Objective: The present study was aimed to assess the progression of saccade involvement in SCA2 patients, identify its main determinants and evaluate its usefulness as outcome measures in clinical trials.

Background: Saccadic eye movement abnormalities are frequent features of Spinocerebellar Ataxia type 2 (SCA2) patients [1,2]. Nevertheless the natural history of these alterations is unknown, limiting its helpfulness as outcome measure for clinical trials.

Methods: We performed a prospective 5-year follow-up study of saccadic abnormalities in 30 SCA2 patients and their sex-and age-matched healthy controls. All subjects were evaluated a total of four times by clinical and electrooculographical assessments of horizontal saccades and by Scale for Assessing and Rating of Ataxia (SARA).

Results: SCA2 patients showed significant decreases in saccade peak velocity and saccade accuracy, and increases of saccadic latency during the follow-up period. Annual progression rates were significantly higher in patients compared to controls. Faster progression rates of saccade slowing were associated with higher trinucleotide CAG-repeat expansions. Sample size estimates for two-arm trials would require 19 patients per group to detect a 50% reduction in disease progression using saccade peak velocity as outcome variable, but 44 and 124 patients using saccade latency and accuracy, respectively (power, 80%; alpha=0.05). The same analysis applied to the SARA score in our cohort revealed an estimation of 70 subjects per group.

Conclusions: Electrooculographical measures of saccade changes are useful for the objective quantification of disease course in SCA2. The progression rate of saccade slowing is highly influenced by the CAG-repeat expansion size, providing novel insight into the cumulative polyglutamine neurotoxicity, and supporting the usefulness of saccade peak velocity as a sensitive biomarker during the natural history of the disease, and as suitable outcome measure for future therapeutic trials, with high sensitivity in comparison to clinical scales. References: 1.Velazquez-Perez L, Seifried C, Santos-Falcon N, et al. Saccade velocity is controlled by polyglutamine size in spinocerebellar ataxia 2. Ann Neurol 2004;56:444-447. 2.MacAskill MR, Anderson TJ. Eye movements in neurodegenerative diseases. Curr Opin Neurol. 2016; 29(1):61-68.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/natural-history-of-saccadic-abnormalities-in-spinocerebellar-ataxia-2-implications-to-designing-future-clinical-trials/