Impaired eye movements in presymptomatic spinocerebellar ataxia type 6.
BACKGROUND
Early detection of impaired neurological function in neurodegenerative diseases may aid in understanding disease pathogenesis and timing of therapeutic trials.


OBJECTIVE
To identify early abnormalities of ocular motor function in individuals who have the spinocerebellar ataxia type 6 (SCA6) gene (CACNA1A) but no clinical symptoms.


METHODS
Physiological techniques were used to record and analyze eye movements and postural sway.


METHODS
Four presymptomatic and 5 ataxic patients with SCA6, genetically identified, and 10 healthy controls.


RESULTS
Presymptomatic individuals had normal postural sway but definite ocular motor abnormalities. Two had a low-amplitude horizontal gaze-evoked nystagmus, 1 of whom had a significantly decreased eye velocity for upward saccades and an abnormal frequency of square-wave jerks. Another had abnormal square-wave jerks and a fourth had a reduced gain for pursuit tracking. Not all of the presymptomatic patients had the same findings, but a multivariate analysis discriminated the presymptomatic patients, as a group, from healthy controls and the ataxic patients.


CONCLUSIONS
Among the earliest functional deficits in SCA6 are eye movement abnormalities, including impaired saccade velocity, saccade metrics, and pursuit gain. This suggests that early functional impairments are caused by cellular dysfunction and/or loss in the posterior cerebellar vermis and flocculus. These findings might help to determine the timing of a treatment and to define variables that could be used as outcome measures for the efficacy of therapeutic trials.
Christova
Peka
P
Department of Neuroscience, University of Minnesota, Minneapolis 55455, USA.
Anderson
John H
JH
Gomez
Christopher M
CM
D000328:Adult; D015220:Calcium Channels / Q000235:genetics; D016022:Case-Control Studies; D002531:Cerebellum / Q000503:physiopathology; D042241:Early Diagnosis; D005260:Female; D006801:Humans; D008297:Male; D009460:Neurologic Examination; D015835:Ocular Motility Disorders / Q000175:diagnosis* / Q000235:genetics / Q000503:physiopathology; D004856:Postural Balance / Q000502:physiology; D011698:Pursuit, Smooth / Q000235:genetics / Q000502:physiology; D012438:Saccades / Q000235:genetics / Q000502:physiology; D020754:Spinocerebellar Ataxias / Q000175:diagnosis* / Q000235:genetics; D020864:Calcium Channels, N-Type
D015220:Calcium Channels; C105656:CACNA1A protein, human; D020864:Calcium Channels, N-Type