Vestibular-Ocular System (Vestibular-Ocular Reflex)
The VOR holds foveal alignment on a target of interest during brief, high-frequency head movements by generating ocular rotations of equal speed, and in the opposite direction, as that of the head movements. VOR responses are driven by the labyrinth, which is composed of 3 semicircular canals and the otoliths (the utricle and saccule). The labyrinth contains hair cells with cilia that project into the endolymph fluid. Head movement causes endolymph flow that deflects cilia on the hair cells, subsequently altering the neurologic activity of CN VIII. The semicircular canals respond to head rotation, and the otoliths respond to linear head movements and static head tilt. Neural activity (excitatory and inhibitory) from these structures passes along the vestibular nerves to synapses in the CN VIII nuclei in the medulla of the brainstem; from there, the activity projects to the ocular motor nuclei (ie, the VOR pathway; see Chapter 1). CN VIII nuclei have many interconnections with the cerebellum that “fine-tune” the VOR.
Each semicircular canal responds to head movements and governs ocular rotations within the same plane as the canal. In addition, each semicircular canal responds in opposite ways to head movements in each direction within the plane of the canal. Thus, the right horizontal semicircular canal stimulates right CN VIII discharge in response to rightward head rotation and inhibits right CN VIII discharge in response to leftward head rotation. Conversely, the left horizontal semicircular canal excites the left CN VIII in response to leftward head rotation and inhibits the left CN VIII in response to rightward head rotation. This arrangement results in a “push–pull” relationship between the paired canals in which stimulation from 1 canal occurs with inhibition from the contralateral, paired canal.
Stimulation from the horizontal semicircular canal projects via the CN VIII nucleus to the contralateral CN VI nucleus, resulting in horizontal ocular rotations away from the side of the canal. For example, stimulating the right horizontal semicircular canal generates left gaze. Together, the horizontal canals generate horizontal ocular rotations that are equal in speed and opposite in direction to horizontal head rotation. For example, rightward head rotation stimulates the right horizontal semicircular canal (and inhibits the left horizontal semicircular canal) to generate leftward ocular rotations.
The anterior semicircular canals stimulate upgaze (in response to downward head rotation), and the posterior canals stimulate downgaze (in response to upward head rotation). The anterior and posterior canals also stimulate contralateral torsion in response to dynamic ipsilateral head tilt.
Sustained head rotation stimulates the VOR to generate slow-phase ocular movements that are opposite the direction of head rotation (to maintain fixation); these alternate with fast-phase, reflexive, refixation saccades in the direction of head rotation (VOR nystagmus). The VOR response to sustained head rotation attenuates fairly quickly as the cilia on the hair cells resume their normal position. However, a “velocity storage” mechanism prolongs the VOR for several seconds during sustained head movements. This velocity storage mechanism is generated by interconnections within the CN VIII nuclei (the vestibular commissure) and is fine-tuned and stabilized by connections with the cerebellum.
The otoliths (saccule and utricle) respond to linear head movement and static head tilt. Head tilt stimulates a response that improves ocular orientation with the horizontal plane. Thus, rightward head tilt stimulates the right otolith to generate compensatory elevation and intorsion of the right eye and depression and extorsion of the left eye. Conversely, leftward head tilt stimulates the left otolith to generate compensatory elevation and intorsion of the left eye and depression and extorsion of the right eye.
Examination can readily elicit evidence of VOR dysfunction. Spontaneous nystagmus may be a sign of imbalanced vestibular input, resulting in a slow-phase gaze deviation that disrupts fixation, followed by a corrective saccade. Nystagmus can be detected by observation of the eyes as the patient fixates on a distant target with the head stationary. Subtle small-amplitude nystagmus can be detected by viewing the fundus with a direct ophthalmoscope while looking for repetitive shifts in the position of the optic nerve head. Note that the optic nerve head is behind the center of ocular rotation and will therefore beat in a direction opposite to that of the nystagmus. This test is first performed while the fellow eye is allowed to fixate on a target. Next, the effect of removing visual fixation (achieved by covering the fixating eye) is assessed. Fixation suppresses nystagmus from peripheral vestibular disorders; thus, the onset of nystagmus after removal of visual fixation suggests the presence of an imbalance of the peripheral vestibular system. In contrast, nystagmus from central vestibular disorders is not altered by fixation and will therefore be observed with or without fixation (see Chapter 9).
The VOR gain (ie, the ratio of the amplitude of eye rotation to the amplitude of head rotation) can be assessed clinically with the head thrust maneuver, which requires the clinician to turn the patient’s head briskly while the patient fixates on a target. Normally, if the head is rotated 10°, the eyes will rotate exactly 10° in the opposite direction, with equal speed, to maintain foveation of a stationary target. Any imbalance in the VOR gain results in the eyes being dragged off target at the end of the head thrust, followed by a refixation saccade to recapture the target. The horizontal semicircular canals are evaluated by horizontal head rotation. When the head is rotated toward the side of the lesion, a defective response is observed. For example, rightward head rotation should stimulate the right horizontal semicircular canal to generate leftward ocular rotations of equal speed and amplitude. If a lesion is present in the right horizontal semicircular canal pathway, the eyes will be dragged off target, followed by a leftward, compensatory, refixation saccade. The anterior and posterior semicircular canals can be assessed by vertical head rotations.
VOR gain may also be tested by measuring visual acuity during head rotations (dynamic visual acuity). Relatively small horizontal or vertical head rotations at approximately 2 Hz are performed while the patient reads the Snellen chart. In a patient with normal VOR gain, visual acuity will decrease by 1 or 2 lines at most. Abnormal VOR gain will produce a mismatch between the amplitude of the eye and head movements, causing the intended target to drift off the fovea, resulting in a decrease in visual acuity by several lines (typically 4 or more).
Eye movement abnormalities can develop from either peripheral or central disruptions of vestibular activity, although peripheral end-organ disease of the semicircular canals is by far the most common cause of such abnormalities. Patients with vestibular disease often have nystagmus and abnormal VOR gain (see Chapter 9).
Otolith dysfunction may produce skew deviation or an ocular tilt reaction. Skew deviation is a vertical misalignment of the eyes caused by asymmetrical otolithic input to the ocular motor nuclei. The vertical misalignment, which may be comitant or incomitant, may simulate a CN IV palsy, including a positive head tilt test. However, skew deviation typically occurs with intorsion of the hypertropic eye. In contrast, CN IV palsy causes extorsion of the hypertropic eye. Additionally, the vertical deviation in skew deviation typically improves when the patient lies down, whereas it does not change in CN IV palsy. An alternating skew deviation manifests as hypertropia of the abducting eye (ie, right hypertropia on right gaze and left hypertropia on left gaze).
The ocular tilt reaction, which occurs with otolithic imbalance, consists of a head tilt, skew deviation, and cyclotorsional rotation of the eyes (Fig 8-1). As described earlier, normally, the otoliths respond to head tilt to improve ocular orientation with the horizontal plane (eg, a right head tilt stimulates the right otolith, resulting in elevation and intorsion of the right eye, and depression and extorsion of the left eye). However, a lesion that decreases innervation from the left otolith (resulting in a pathologic relative increase in innervation from the right otolith) will drive the head tilt and generate a left head tilt, elevation and intorsion of the right eye, and depression and extorsion of the left eye (left ocular tilt reaction). The subjective visual vertical may be tilted in the direction of the ocular rotation, although the patient may not recognize that such a shift has occurred.
Figure 8-1 Right ocular tilt reaction. To achieve the illusion of normal upright orientation (1), an ocular tilt reaction (2) compensates for the apparent tilt of the environment. With the ocular tilt reaction, the upper poles of each eye rotate toward the lower ear.
(Modified with permission from Kline LB, Bajandas FJ. Neuro-Ophthalmology Review Manual. 6th ed. Thorofare, NJ: Slack; 2008:71. Modified from Brandt T, Dieterich M. Pathological eye-hand coordination in roll: tonic ocular tilt reaction in mesencephalic and medullary lesions. Brain. 1987;110(Pt 3):649–666.)
Skew deviation and the ocular tilt reaction are caused by peripheral or central nervous system (CNS) lesions. A peripheral lesion will generally be ipsilateral to the hypotropic eye (eg, a left otolith lesion is associated with left hypotropic skew deviation or left ocular tilt reaction). However, otolithic innervation crosses within the CNS and projects to multiple ocular motor nuclei, the interstitial nucleus of Cajal, and the cerebellum. Thus, skew deviation and the ocular tilt reaction do not localize dysfunction to a specific region of the CNS and may be caused by lesions anywhere in the brainstem or cerebellum (eg, the posterior fossa) that result in asymmetric otolithic input to the ocular motor nuclei.
Vestibular imbalance is common with lesions of the caudal brainstem (lower pons and medulla) because of disruption to the CN VIII nuclei or their interconnections. One of the better-known stroke syndromes involving this area is the lateral medullary syndrome (or Wallenberg syndrome). In general, damage to a lateral region of the brainstem disrupts the sensory pathways; therefore, Wallenberg syndrome is a type of “stroke without paralysis” (see Chapter 2, Fig 2-6). Patients may present with the following signs and symptoms:
ipsilateral loss of facial pain and temperature sensation (involvement of the descending tract of CN V)
contralateral loss of hemibody pain and temperature sensation (involvement of the lateral spinothalamic tract)
ipsilateral cerebellar ataxia (damage to spinocerebellar tracts)
ipsilateral first-order Horner syndrome
ipsilateral ocular tilt reaction (head tilt toward the side of the lesion)
In addition, patients may have dysarthria, dysphagia, vertigo, or persistent hiccups; there is no extremity weakness.
Although the lateral medulla is in the distribution of the posterior inferior cerebellar artery (PICA), Wallenberg syndrome usually results from occlusion of the more proximal vertebral artery. Consequently, patients may experience lateropulsion, the sensation of being pulled toward the side of the lesion, which results from damage to the CN VIII nuclei. Patients may also manifest ocular lateropulsion; this effect can be tested by examination of horizontal pursuit and saccadic movements, which will reveal a bias that produces hypermetric movements toward the side of the lesion and hypometric movements away from the side of the lesion. Vertical saccades may follow an elliptical path as the eyes deviate toward the side of the lesion during the vertical movement. Finally, this directional bias also can be observed by noting that the eyes turn toward the side of the lesion after visual fixation is removed for a few seconds.
Brodsky MC, Donahue SP, Vaphiades M, Brandt T. Skew deviation revisited. Surv Ophthalmol. 2006;51(2):105–128.
Donahue SP, Lavin PJ, Hamed LM. Tonic ocular tilt reaction simulating a superior oblique palsy: diagnostic confusion with the 3-step test. Arch Ophthalmol. 1999;117(3):347–352.
Wong AM, Colpa L, Chandrakumar M. Ability of an upright-supine test to differentiate skew deviation from other vertical strabismus causes. Arch Ophthalmol. 2011;129(12):1570–1575.
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.