCA9s are a genetically, clinically, and pathologically heterogeneous group of neurodegenerative disorders that typically involve cerebellar and extra-cerebellar structures. Various movement disorders (MD9s) occur with some frequency in the SCA9s and their characterization and treatment can impact outcome. DESIGN/METHODS: We prospectively collected data on patients with SCA 1, 2, 3 and 6 from 12 centers in the US (Clinical Research Consortium for Spinocerebellar Ataxias /CRC-SCA). Patient characteristics, neurological rating (SARA), and functional status were assessed. Prevalence of dystonia, chorea, rigidity, postural tremor, rest tremor, and myoclonus and potential factors contributing to them were analyzed. The size of the responsible CAG repeat in the expanded allele was determined. RESULTS: A total of 301 patients, including 52 SCA 1, 64 SCA 2, 117 SCA 3, and 68 SCA 6 patients were examined. Forty % (119) had one or more SCA associated MD9s (rigidity, tremor, myoclonus, chorea, dystonia). Postural tremor was the most frequent MD (2 to 31% of different SCA9s) followed by rigidity and dystonia. A combination of rigidity and tremor was observed in SCA 2, SCA 3 and SCA 6 (6 to 12% of the cases) but not in SCA 1. Chorea was most frequent in SCA 2 and dystonia, in SCA 2 and 3. MD9s were in general associated with more severe disease measures; and in SCA 3 age at onset, disease duration and repeat size. CONCLUSIONS: Movement disorders are quite prevalent in SCA9s; postural tremor was most frequent followed by dystonia and rigidity. They often occur with more severe disease and may contribute to disability. Their recognition may facilitate genotypic diagnosis and allow symptomatic therapy. Factors determining their presence need better definition. Supported by: NIH/NINDS: 1RC1NS068897-01 (ARRA). Disclosure: Dr. Moscovich has nothing to disclose. Dr. Okun has received personal compensation for activities with the National Parkinson Foundation and Ask the Expert. Dr. Okun has received royalty payments from Demos, Humana, and Cambridge. Dr. Okun has received research support from the Michael J. Fox Foundation, the National Parkinson Foundation, the Parkinson Alliance, the Smallwood Foundation, and the National Institutes of Health. Dr. Favilla has nothing to disclose. Dr. Figueroa has nothing to disclose. Dr. Pulst has received personal compensation for activities with Athena Diagnostics. Dr. Pulst has received license or royalty payments from Cedars-Sinai Medical Center. Dr. Perlman has received research support from Santhera Pharmaceuticals. Dr. Wilmot has nothing to disclose. Dr. Gomez has nothing to disclose. Dr. Schmahmann has nothing to disclose. Dr. Ying has nothing to disclose. Dr. Paulson has received personal compensation for activities with Shire. Dr. Paulson has received license fee payments from Sirna Therapeutics. Dr. Paulson has received research support from Shire. Dr. Shakkottai has nothing to disclose. Dr. Bushara has nothing to disclose. Dr. Zesiewicz has received personal compensation for activities with Teva Neuroscience, GE, ProCE, and UCB Pharma as a speaker. Dr. Zesiewicz has received research support from Friedreich9s Ataxia Research Alliance, Allon Pharmaceuticals, GlaxoSmithKline, Inc. and UCB Pharma. Dr. Zesiewicz has received research support from Friedreich9s Ataxia Research Alliance. Dr. Kuo has nothing to disclose. Dr. Beaulieu has nothing to disclose. Dr. Xia has nothing to disclose. Dr. Ashizawa has received royalty payments from Baylor College of Medicine. Dr. Subramony has received personal compensation for activities with Athena as speaker.