Prolonged asymmetric smooth-pursuit stimulation leads to downbeat nystagmus in healthy human subjects.

Objective: Downbeat nystagmus (DBN) is a typical ocular motor sign in patients with lesions of the vestibulocerebellum. A vertical vestibular tone asymmetry, an upward shift of the eyes' null position for vertical gaze holding, or an imbalance of vertical smooth-pursuit signals have been proposed as mechanisms of DBN. The purpose of this study was to elaborate a possible link between an imbalance in the vertical smooth-pursuit system and DBN by relying on a healthy human model.

Methods: Healthy subjects (n=6) were exposed to continuous asymmetric smooth-pursuit stimulation over 20 minutes.

Results: Prolonged asymmetric smooth-pursuit stimulation induced a drift lasting >5 minutes in the direction of the prior pursuit. Upward drift was faster than downward drift and showed eye-position dependence in accordance with Alexander's law, but no increase of drift velocity with lateral gaze. Upward drift violated Listing's law in three of four subjects tested.

Conclusions: An experimentally induced vertical smooth-pursuit imbalance leads to DBN in healthy human subjects. Accordingly, because in patients with cerebellar disease upward smooth-pursuit eye movements are typically better preserved than downward, the resultant sustained imbalance of vertical smooth-pursuit input may play a major role in the generation of DBN.