Gabapentin and memantine increases randomness of oscillatory waveform in ocular palatal tremor

Syndrome of oculopalatal tremor (OPT) causes pendular nystagmus of the eyes and its disabling consequence on the visual system. Classic pharmacotherapeutic studies revealed reduction in the eye velocity of the oscillatory waveforms. Subjective improvement in vision, however, remains out of proportionately low. Elegant models depicting quasi-sinusoidal coarse oscillations of the eyes highlighted two distinct oscillators; one at the inferior olive causing primary 2 Hz oscillations, while the second, independent oscillator, at the cerebellum adding the randomness to the waveform. Here we examined whether pharmacotherapy affects the randomness of the oscillatory waveform. Horizontal, vertical, and torsional angular eye positions were measured independently from both eyes as six subjects with OPT directed gaze toward a straight-ahead target. The measurements were performed before administration of alpha-2-delta calcium channel blocker (gabapentin) or NMDA receptor antagonist (memantine) and after the subjects were treated with each of these drugs for at least 8 days. Amplitude and velocity of eye oscillations were reduced by gabapentin and memantine, but there was an increase in the waveform randomness. We found that the increase in randomness was proportionate to the amount of reduction in the waveform velocity or amplitude. Hierarchical clustering revealed distinct patterns of oscillatory waveforms, with each subject belonging to a specific cluster group. The pharmacotherapy changed the waveform clustering pattern of the waveform in each subject. We conclude that in addition to incomplete resolution of the oscillation intensity, increased randomness could be one of the reasons why there is not enough clinical difference in the patients’ visual quality.