Optokinetic Nystagmus

This type of nystagmus may be elicited in all normal individuals, most easily by means of a rotating drum with alternating black and white lines but in fact by any repetitive targets in the visual field such as repetitive telephone poles as seen from a window of a fast-moving vehicle. The slow component follows the object and the fast component moves rapidly in the opposite direction to fixate on each succeeding object. A unilateral or asymmetric horizontal response usually indicates a deep parietal lobe lesion, especially a tumor. It occurs as a result of a deficit in the slow (pursuit) phase. Anterior cerebral (ie, frontal lobe) lesions may inhibit this response only temporarily when an acute saccadic gaze palsy is present, which suggests the presence of a compensatory mechanism that is much greater than for lesions situated farther posteriorly. Asymmetry of response in the vertical plane suggests a brainstem lesion. Since it is an involuntary response, this test is especially useful in detecting hysteria or malingering. A large mirror filling the patient's central field at near can be rotated from side to side and will induce an optokinetic nystagmus if vision is present.

Stimulation of Semicircular Canals

The three semicircular canals of each inner ear sense movements of the head in space, being primarily sensitive to acceleration. The neural output of the vestibular system, after processing within the vestibular and related brainstem nuclei, is a velocity signal. This is transmitted, principally via the medial longitudinal fasciculus on each side of the brainstem, to the ocular motor nuclei to produce the necessary compensatory eye movements (vestibulo- ocular responses) for maintaining a stable position of the eyes in space and hence optimal vision. Vestibular signals also pass to the cerebellum and cerebral cortex.

Stimulation of the semicircular canals results in a compensatory eye movement. In the unconscious subject with an intact brainstem, this leads to a tonic deviation of the eyes, whereas in the conscious subject a superimposed corrective fast phase movement, returning the eyes back toward the straight-ahead position, results in a jerk nystagmus. These tests are useful methods of investigating vestibular function in conscious subjects and, in the case of caloric stimulation, brainstem function in comatose patients.

A. Rotatory Physiologic Nystagmus (Bárány Rotating Chair):

When the head is tilted 30 degrees forward, the horizontal semicircular canals lie horizontally in space. Rotation, such as in a Bárány, then leads to a horizontal jerk nystagmus with the compensatory slow phase eye movement opposite to the direction of turning and the corrective fast phase in the direction of turning. Owing to impersistence of the vestibular signal during continued rotation, the nystagmus abates. Once the rotation stops, there is a vestibular tone in the opposite direction, which results in a jerk nystagmus with the fast phase away from the original direction of turning (postrotatory nystagmus). Since the subject is stationary, postrotatory nystagmus is often easier to analyze than the nystagmus during rotation

B. Caloric Stimulation:

With the head tilted 60 degrees backward, the horizontal semicircular canals lie vertically in space. Water irrigation of the auditory canal then generates convection currents predominantly within the horizontal rather than the vertical semicircular canals. Cold water irrigation induces a predominantly horizontal jerk nystagmus with a fast phase opposite to the side of irrigation, and warm water irrigation induces a similar jerk nystagmus with a fast phase toward the side of irrigation. (The mnemonic device is "COWS": cold-opposite, warm-same.) Caloric nystagmus is made more obvious by the patient wearing Frenzel's spectacles, which eliminate patient fixation and provide a magnified view for the examiner. It is important to verify that the tympanic membrane is intact before performing irrigation of the external auditory canal.

Voluntary Nystagmus

About 5% of normal individuals can generate short bursts of ocular oscillation that resemble small-amplitude, fast, horizontal pendular nystagmus. Eye movement recordings show the movements to be rapidly alternating saccades. Recognition of the entity is important to avoid unnecessary investigation.

PATHOLOGIC NYSTAGMUS

Congenital Nystagmus

Congenital nystagmus is nystagmus present within 6 months after birth. Ocular instability is usual at birth, due to poor visual fixation, but this abates during the first few weeks of life. The presence of spontaneous nystagmus is always pathologic.

Congenital impairment of vision or visual deprivation due to lesions in any part of the eye or optic nerve can result in nystagmus at birth or soon thereafter. Causes include corneal opacity, cataract, albinism, achromatopsia, bilateral macular disease, aniridia, and optic atrophy. By definition, congenital idiopathic motor nystagmus has no associated underlying sensory abnormality, though visual performance is limited by the ocular instability. Typically it is not present at birth but becomes apparent between 3 and 6 months of age.

At one time it was thought that congenital pendular nystagmus was indicative of an underlying sensory abnormality whereas congenital jerk nystagmus was not. Eye movement recordings have shown this not to be true, both pendular and jerk waveforms being seen whether there is a sensory abnormality or not. Indeed, in many cases a mixed pattern of alternating pendular and jerk waveforms is seen. Congenital nystagmus, particularly the idiopathic motor type with its potential for better visual fixation, generally undergoes a progressive change in its waveform during early childhood. There is development of periods of relative ocular stability, ie, relatively slow eye velocity, known as foveation periods since they are thought to be an adaptive response to maximize the potential for fixation and hence to improve visual acuity. In addition, congenital nystagmus with a jerk nystagmus has a characteristic waveform in which the slow phases have an exponentially increasing velocity. This is known as CN type waveform, and with very few exceptions its presence signifies that the nystagmus has been present since early childhood. This can be a particularly useful feature in determining that nystagmus noted in adulthood is not of recent onset.

Congenital nystagmus is usually horizontal and conjugate. Vertical and torsional components are only occasionally present. The direction of any jerk component often varies with the direction of gaze, but an important feature in comparison to many forms of acquired nystagmus is that there is no additional vertical component on vertical gaze. In most patients with congenital nystagmus, there is a direction of gaze (null zone) in which the nystagmus is relatively quiet. If this null zone is away from primary position, a head turn may be adopted to place the eccentric position straight ahead. In a few cases, the position of the null zone varies to produce one type of periodic alternating nystagmus. Congenital nystagmus is usually decreased in intensity by convergence, and some patients will adopt an esotropia (nystagmus blockage). Anxiety and increased "effort to see" will often increase the intensity of congenital nystagmus and thus reduce visual acuity.

Once congenital nystagmus has been noted, it is important to identify any underlying sensory abnormality, if only to determine the visual potential. This may require electrodiagnostic studies. Extraocular muscle surgery is predominantly indicated for patients with a marked head turn. Supramaximal recessions of the horizontal rectus muscles reduce the intensity of congenital nystagmus, but the effect may be only temporary.

In general, latent nystagmus means nystagmus which increases in intensity when one eye is covered, and this is a characteristic feature of congenital nystagmus. There is also a specific type of latent nystagmus, known as (LN), which is predominantly seen in infantile esotropia. LN is a horizontal jerk nystagmus with the fast phase toward the side of the fixing eye-with the left eye covered, there is a rightward nystagmus and with the right eye covered a leftward nystagmus. LN also becomes more marked when one eye is covered, only then being apparent on clinical examination, but eye movement recordings show that the nystagmus is always present. (MLN) is a particular type of LN in which the nystagmus is always apparent on clinical examination. It occurs in patients with LN when binocular function is lost, ie, the equivalent of one eye being covered. This may be because of loss of sight in one eye or even from the development of a divergent squint. If binocular function is restored, MLN will revert to LN.

Acquired Pendular Nystagmus

Any child who develops bilateral visual loss before 6 years of age may also develop a pendular nystagmus, and indeed the acquisition of a pendular nystagmus during infancy necessitates further investigation. A specific syndrome of acquired pendular nystagmus in childhood is spasmus nutans. This is a bilateral, generally horizontal (occasionally vertical), fine, dissociated pendular nystagmus, associated with head nodding and an abnormal head posture. There is a benign form, which may be familial, with onset before age 2 and spontaneous improvement during the third or fourth year. Spasmus nutans may also rarely be the first manifestation of an anterior visual pathway glioma.

In adults, acquired pendular nystagmus is a feature of brainstem disease, usually multiple sclerosis or brainstem stroke. There may be horizontal, vertical, or torsional components or even a combination of components to produce oblique or elliptical trajectories. The syndrome of oculopalatal myoclonus characteristically develops several months after a brainstem stroke. There is a pendular nystagmus with synchronous movements variably involving the soft palate, larynx, and diaphragm as well as producing head titubation. (The term "myoclonus" is a misnomer since the abnormal movements are a form of tremor.) The associated hypertrophy of the inferior olivary nucleus in the medulla and other evidence suggest a disruption of the dentato-rubro-olivary pathway between the brainstem and the cerebellum as the underlying pathogenesis. Various drug treatments have been tried for adult acquired pendular nystagmus, of which baclofen, clonazepam, isoniazid, and gabapentin have produced the best though still limited results. Base-out prisms may also be tried.

Vestibular Nystagmus

Abnormalities of vestibular tone result in abnormal activation of the vestibulo-ocular pathways and abnormal neural drive to the extraocular muscles. Loss of function in the left horizontal semicircular canal is equivalent to activation of the right horizontal semicircular canal, as would normally be produced by a rightward head turn. The oculomotor response is conjugate leftward slow phase movement of the eyes. The corrective fast phase response is rightward in direction, and a right-beating horizontal nystagmus is thus generated. The pattern of response to dysfunction of one or more semicircular canals can be similarly derived to give the full possible range of peripheral vestibular nystagmus, though in clinical practice it is the effect of dysfunction of the horizontal canals that usually predominates. As a general rule, peripheral vestibular lesions are destructive and the fast phase of the resulting nystagmus is away from the side of the lesion. Since the neural signal of the vestibulo-ocular pathways is a velocity signal, the slow phase of peripheral vestibular nystagmus has a constant velocity. This gives rise to the characteristic saw-tooth waveform on eye movement recordings.

Peripheral vestibular nystagmus is not dependent upon visual stimuli and thus is still present in the dark, or with the eyes closed, as well as in blind individuals. It is, however, inhibited by visual fixation or, conversely, accentuated by wearing Frenzel's spectacles, and this is an important factor in the normal dampening over 2-3 weeks of peripheral vestibular nystagmus. Head position does not usually influence peripheral vestibular nystagmus except in benign paroxysmal positional vertigo, in which elicitation of the characteristic pattern of nystagmus with the Hallpike maneuver is a specific diagnostic feature. Other clinical features associated with peripheral vestibular disease are vertigo, tinnitus, and deafness, the latter two reflecting the close association between the vestibular and auditory systems. Causes of peripheral vestibular disease are labyrinthitis, Meniere's disease, trauma (including surgical destruction of one labyrinth), and vascular, inflammatory, or neoplastic lesions of the vestibular nerves.

Central vestibular nystagmus is an acquired jerk nystagmus due to disease in the central vestibular pathways of the brainstem and cerebellum. It has a variety of forms, but characteristic types are a purely torsional or vertical jerk nystagmus and the syndromes of downbeat and upbeat nystagmus, which are probably the result of imbalance in vestibular tone from the vertical semicircular canals. Central vestibular nystagmus is frequently elicited or enhanced by specific head positions, presumably as a result of modulation by input from the peripheral vestibular apparatus. It is not dampened by visual fixation and does not spontaneously abate in intensity with time. Other clinical features reflect the associated brainstem and cerebellar dysfunction and include abnormalities of smooth pursuit eye movements other than those due to the nystagmus itself. Causes of central vestibular nystagmus include lesions of the vestibular nuclei (brainstem demyelination, including multiple sclerosis, inflammation, and stroke, particularly thrombosis of the posteroinferior cerebellar artery leading to lateral medullary infarction-Wallenberg's syndrome).

Downbeat nystagmus is a downward-beating nystagmus, usually present in primary position. It is often most obvious on gaze down and to the side, when the nystagmus becomes oblique, with the horizontal component in the direction of lateral gaze. Downbeat nystagmus is characteristically associated with lesions at the cervicomedullary junction, notably Arnold-Chiari malformation and basilar invagination, and all patients should undergo MRI to exclude such lesions. Other causes are cerebellar degeneration, demyelinating disease, hydrocephalus, anticonvulsants, and lithium.

Upbeat nystagmus is characterized by an upward-beating nystagmus in primary position which usually increases though it may reduce in intensity on upgaze. It is virtually always the result of brainstem disease but occasionally reflects cerebellar disease. It is seen in brainstem encephalitis, demyelination, and tumors and also as a toxic side effect of barbiturates, alcohol, and anticonvulsants.

Gaze-Evoked & Gaze-Paretic Nystagmus

Maintenance of steady eccentric gaze is dependent upon the neural integrator system, which produces the tonic extraocular muscle activity necessary to overcome the viscous and elastic orbital forces acting to return the globe to primary position. Reduction in activity of the neural integrator results in eccentric gaze being negated by a slow drift of the globe toward primary position. Since the force acting to produce this central drift reduces with decreasing eccentricity, this slow drift has an exponentially decreasing velocity. Additional corrective fast eye movements, returning the eye to the desired eccentric position, result in nystagmus beating in the direction of gaze, whether it be horizontal, vertical, or oblique.

End-point nystagmus (see above) is the physiologic manifestation of the inability of the neural integrator to maintain steady eye position in extreme eccentric gaze. Gaze-evoked nystagmus is the result of pathologic failure of the neural integrator system. In its mildest form it manifests only on moderate horizontal gaze, whereas in its most severe form nystagmus is present with any movement away from primary position. In many cases of gaze-evoked nystagmus, there is also rebound nystagmus- following return of the eyes to primary position from a position of eccentric gaze, a jerk nystagmus beating away from the direction of the eccentric gaze develops after a latent period and lasts for a short period.

The neural integrator is situated in the brainstem but is highly dependent upon cerebellar inputs. Thus, gaze-evoked nystagmus may be a manifestation of either brainstem or, especially, cerebellar disease. Often there are other cerebellar eye movement abnormalities such as saccadic dysmetria and disruption of smooth pursuit. The most common causes of gaze-evoked nystagmus are cerebellar diseases, sedatives, and anticonvulsants. Cerebellopontine angle neoplasms, such as vestibular schwannomas (acoustic neuromas), may produce a combination of gaze-evoked nystagmus and a peripheral vestibular nystagmus beating toward the opposite side (Brun's nystagmus).

Reduction in the supranuclear input into the neural integrator or in the ability of the peripheral oculomotor system to facilitate its function will lead to nystagmus with the same basic characteristics as gaze-evoked nystagmus. Thus, conditions ranging from gaze palsy through oculomotor cranial nerve palsies and myasthenia gravis to extraocular muscle disease can manifest with nystagmus on eccentric gaze in the direction of the affected eye movements. This is termed gaze-paretic nystagmus and should be excluded whenever the possibility of a gaze-evoked nystagmus is being considered so as to avoid misdirected investigation.

Convergence-Retraction Nystagmus

Convergence-retraction nystagmus is a feature of the dorsal midbrain (Parinaud's) syndrome either from intrinsic lesions (tumor, hemorrhage, infarction, or inflammation) or extrinsic lesions, particularly pineal tumors and hydrocephalus. On attempted upgaze, which is usually defective, the eyes undergo rapid convergent movements with retraction of the globes. This is best elicited as the patient watches downward-moving stripes on an optokinetic tape or drum. Electromyographic studies have shown cocontraction of extraocular muscles and loss of normal agonist-antagonist reciprocal innervation. Convergence-retraction nystagmus may represent asynchronous, opposed, adducting saccades due to inappropriate activation of the medial rectus muscles.

Seesaw Nystagmus

Seesaw nystagmus is characterized by rising intorsion of one eye and falling extorsion of the other-and then the reverse. It may have a pendular or jerk waveform. Although it is uncommon, it occurs with acquired and congenital chiasmal lesions in association with a bitemporal hemianopia, and midbrain lesions. There does not appear to be a single underlying pathogenesis, but it is likely that dysfunction of the interstitial nucleus of Cajal or the rostral interstitial nucleus of the medial longitudinal fasciculus is important in the cases with midbrain disease.

Periodic Alternating Nystagmus

This is a direction-reversing nystagmus in which each direction can take 1-2 minutes before reversing. The acquired form occurs in pontomedullary junction disease (Arnold-Chiari malformation), multiple sclerosis, and cerebellar degeneration and may respond to baclofen. It may also occur with bilateral blindness and be suppressed if vision is restored. Periodic alternation may also be a feature of congenital nystagmus (see above).

MIMICS OF NYSTAGMUS

Abnormal spontaneous eye movements may be the result of unwanted saccadic eye movements (saccadic intrusions), which include square-wave jerks, macrosaccadic oscillations, ocular flutter, and opsoclonus. These are generally due to cerebellar disease. There is also a variety of abnormal eye movements that occur in coma, including ocular bobbing, ocular dipping, and ping-pong gaze. Superior oblique myokymia is a tremor of the superior oblique muscle leading to episodic monocular vertical oscillopsia.