Gaze-evoked nystagmus develops because of an inability to maintain fixation in eccentric gaze. The eyes drift back to the midline as a result of the elastic properties of the orbit, and a corrective saccade is generated to reposition the eyes on the eccentric target. Therefore, the fast phase is always in the direction of gaze. The amplitude of the nystagmus increases as the eyes are moved in the direction of the fast phase. This pattern is in accordance with Alexander’s law, which states that nystagmus increases in intensity (amplitude and frequency) as the eyes are moved in the direction of the fast phase.
Gaze-evoked nystagmus is most commonly caused by dysfunction of the neural integrator (see Chapters 1 and 8). For horizontal gaze, the neural integrator includes the nucleus prepositus hypoglossi and the medial vestibular nuclei. For vertical gaze, the interstitial nucleus of Cajal serves as the neural integrator. The cerebellum also participates in neural integration of both horizontal and vertical eye movements.
When eccentric gaze is initiated, the neural integrator receives a velocity signal (the pulse) from the appropriate gaze center and, through the mathematical process of integration, generates tonic innervation (a step signal) to maintain the eccentric position of the eyes after the ocular movements have been completed (see Chapter 8, Fig 8-2). Thus, the neural integrator ensures a level of neural activity adequate to maintain the eyes in an eccentric position of gaze against the elastic forces of the orbit. If the neural integrator fails to function properly (ie, becomes “leaky”), then the tonic innervation (step signal) that holds the eyes in eccentric gaze is deficient. Therefore, after completion of eccentric gaze, the eyes slowly drift off the target back to the central position, followed by a corrective saccade toward the target—hence the term gaze-evoked nystagmus.
Pathologic gaze-evoked nystagmus is caused by dysfunction of the structures in the brainstem and cerebellum that participate in neural integration. A few beats of symmetric, low-frequency, small-amplitude jerk nystagmus at the extremes of far horizontal gaze without other ocular motility dysfunction (eg, rebound nystagmus or saccadic dysmetria) constitute physiologic endpoint nystagmus and are not clinically significant. However, sustained, large-amplitude, or asymmetric gaze-evoked nystagmus is pathologic and should prompt further evaluation. The 2 most common etiologies are (1) toxic effects from drugs and medications (eg, alcohol, sedatives, anticonvulsants, and antidepressants) and (2) cerebellar disease. Whenever gaze-evoked nystagmus is asymmetric, an ipsilateral lesion of the brainstem or cerebellum—typically stroke, demyelination, or tumor—is presumably present. Such a finding should prompt appropriate patient evaluation, including targeted neuroimaging. End-organ disease, such as extraocular myopathies and myasthenia gravis, can also cause gaze-evoked nystagmus, with a pattern similar to that observed with lesions of the central nervous system.
In some patients with gaze-evoked nystagmus, prolonged eccentric gaze (>30 seconds) reduces the amplitude of the nystagmus. However, when the patient resumes central gaze position, a jerk nystagmus develops in the opposite direction of the initial gaze-evoked nystagmus, a condition referred to as rebound nystagmus. Prolonged eccentric viewing likely induces brainstem/cerebellar compensatory mechanisms that gradually increase tonic innervation toward eccentric gaze, thereby reducing the gaze-evoked nystagmus. When the patient resumes central gaze, residual tonic innervation continues to drive the eyes toward the prior eccentric gaze position, followed by a corrective saccade in the opposite direction (rebound nystagmus). For example, a patient with gaze-evoked nystagmus may have a gradual reduction of the amplitude of a rightward-beating nystagmus with prolonged right gaze because brainstem/cerebellar compensatory mechanisms gradually increase tonic right-gaze innervation. However, upon resuming central gaze, the residual tonic right-gaze innervation continues, inducing a slow-phase ocular rotation toward the right, followed by a corrective, leftward-beating saccade (ie, rightward-beating gaze-evoked nystagmus in right gaze followed by leftward-beating rebound nystagmus upon resuming central gaze). Gaze-evoked nystagmus accompanied by rebound nystagmus is often a manifestation of cerebellar disease.
Excerpted from BCSC 2020-2021 series: Section 5 - Neuro-Ophthalmology. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.