title: Gait impairment precedes clinical symptoms in spinocerebellar ataxia type 6.
abstract: BACKGROUND
  Spinocerebellar ataxia type 6 (SCA6) is an inherited ataxia with no established treatment. Gait ataxia is a prominent feature causing substantial disability. Understanding the evolution of the gait disturbance is a key step in developing treatment strategies.
  
  
  METHODS
  We studied 9 gait variables in 24 SCA6 (6 presymptomatic; 18 symptomatic) and 24 controls and correlated gait with clinical severity (presymptomatic and symptomatic).
  
  
  RESULTS
  Discrete gait characteristics precede symptoms in SCA6 with significantly increased variability of step width and step time, whereas a more global gait deficit was evident in symptomatic individuals. Gait characteristics discriminated between presymptomatic and symptomatic individuals and were selectively associated with disease severity.
  
  
  CONCLUSIONS
  This is the largest study to include a detailed characterization of gait in SCA6, including presymptomatic subjects, allowing changes across the disease spectrum to be compared. Selective gait disturbance is already present in SCA6 before clinical symptoms appear and gait characteristics are also sensitive to disease progression. Early gait disturbance likely reflects primary pathology distinct from secondary changes. These findings open the opportunity for early evaluation and sensitive measures of therapeutic efficacy using instrumented gait analysis which may have broader relevance for all degenerative ataxias.
authors.affiliation: Institute for Ageing and Health, Clinical Ageing Research Unit, Newcastle University, Newcastle upon Tyne, United Kingdom.
authors.forename: Lynn
authors.initials: L
authors.lastname: Rochester
authors.forename: Brook
authors.initials: B
authors.lastname: Galna
authors.forename: Sue
authors.initials: S
authors.lastname: Lord
authors.forename: Dadirayi
authors.initials: D
authors.lastname: Mhiripiri
authors.forename: Gail
authors.initials: G
authors.lastname: Eglon
authors.forename: Patrick F
authors.initials: PF
authors.lastname: Chinnery
mesh_terms: D000328:Adult; D000368:Aged; D015220:Calcium Channels / Q000235:genetics; D018450:Disease Progression; D005260:Female; D020233:Gait Disorders, Neurologic / Q000150:complications*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D020754:Spinocerebellar Ataxias / Q000150:complications* / Q000235:genetics; D020864:Calcium Channels, N-Type
chemical_list: D015220:Calcium Channels; C105656:CACNA1A protein, human; D020864:Calcium Channels, N-Type
keywords: SCA6; ataxia; gait; presymptomatic; symptomatic