Acquired Nystagmus

Updated: Jun 22, 2021
  • Author: Huy D Nguyen, MD, MBA; Chief Editor: Edsel B Ing, MD, MPH, FRCSC, PhD, MA  more...
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Overview

Background

Nystagmus is defined as the involuntary, periodic rhythmic ocular oscillation of the eyes that can either be physiologic (may not affect vision) or pathologic. [1]  Oscillopsia is defined as the illusion that the visual world is oscillating, or in motion, when it is in fact stationary. [1]  Nystagmus typically includes two movements: a slow first movement of the eye away from the visual target followed by a second, corrective movement that brings the eye back to the visual target. If the nystagmus has a slow initiating phase and a fast corrective phase it is termed jerk nystagmus. [1]  Conversely, if the second corrective movement is slow, the nystagmus is termed pendular nystagmus and is commonly characterized with sinusoidal oscillations that are approximately of equal amplitude and velocity. [1]  The former is more common. [2, 3]

Clinically, the characterization of nystagmus depends on a number of factors including: the degree of conjugacy, plane/s of oscillation, waveform, amplitude, frequency, direction/s of gaze, asymmetry and whether the nystagmus presents bilaterally or unilaterally. [4]  Notably, when the nystagmus appears unilateral, it is more often asymmetric rather than truly unilateral.

Nystagmus may be congenital or acquired. Congenital nystagmus (CN), also called infantile nystagmus, may be associated with afferent visual pathway abnormalities (sensory nystagmus) or with albinism, optic nerve hypoplasia or congenital cataracts. CN can also occur without central or ocular nervous system abnormalities (idiopathic CN). [4]  When acquired, it most often is caused by abnormalities of vestibular input. Many forms of acquired nystagmus may also be caused by disruptions of visual fixation, the vestibulo-ocular reflex and the mechanism that makes it possible to hold the gaze at eccentric eye positions. [4]  The remainder of this article focuses on acquired nystagmus.

To understand the mechanisms by which nystagmus may occur, it is important to discuss the means by which the nervous system maintains steady position of the eyes. Foveal centration of an object is necessary to obtain the highest level of visual acuity. Three mechanisms are involved in maintaining foveal centration of an object of interest: fixation, the vestibulo-ocular reflex, and the neural integrator (which allows for gaze holding in extreme, or eccentric, eye positions). Disruption in any of these components will predictably lead to an inability to maintain visual fixation. 

Fixation in the primary position involves the visual system's ability to detect drift of a foveating image and signal an appropriate corrective eye movement to refoveate the image of regard (ie, move the image to the central 1-2º of the visual field where visual acuity is highest). [5]  The vestibular system is intimately and complexly involved with the oculomotor system.

The vestibulo-ocular reflex is a complex system of neural interconnections that maintains foveation of an object during changes in head position. This reflex allows a stable image to be maintained on the retina during rapid head movements by rotating eyes in the opposite direction of the head movement, with a velocity that is equal to the head movement velocity. [6]  The proprioceptors of the vestibular system are the labyrinth mechanoreceptors in the semicircular canals of the of the inner ear which detect angular acceleration due to head rotation. [6]  Three semicircular canals are present in each ear: anterior, posterior, and horizontal.

The third mechanism is the neural integrator, which is required to maintain a steady gaze in extreme or eccentric eye positions. When the eye is turned in an extreme position in the orbit, for instance, the fascia and ligaments that suspend the eye exert an elastic force to return toward the primary position. To overcome this force, a tonic contraction of the extraocular muscles is required. A gaze-holding network called the neural integrator generates the required signal. The cerebellum, ascending vestibular pathways, and oculomotor nuclei are important components of the neural integrator.

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Pathophysiology

A disorder affecting any of the three components involved in maintaining the steady positioning of the eyes (ie, visual fixation, the vestibulo-ocular reflex or the neural integrator) may result in nystagmus. Both focal and diffuse disorders may cause nystagmus. The characteristics of the nystagmus, as well as associated signs and symptoms, help to localize the lesion and suggest possible etiologies.

Vestibular nystagmus

Generally, a reported illusion of movement suggests an imbalance within the vestibular system. A reported sensation of rotary movement that is accompanied by a nystagmus suggests a lesion involving the semicircular canals, while an illusion of linear acceleration indicates a disruption of the otoliths (utricle and saccule). [6]  Vestibular nystagmus may, therefore, be caused by a central or peripheral lesion to the vestibular system and distinguishing between both can be done using clinical exam findings and elements from elicited history. An isolated vertical or torsional nystagmus suggests a central lesion, whereas a vertical-torsional or horizontal-torsional nystagmus suggests a peripheral lesion. [6]  Unlike a peripheral nystagmus, a central nystagmus is not lessened by visual fixation but may even be worsened by it. [7]  Other distinguishing features of peripheral vestibular nystagmus include common co-involvement of tinnitus or hearing loss, severe vertigo symptoms, and duration of symptoms for days to weeks with improvement over time.

Central and peripheral vestibular lesions may also be distinguished using technologies that include three- dimensional eye movement vector analysis for the examination of individual semicircular canal function, measurement of subjective visual vertical for utricular testing and click evoked myogenic potentials for saccular testing. [6]  Although magnetic resonance imaging (MRI) could also be used to distinguish central and peripheral vestibular lesions, studies have shown that examination of eye movements is a more sensitive means of diagnosis. [8]  

Downbeat nystagmus

Downbeat nystagmus (DBN) is defined as a mostly central vestibular nystagmus with the fast phase beating in a downward direction. [9]  It results from impaired vertical gaze holding allowing slow upward drift with a downward corrective saccade. [10]  DBN is the most common form of acquired nystagmus and is typically associated with symptoms like unsteady gait, reduced visual acuity, and oscillopsia (subjective visual perception of constant movement of the surrounding environment when it is objectively stationary). [9]  The nystagmus is usually of maximal intensity when the eyes are deviated temporally and slightly inferiorly. With the eyes in this position, the nystagmus is directed obliquely downward. In most patients, removal of fixation (by Frenzel goggles, for example) does not influence slow phase velocity to a considerable extent; however, the frequency of saccades may diminish. [11] ]

The presence of downbeat nystagmus is highly suggestive of disorders of the cervicomedullary junction (most commonly the Arnold-Chiari malformation) or spinocerebellar degeneration (due to ataxia telangiectasia, for instance) which may accompany a positive family history. [11]   [12, 13]  This condition also may occur with bilateral lesions of the cerebellar flocculus and bilateral lesions of the medial longitudinal fasciculus, which carries optokinetic input from the posterior semicircular canals to the third nerve nuclei. It may also occur when the tone within pathways from the anterior semicircular canals is relatively higher than the tone within the posterior semicircular canals. Under such circumstances, the relatively unopposed neural activity from the anterior semicircular canals causes a slow upward pursuit movement of the eyes with a fast, corrective downward saccade. [14, 15]

The differential diagnosis for DBN is broad and includes structural or neoplastic lesions of the cerebellum or the cervicomedullary junction, stroke, trauma, paraneoplastic syndromes, drug effects, demyelinating conditions, brainstem encephalitis and nutritional deficiencies. [16]

Upbeat nystagmus

Upbeat nystagmus (UBN) is defined as nystagmus with the fast phase beating in an upward direction in the primary position. Daroff and Troost described 2 distinct types that are both secondary to drugs. [12]  The first type consists of a coarse, large amplitude nystagmus that increases in intensity with upward gaze and decreases in intensity with downward gaze. This type is suggestive of a lesion of the anterior vermis of the cerebellum and often accompanies infiltrating tumors, fourth ventricular masses, multiple sclerosis and nutritional cerebellar degeneration. [12]  The second type of UBN consists of a small amplitude nystagmus that decreases in intensity with upward gaze and increases in intensity with downward gaze. This type is suggestive of lesions of the medulla. [12]

UBN may occur when the tone within the pathways of the posterior semicircular canals is relatively higher than the tone within the anterior semicircular canals, and it can occur from lesions of the ventral tegmental tract or the brachium conjunctivum, which carry optokinetic input from the anterior semicircular canals to the third nerve nuclei. Generally, UBN are often reported with lesions of the medulla, including the perihypoglossal nuclei and adjacent vestibular nucleus, both of which are required for gaze holding, the ventral tegmentum and the anterior vermis of the cerebellum. [17]

Torsional (rotary) nystagmus

Torsional (rotary) nystagmus refers to a rotary movement of the globe about its visual axis. Nystagmus that is purely torsional, or rotary, is rare and indicative of a disorder of the central vestibular system. [18]  Torsional nystagmus is typically accentuated on lateral gaze. It is worth noting that most vestibular nystagmus have a torsional component superimposed on a horizontal or vertical nystagmus.

A medullary lesion causes a torsional nystagmus that usually beats towards the shoulder opposite the lesion due to unopposed afferents from the vertical semicircular canal on the intact side. This results in a slow pathologic ipsilesional torsional drift and a contralesional torsional fast phase. [18]

A midbrain lesion, however, will cause a slow contralesional torsional drift that is combined with an ipsilesional torsional fast phase (ie, torsional gaze evoked nystagmus). [18]  A unilateral lesion of the rostral interstitial nucleus of the medial longitudinal fasciculus may result in a contralesional torsional nystagmus. [18]

Furthermore, this condition may occur with lesions of the anterior and posterior semicircular canals on the same side (eg, lateral medullary syndrome). Lesions of the lateral medulla may also produce a torsional nystagmus with the fast phase directed away from the side of the lesion. This type of nystagmus can be accentuated by otolithic stimulation by placing the patient on their side with the intact side down (If the lesion is on the left, the nystagmus is accentuated when the patient is placed on his right side).

Pendular nystagmus

Pendular nystagmus is a sinusoidal, multivectorial nystagmus (ie, horizontal, vertical, circular, elliptical) that presents distinctly based on whether it is congenital or acquired. [4]  Congenital pendular nystagmus present as binocular, conjugate, horizontal nystagmus with variable wave forms which change to a jerk nystagmus on lateral gaze. [19]  Acquired pendular nystagmus presents more variably and may be unilateral or bilateral, conjugate or disconjugate with a wave form that is independent of eye position. [19]  Pendular nystagmus may also present in the context of other rhythmical movements occurring at similar frequencies in other parts of the body as in the “oculo-palatal-myoclonus” syndrome. [19]  Patients with acquired pendular nystagmus may also present with tremors in the head, neck and upper limbs. [19]

Pendular nystagmus oscillations present with an equal velocity in each direction (no distinct fast or slow phase) and may suggest brain stem or cerebellar dysfunction including disorders of myelin accompanying the syndrome of oculopalatal myoclonus, Whipple’s disease or drug toxicities. A brainstem lesion, confirmed by postmortem examination, was identified as the underlying cause of the concurrent acquired pendular nystagmus and “oculo-palatal-myoclonus” syndrome. [20]  Often, there is marked asymmetry and dissociation between the eyes. [21, 22]

Horizontal nystagmus

Horizontal nystagmus is a well-recognized finding in patients with a unilateral disease of the cerebral hemispheres, especially with large, posterior lesions. It often is of low amplitude. Such patients show a constant velocity drift of the eyes toward the intact hemisphere with fast phase directed toward the side of the lesion.

Seesaw nystagmus

Seesaw nystagmus is a pendular oscillation that consists of elevation and intorsion of one eye and the synchronous depression and extorsion of the other eye, which alternates every half cycle. Seesaw nystagmus typically have a pendular waveform. [23]  This striking and unusual form of nystagmus may be seen in patients with parasellar optic chiasm lesions (eg, pituitary tumors), suggesting loss of the crossed visual inputs from the decussating fibers of the optic nerve at the level of the chiasm as the cause, achiasma (associated with a unique form of nystagmus in which the torsional components are conjugate and the vertical components are disjunctive), tumors in the diencephalon, or lesions in the rostral midbrain. [4]  This type of nystagmus is not affected by otolithic stimulation.

Notably, a seesaw nystagmus occurs at a higher amplitude and lower frequency on downward gaze, and a low amplitude and higher frequency on upward gaze. [24]

Gaze-evoked nystagmus

Gaze-evoked nystagmus (GEN) is produced by the attempted maintenance of an extreme or eccentric eye position. [25]   It is the most common form of nystagmus. Gaze-evoked nystagmus is usually due to a structural lesion that leads to a deficient eye position signal in the neural integrator network. Thus, the eyes cannot be maintained at an eccentric orbital position and are pulled back toward primary position (ie, the straight ahead gaze) by the elastic forces of the orbital fascia. Then, corrective saccade moves the eyes back toward the eccentric position in the orbit. [26]

Gaze-evoked nystagmus may be caused by structural lesions that involve the neural integrator network, which is dispersed between the vestibulocerebellum, the medulla (region of the nucleus prepositus hypoglossi and adjacent medial vestibular nucleus [NPH/MVN]), and the interstitial nucleus of Cajal (INC). Patients recovering from a gaze palsy go through a period where they are able to gaze in the direction of the previous palsy, but they are unable to sustain gaze in that direction; therefore, the eyes drift slowly back toward primary position followed by a corrective saccade. When this is repeated, a gaze-evoked or gaze-paretic nystagmus results. Gaze-evoked nystagmus may also be caused by cerebellar disease or as a side effect of alcohol use or the use of sedative or anticonvulsant drugs. [4]  If GEN presents asymmetrically with a rebound primary gaze, or with associated complaints like nausea/vomiting, headaches (especially when awakening) or loss of motor skills (gradual or sudden) then the etiology of the nystagmus most likely involves a disorder involving the brainstem or cerebellum. [25]

Gaze-evoked nystagmus often is encountered in healthy patients; in which case, it is called end-point nystagmus. End-point nystagmus can be differentiated from gaze-evoked nystagmus as it is not sustained, has a lower amplitude and is not associated with other ocular motor abnormalities.

There are several types of clinically significant GEN including the central nervous system defect GEN which is asymmetric and is caused by brain stem or cerebellar disease. [25]  In this type of GEN, the nystagmus has a higher amplitude at the side of gaze towards the side of the lesion. If the central nervous system defect GEN is caused a cerebellar disease, then the jerk phase of the nystagmus is directed opposite the lesion. [25]  The other type of GEN is termed gaze paretic GEN and is caused by the weakness of 1 or more extraocular muscles or the disruption of their innervations. [25]  Gaze paretic GEN is commonly seen in myasthenia gravis (MG) or Guillan Barre syndrome patients, and the direction of the nystagmus corresponds to the direction of action of the weakened extraocular muscle. [25]  Unlike a GEN caused by MG, a CNS defect GEN maintains the same amplitude during examination and throughout the day. Lastly, the third type of GEN, called toxic GEN, is caused by oral sedatives, barbiturates or anticonvulsant drugs and will cease 3-4 days after cessation of drug use. [25]    

Some normal individuals develop sustained physiological GEN in a lateral gaze of 40 degrees. [27]  This form of nystagmus has an amplitude that is less than 3 degrees and is most often symmetric in both eyes. [28]  Physiological GEN should cease if the visual target is brought back to the center where there is binocular foveation. [18]

Spasmus nutans

Spasmus nutans is a rare condition with the clinical triad of: asymmetric or monocular nystagmus, head nodding (2-3 Hz), and torticollis. [30] A study suggests that head nodding is normal compensatory vestibulo-ocular reflex to control the nystagmus in spasmus nutans. [28]  Onset is from age 4-14 months with disappearance by 5 years. Rarely, it may be present to age 5-6 years. Subclinical nystagmus persists until at least 5 to 12 years of age. [28]  The nystagmus typically consists of small-amplitude, high frequency oscillations and usually is bilateral, but can also be monocular, asymmetric, variable in different positions of gaze, disconjugate, conjugate or purely uniocular. [29]

Spasmus nutans is usually benign; however, it has been reported with more serious conditions like parasellar and hypothalamic tumors and therefore warrants neuroimaging. Associated retinal disorders (such as congenital stationary night blindness) may warrant electroretinogram when suspected. Reports have also been made of a completely resolved spasmus nutans that preceded the diagnosis of a chiasmal glioma. [18]

Periodic alternating nystagmus

Periodic alternating nystagmus (PAN) is a conjugate, horizontal jerk nystagmus with the fast phase beating in one direction for a period of approximately 1-2 minutes. The nystagmus has an intervening neutral phase, termed a null period, lasting 10-20 seconds; the nystagmus begins to beat in the opposite direction for 1-2 minutes; then, the process repeats itself. The presumed mechanism is disruption of the vestibulo-ocular tracts at the pontomedullary junction. [17]

Acquired PAN is often associated with posterior fossa malformations, demyelinating conditions, spinocerebellar degeneration and anticonvulsant drug use. [30]  PAN has also been reported in the context of visual or vestibular loss or as a short term consequence of sensory deprivation (due to ocular media opacities, for instance). [30]  Compensatory, involuntary head movements may develop to maintain visual fixation in the presence of PAN. [30]

Abducting nystagmus of internuclear ophthalmoplegia

Abducting nystagmus of internuclear ophthalmoplegia (INO) is, as the name implies, and adaptive nystagmus in the abducting eye contralateral to a medial longitudinal fasciculus (MLF) lesion. By Hering’s law of equal innervation, the adduction deficit leads to a compensatory increase in signal that equally increase the drive to the yoke muscle in the fellow eye, causing a far abduction followed by a corrective saccade. [19]

Opsoclonus/saccadomania

Opsoclonus/saccadomania is defined as involuntary, arrhythmic, conjugate, multidirectional saccades and is associated with viral illness (West Nile virus, lyme disease, HIV), neoplasms (neuroblastoma (children), non-Hodgkin’s lymphoma, renal adenocarcinoma and small cell lung cancer), allogeneic hematopoietic stem cell transplantation, celiac disease, stroke, trauma, posterior reversible encepthalogy syndrome, central nervous system tumors, and hyperosmolar nonketotic coma. [31]  Opsoclonus may also be associated with cerebellar, brainstem or diffuse cerebral injury. [18]  

Evidence suggests an autoimmune mechanism may underlie opsoclonus with newly identified autoantibodies including antineuroleukin, antigliadin, antiendomysial and anti-CV2 binding autoantigens located on postsynaptic density or on the cell surface of neurons or neuroblastoma cells. [32]  Although some opsoclonus patients are seronegative, it is suggested that humoral and cell mediated mechanisms drive the pathogenesis of opsoclonus. [31]

Latent nystagmus/fusion maldevelopment syndrome

Latent nystagmus/fusion maldevelopment syndrome is thought to be caused by unequal inputs into both eyes, such as unilateral vision loss, a latent nytsgamus primarily develops in patients with congenital estropia. [32]  A latent nystagmus is greatest in magnitude when the uncovered eye is abducted and is reduced when the eye is adducted. Latent nystagmus is often benign, has declining slow phase and is superimposed on a congenital nystagmus. [18]  Neuroimaging is not indicated in latent nystagmus if the clinical exam demonstrates waveform direction change with occlusion and no history of prematurity, as the condition does not generally imply a central nervous system lesion or defect. [18]  

Dissociated nystagmus

Typically used as the description for eye movement findings in internuclear ophthalmoplegia (INO), a dissociated nystagmus refers to a disorder in which the eyes move in the same direction but with asymmetrical movement amplitudes. [18]  The abducting eye may exhibit a nystagmus with impaired adduction of the fellow eye in a dissociated nystagmus. [18]  INO is most commonly caused by demylineating disorders and brainstem strokes which result in the disruption of the medial longitudinal fasciculus, which is required for smooth and coordinated movements of the eyes. [18]

Rebound nystagmus

In rebound nystagmus, the patient’s eyes beat in the direction of re-fixation upon being asked to look back to the primary gaze after maintaining an eccentric eye gaze for several seconds. [33]  A rebound nystagmus implies some defect in the flocculus or paraflocculus, involves eye beating away from a unilateral lesion and may be explained as an effort of the brain to compensate for the centripetal drift of pathologic endgaze nystagmus. [18]  

Heimann Bielchowsky phenomenon

Patients with the Heimann Bielchowsky Phenomenon (HBP) have mononuclear, pendular nystagmoid movements that are slow, coarse and of variable amplitudes in an eye with significant visual loss. [34]  This phenomenon is thought to be caused by disruptions to the monocular visual stabilization system or the fusional vergence mechanism. [34]

 

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Epidemiology

Mortality/morbidity

Mortality and morbidity are dependent upon etiology.

Age

All of the acquired nystagmus described earlier, except spasmus nutans, can occur at any age. Onset of spasmus nutans is in infants aged 4-14 months with disappearance by age 5 years. Subclinical nystagmus, following the resolution of spasmus nutans, persists until at least 5 to 12 years of age. [35]

Congenital nystagmus (juvenile nystagmus) is classified as onset before 6 months of age and is discussed in a separate article.

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Prognosis

Prognosis is dependent upon etiology.

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