title: Quantitative assessment of the evolution of cerebellar signs in spinocerebellar ataxias.
abstract: BACKGROUND
  Responsive ataxia rating scales are essential for determining outcome measures in clinical trials.
  
  
  METHODS
  We evaluated the responsiveness over time of the composite cerebellar functional severity score, a quantitative score measuring cerebellar ataxia in 133 patients with autosomal dominant cerebellar ataxias (ADCA), which were prospectively evaluated at inclusion and after one-year of follow-up. A more responsive tool was developed, the Cerebellar Functional Severity score writing, incorporating the writing test at dominant hand to the Cerebellar Functional Severity score.
  
  
  RESULTS
  Within the one-year follow-up period, the Cerebellar Functional Severity score and its writing version increased significantly and the Scale for the Assessment and Rating of Ataxia decreased significantly reflecting increased severity of the cerebellar symptoms. The Cerebellar Functional Severity score writing responsiveness was best in genotypes SCA1, 2, and 3 compared with the other genotypes (effect size = 0.196, standardized response mean (SRM) = 0.624 versus effect size = -0.051, SRM = -0.150). The Cerebellar Functional Severity score writing used as an outcome measure would require only 163 SCA1, 2, or 3 patients per group in a two-arm interventional trial for a 50% reduction in progression and 80% of power.
  
  
  CONCLUSIONS
  Our study demonstrates that the Cerebellar Functional Severity score and Cerebellar Functional Severity score writing are responsive quantitative scores for evaluating sensitivity to change in ADCA patients and can be used as outcome measures in clinical trials, especially when targeting genotypes SCA1, 2 and 3.
authors.affiliation: Department of Biostatistics and Medical Informatics and Pitié-Salpêtrière Charles-Foix Clinical Research Unit, AP-HP, Paris, France.
authors.forename: Ellis
authors.initials: E
authors.lastname: Chan
authors.forename: Perrine
authors.initials: P
authors.lastname: Charles
authors.forename: Pascale
authors.initials: P
authors.lastname: Ribai
authors.forename: Cyril
authors.initials: C
authors.lastname: Goizet
authors.forename: Cecilia
authors.initials: C
authors.lastname: Marelli
authors.forename: Carlo-Maria
authors.initials: CM
authors.lastname: Vincitorio
authors.forename: Alice
authors.initials: A
authors.lastname: Le Bayon
authors.forename: Lucie
authors.initials: L
authors.lastname: Guyant-Maréchal
authors.forename: Nadia
authors.initials: N
authors.lastname: Vandenberghe
authors.forename: Mathieu
authors.initials: M
authors.lastname: Anheim
authors.forename: David
authors.initials: D
authors.lastname: Devos
authors.forename: Leorah
authors.initials: L
authors.lastname: Freeman
authors.forename: Isabelle
authors.initials: I
authors.lastname: Le Ber
authors.forename: Karine
authors.initials: K
authors.lastname: N'Guyen
authors.forename: Maya
authors.initials: M
authors.lastname: Tchikviladzé
authors.forename: Pierre
authors.initials: P
authors.lastname: Labauge
authors.forename: Didier
authors.initials: D
authors.lastname: Hannequin
authors.forename: Alexis
authors.initials: A
authors.lastname: Brice
authors.forename: Alexandra
authors.initials: A
authors.lastname: Durr
authors.forename: Sophie Tezenas
authors.initials: ST
authors.lastname: du Montcel
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D002531:Cerebellum / Q000473:pathology / Q000503:physiopathology*; D004185:Disability Evaluation; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D018401:Sample Size; D012720:Severity of Illness Index; D020754:Spinocerebellar Ataxias / Q000175:diagnosis* / Q000503:physiopathology*; D013223:Statistics as Topic; D055815:Young Adult