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.
DESIGN: Physiological techniques were used to record and analyze eye movements and postural sway. PATIENTS: 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.