Oculomotor deficits in spinocerebellar ataxia type 3: Potential biomarkers of preclinical detection and disease progression.

OBJECTIVE

To detect specific oculomotor deficits in preclinical stage of spinocerebellar ataxia type 3 (SCA3) and evaluate whether these abnormalities prove useful as potential biomarkers of disease progression.

METHODS

A Chinese cohort of 56 patients with SCA3, including 12 preclinical carriers of SCA3 (pre-SCA3) and 44 manifest SCA3, and 26 healthy control individuals were recruited. We performed a detailed investigation on central oculomotor performance including fixation, gaze, smooth pursuit, prosaccade, and antisaccade using video-oculography.

RESULTS

Common oculomotor features of pre-SCA3 included square-wave jerk during central fixation and gaze holding, impaired vertical smooth pursuit, slow upward saccade, and increased antisaccade error rate. In our SCA3 cohort, all oculomotor parameters were correlated with the score of the Scale for the Assessment and Rating of Ataxia, whilst some of them were correlated with disease duration.

CONCLUSIONS

This study showed that a series of neuropathological changes reflected by oculomotor abnormalities appeared preferentially in preclinical stage of SCA3. Accordingly, objective oculomotor preclinical signs may be useful to detect the optimum time-point for therapeutic interventions in future clinical trials of SCA3. Larger and longitudinal data are warranted to confirm our results.