Effect of 3,4-Diaminopyridine on the Gravity Dependence of Ocular Drift in Downbeat Nystagmus

Background: The pathomechanism of downbeat nystagmus (DBN) remains controversial but each mechanism has to account for (i) its gaze evoked vertical centripetal drift which increases with vertical gaze eccentricity, and (ii) the vertical bias component of the upward slow phase velocity on gaze straight ahead. The vertical velocity bias has a gravity-dependent component which leads to maximal drift velocity when patients lie in a prone position and minimal in a supine position. Recently, the potassium channel blocker 3,4-diaminopyridine (3,4-DAP) has been shown to be effective in DBN of patients with the head upright. Purpose: To investigate the effect of 3,4-diaminopyridine on gaze- and gravity-dependent mechanisms of DBN. Material and Methods: Eye movements were recorded in one patient with idiopathic DBN with the video-based EYELINK II system. Fixation targets were head-fixed LEDs, which were presented in front of the patient at a fixed distance (60cm) in gaze straight ahead and + 100 up and down. Horizontal targets were presented at 400. The pitch head position was monitored and adjusted by an inclinometer. Results: There was a strong gravity-dependent velocity bias component which was maximal in the prone position and turned into upbeat nystagmus (UBN) in the supine position on gaze straight ahead. Following 3,4-DAP ingestion, the slow phase velocity of DBN was hardly affected in gaze straight ahead or lateral gaze but was strongly reduced in the head tilted forward position, i.e., in the prone position by >50%, whereas upbeat nystagmus in the supine position was not affected. Conclusions: This effect cannot simply be explained by a shift of the velocity bias in a downward direction but rather implicates that 3,4-DAP may particularly influence the gravity-dependent component of DBN which may be the leading clinical feature in DBN.