GEN is a jerk nystagmus induced by moving the eyes into an eccentric position in the orbit, with fast phases beating in the direction of gaze. This manifests as drift of the eyes back from an eccentric to central position with decreasing-velocity slow-phase waveforms and corrective fast phases of nystagmus.
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.
Although there are different types of gaze-evoked nystagmus, the terms gaze-holding nystagmus (due to dysfunction of the neural integrator) and gaze-evoked nystagmus are often used interchangeably, although strictly speaking, this is imprecise. However, common practice is likely to dictate that gaze-evoked nystagmus continues to be used commonly as a synonym for pathological nystagmus due to integrator dysfunction (which is more accurately termed “gaze holding nystagmus”).
Video 1. Ocular examination for GEN
(vv)Examination of Gaze Holding Deficit Gaze Evoked Nystagmus.mp4(tt)
Pathogenesis
With GEN there is a normal pulse, but a poorly sustained degree of tonic innervation, the step: GEN is thus characterized by slow phases that show a declining exponential time course, and results from an unsustainable position command due to dysfunction (leakiness) of the neural integrator; that is, the medial vestibular nucleus, nucleus prepositus hypoglossi and the flocculus. For vertical GEN, this represents dysfunction of the INC (interstitial nucleus of Cajal).
Gaze-holding nystagmus may be horizontal, vertical, or both.
When it is purely horizontal, the nystagmus may be bilateral (present in both right gaze and left gaze) or unilateral (present with either rightward gaze or leftward gaze but not both). When it is purely vertical, the nystagmus may be present with either upward gaze, downward gaze, or both. Rarely downbeat nystagmus is elicited by upward gaze and has increasing velocity slow phases indicating instability of vertical gaze holding.
Types of GEN
1. Physiological end-point nystagmus, which occasionally can be difficult to distinguish from physiologic and pathologic gaze- evoked nystagmus.
2. Gaze-paretic nystagmus should only be applied in cases associated with paresis of gaze (from brainstem or hemispheric lesions or extraocular muscle weakness such as in myasthenia gravis).
3. Peripheral vestibular dysfunction
4. Central vestibular dysfunction
5. Central disturbances of gaze-holding mechanisms
Causes
Side effect of certain drugs, particularly anticonvulsants, hypnotics and tranquilizers
Diseases of the vestibulocerebellum or its brainstem connections in the MVN and nucleus prepositus hypoglossi. An ipsilateral lesion of the brainstem or cerebellum—typically stroke, demyelination, or tumour is presumed present.
Lesions of the flocculus.
Associated Features
With prolonged eccentric gaze, gaze-evoked nystagmus may dampen and even change direction. It is then called centripetal nystagmus and is often followed by rebound nystagmus when eyes returned to the primary position; slow phases are directed towards the prior position of eccentric gaze. Rebound nystagmus usually coexists with other cerebellar signs.
Video 2. GEN due to phenytoin toxicity
(vv)TARNGEN.mp4(tt)
From: Committee for the International Classification of Vestibular Disorders of the Barany Society.2.1.2.2.1.Downbeat Nystagmus. Retrieved from http://www.jvr-web.org/images/2.1.2.2.1.-Downbeat-nystagmus-A.m4v
Video 3. GEN due to a lesion of the flocculus.
(vv)NysfloccularoriginGEN.mp4(tt)
From: Clinical Examination of the Ocular Motor and Cerebellar Ocular Motor System. Strupp, M. https://www.youtube.com/watch?v=meXAjVoQdCI
Video 3. GEN due to a lesion of the fourth ventricle that compresses the brainstem and cerebellum
(vv)GEN.mp4(tt)
From: Choi SY, Choi YJ, Choi JH, Choi KD. Teaching Video Neuro: Macrosaccadic oscillations induced by horizontal head impulses. Neurology. 2017;89(9):e116. Retrieved from: https://n.neurology.org/content/89/9/e116