title: Spinocerebellar ataxia type 2: Measures of saccade changes improve power for clinical trials.
abstract: BACKGROUND
  Saccadic eye movement abnormalities are common in patients with spinocerebellar ataxia type 2, but it is unclear how these alterations progress over time. The aim of this study was to assess the progression of saccade involvement in spinocerebellar ataxia type 2 patients, identify its main determinants, and evaluate its usefulness as outcome measures in clinical trials.
  
  
  METHODS
  A prospective 5-year follow-up study was performed with 30 spinocerebellar ataxia type 2 patients and their matched healthy controls, who were evaluated a total of four times by clinical and electrooculographical assessments of horizontal saccades and by the scoring of ataxia.
  
  
  RESULTS
  Patients showed significant decreases in saccade peak velocity and saccade accuracy as well as 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 cytosine-adenine-guanine 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).
  
  
  CONCLUSIONS
  Electrooculographical measures of saccade changes are useful for the objective quantification of disease course in spinocerebellar ataxia type 2. The progression rate of saccade slowing is influenced by the 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 therapeutic trials.
authors: Department of Clinical Neurophysiology, Center for the Research and Rehabilitation of Hereditary Ataxias, Holguín, Cuba.
authors: Roberto
authors: R
authors: Rodríguez-Labrada
authors: Department of Clinical Neurophysiology, Center for the Research and Rehabilitation of Hereditary Ataxias, Holguín, Cuba.
authors: Luis
authors: L
authors: Velázquez-Pérez
authors: Section of Experimental Neurology, Department of Neurology, Goethe University Medical School, Frankfurt am Main, Germany.
authors: Georg
authors: G
authors: Auburger
authors: Department of Neurology & Stroke, and Hertie Institute for Clinical Brain Research, University Tübingen, Tübingen, Germany.
authors: Ulf
authors: U
authors: Ziemann
authors: Department of Clinical Neurophysiology, Center for the Research and Rehabilitation of Hereditary Ataxias, Holguín, Cuba.
authors: Nalia
authors: N
authors: Canales-Ochoa
authors: Department of Clinical Neurophysiology, Center for the Research and Rehabilitation of Hereditary Ataxias, Holguín, Cuba.
authors: Jacqueline
authors: J
authors: Medrano-Montero
authors: Department of Molecular Neurobiology, Center for the Research and Rehabilitation of Hereditary Ataxias, Holguín, Cuba.
authors: Yaimeé
authors: Y
authors: Vázquez-Mojena
authors: Department of Molecular Neurobiology, Center for the Research and Rehabilitation of Hereditary Ataxias, Holguín, Cuba.
authors: Yanetza
authors: Y
authors: González-Zaldivar
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002986:Clinical Trials as Topic / Q000379:methods / Q000592:standards; D018450:Disease Progression; D004585:Electrooculography / Q000379:methods* / Q000592:standards; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D015835:Ocular Motility Disorders / Q000209:etiology / Q000503:physiopathology*; D017063:Outcome Assessment, Health Care / Q000379:methods* / Q000592:standards; D012438:Saccades / Q000502:physiology*; D020754:Spinocerebellar Ataxias / Q000150:complications / Q000503:physiopathology*; D055815:Young Adult
keywords: SCA2; clinical trials; longitudinal study; saccade slowing; saccadic eye movements; spinocerebellar ataxias