title: Eye movement abnormalities in spinocerebellar ataxia type 17 (SCA17).
abstract: BACKGROUND
  Spinocerebellar ataxia type 17 (SCA17) is associated with an expansion of CAG/CAA trinucleotide repeats in the gene encoding the TATA-binding protein. In this quantitative characterization of eye movements in SCA17 mutation carriers, we investigated whether eye movement abnormalities originate from multiple lesion sites as suggested by their phenotypic heterogeneity.
  
  
  METHODS
  Eye movements (saccades, smooth pursuit) of 15 SCA17 mutation carriers (mean age 36.9 years, range 20 to 54 years; mean disease duration 7.3 years, range 0 to 20 years; 2 clinically unaffected, 13 affected) were compared with 15 age-matched control subjects using the video-based two-dimensional EYELINK II system.
  
  
  RESULTS
  Smooth pursuit initiation (step-ramp paradigm) and maintenance were strongly impaired, i.e., pursuit latency was increased and acceleration decreased, whereas latency and position error of the first catch-up saccade were normal. Visually guided saccades were hypometric but had normal velocities. Gaze-evoked nystagmus was found in one-third of the mutation carriers, including downbeat and rebound nystagmus. There was a pathologic increase in error rates of antisaccades (52%) and memory-guided saccades (42%). Oculomotor disorders were not correlated with repeat length. Smooth pursuit impairment and saccadic disorders increased with disease duration.
  
  
  CONCLUSIONS
  Several oculomotor deficits of spinocerebellar ataxia type 17 (SCA17) mutation carriers are compatible with cerebellar degeneration. This is consistent with histopathologic and imaging (morphometric) data. In contrast, increased error rates in antisaccades and memory-guided saccades point to a deficient frontal inhibition of reflexive movements, which is probably best explained by cortical dysfunction and may be related to other phenotypic SCA17 signs, e.g., dementia and parkinsonism.
authors.affiliation: Department of Neurology, University of Luebeck, Luebeck, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Hübner
authors.forename: A
authors.initials: A
authors.lastname: Sprenger
authors.forename: C
authors.initials: C
authors.lastname: Klein
authors.forename: J
authors.initials: J
authors.lastname: Hagenah
authors.forename: H
authors.initials: H
authors.lastname: Rambold
authors.forename: C
authors.initials: C
authors.lastname: Zühlke
authors.forename: D
authors.initials: D
authors.lastname: Kömpf
authors.forename: A
authors.initials: A
authors.lastname: Rolfs
authors.forename: H
authors.initials: H
authors.lastname: Kimmig
authors.forename: C
authors.initials: C
authors.lastname: Helmchen
mesh_terms: D000328:Adult; D001921:Brain / Q000473:pathology / Q000503:physiopathology*; D002531:Cerebellum / Q000473:pathology / Q000503:physiopathology; D004252:DNA Mutational Analysis; D005260:Female; D005625:Frontal Lobe / Q000473:pathology / Q000503:physiopathology; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009434:Neural Pathways / Q000473:pathology / Q000503:physiopathology; D015835:Ocular Motility Disorders / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D012438:Saccades / Q000502:physiology; D020754:Spinocerebellar Ataxias / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D035181:TATA-Box Binding Protein / Q000235:genetics*
chemical_list: D035181:TATA-Box Binding Protein; C509817:TBP protein, human