Prolonged Asymmetric Smooth-Pursuit Stimulation Leads to Downbeat Nystagmus in Healthy Human Subjects

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