Acquired Nystagmus 

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

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.

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]

 

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.

Prognosis

Prognosis is dependent upon etiology.

 

Presentation

History

A thorough history is important to help determine the etiology of the nystagmus. Important aspects of the history include the following:

  • Age of onset of the nystagmus, whether it is constant or intermittent, the presence of any aggravating or alleviating factors (eg, head or body positions).
  • Presence or absence of vertigo, oscillopsia (an illusory motion of the seen world; could either be rotary or linear), [36]  and sensation of disequilibration suggest a lesion of the vestibular system.
  • Associated deafness or tinnitus suggest peripheral lesions of the vestibular system.
  • Presence of diplopia, particularly in certain positions of gaze. For example, patients with INO may report diplopia only on lateral gaze or intermittent blurring of vision.
  • Ask questions regarding the presence of any associated symptoms, such as symptoms related to demyelinating disease (eg, a history of vision loss, eye pain, or numbness or weakness of the extremities), symptoms related to cerebrovascular accident (eg, hemiplegia), and predispositions to thiamine deficiency (eg, alcoholism, bariatric surgery).
  • Medications such as anticonvulsants, sedatives, barbiturates, lithium may be associated with nystagmus. Gaze evoked nystagmus is associated with alcohol use.  

Physical

Neuro-ophthalmic examination

A complete neuro-ophthalmic examination is imperative in patients with nystagmus. Aside from a complete ophthalmic examination, including visual acuity, measurement and reactivity of the pupils to light and accommodation, measurement of intraocular pressure, testing the function of extraocular muscles, and anterior and dilated posterior segment examination, other important aspects of the examination include the following:

Observing the nystagmus with regard to plane (ie, horizontal, vertical, torsional, relative to the visual axis), frequency, amplitude, direction, and conjugate/disconjugate is important. Isolated rotary nystagmus almost always represents central vestibular dysfunction; vertical-torsional or horizontal-torsional is associated with peripheral vestibular dysfunction.[6]

Note whether the character of the nystagmus changes in certain directions of gaze.

Nystagmus due to vestibular disease increases in intensity when the eyes are turned in the direction of the saccade (fast phase)(ie, Alexander law).

A horizontal nystagmus due to peripheral vestibular imbalance remains horizontal on upward and downward gaze. Note the presence or absence of compensatory head nodding or torticollis (spasmus nutans).

Note whether the nystagmus dampens with fixation. Fixation inhibits nystagmus and vertigo due to peripheral lesions of the vestibular system.

Optokinetic nystagmus (OKN) drum

The optokinetic reflex allows us to maintain foveation on a moving object when the head is stationary (ex., observing individual telephone poles on the side of the road as one travels by them in a car). OKN is involuntary but may be suppressed if the patient looks above or below the moving object.  The reflex develops at about age 6 months and is produced as the patient pursues a moving object, while maintaining a stationary head position, and then experiences a corrective saccade in the opposite direction to follow the next moving target. Note the direction of OKN drum if it induces a change in nystagmus magnitude or direction.

Insufficient suppression of the primitive optokinetic response is believed to drive the development of latent and congenital nystagmus.[18]  One may observe a paradoxical reversal of the optokinetic nystagmus response in patients with congenital nystagmus.[18]  Patients with horizontal nystagmus with unilateral hemispheric lesions, especially parietal or parietal-occipital lesions, show impaired optokinetic nystagmus when the drum is rotated toward the side of the lesion.

The OKN drum may be used as an estimate of visual acuity. The striped drum is equivalent to a vision of counting fingers when held at a distance of 3-5 feet from the patient. The further the drum is from the patient, the better the visual acuity must be to respond normally to the moving drum.

Confrontational visual field testing may reveal gross field defects that may help determine the presence and/or location of an intracranial lesion.

For Romberg testing have the patient stand with eyes closed and feet together. If a defect in the vestibular system is present, the patient tends to fall toward the side of the lesion.

Oculocephalic reflex (doll’s head phenomenon)

The oculocephalic reflex develops within the first week of life and essentially represents a vestibulo-ocular reflex normally suppressed in a conscious individual that attempts to turn the head to fixate on an object. The intact reflex determines that the infranuclear pathways are intact and therefore helps in localizing the lesion. This test consists of the rapid rotation of the patient’s head in a horizontal or vertical direction while holding their eyelids open to examine their eyes. With intact vestibular nuclei and medial longitudinal fasciculi, the eyes move conjugately in the opposite direction of the head turn. In a patient with a negative oculocephalic reflex, the eyes remain at midline and do not move as the head rotates. A similar test may be performed for vertical head movements. Alternatively, the test may be performed by having the patient extend the arm out in front of the body and fixate on the outstretched thumb. Patients should be instructed to rotate their torso back and forth about their longitudinal axis such that the thumb remains in front of the body at all times.

Patients with the ability to suppress the oculocephalic reflex should be able to maintain fixation on their thumb while rotating. An abnormal test result would show the patient continuously losing fixation of the thumb.

Caloric testing

Caloric testing is used to assess the function of the peripheral vestibular system and involves up to four irrigations of water or air into the external ear meatus.[36]  Caloric irrigations create a thermal gradient, or a temperature difference, between the external auditory canal and the endolymph in the horizontal semicircular canal of the inner ear, which in turn changes the density of the endolymph causing it to rise or sink (depending on the temperature of the irrigation fluid).[36]  The rising or sinking of the endolymph deflects the cupula and elicits an excitatory or inhibitory neural response, thus inducing nystagmus. Changes in the temperature and density of the endolymph due to the temperature of the irrigation water mimic those caused by rotations of the head.[36]  The nystagmus response to caloric testing peaks 1 minute after the initiation of irrigation, falls to 50% after another 30-60 seconds and becomes minimal or disappears completely after one more minute.[36]  It has been suggested that the nystagmus dampens before the resolution of the thermal gradient caused by irrigation due to central nervous system adaptation.[36]

While sitting erect, the patient tilts the head back 60°. While in supine, the patient elevates the head 30°; this brings the horizontal semicircular canals into the vertical plane.

The external auditory canal is irrigated with cold or hot water. Cold water instilled into the right ear causes the endolymph in the right semicircular canal to cool and sink. This movement of endolymph is the same movement induced by a rotation of the head to the left, inducing a horizontal nystagmus directed to the left (ie, to the opposite side the water was placed). Warm water in the same ear produces the opposite effect (ie, a horizontal nystagmus directed to the right or toward the same side the water was placed); ie, cold-opposite, warm-same (COWS).

Otolithic stimulation

Note whether the character of the nystagmus changes with otolithic stimulation. Failure to respond to otolithic stimuli suggests a peripheral vestibular disease or lesion.

Note whether any body position exacerbates the nystagmus due to otolithic modulation. In an acquired downbeat nystagmus, for instance, the nystagmus is made more prominent when the patient is prone or after resting in the supine or prone position for long periods of the day.[37]

A full neurologic examination may reveal the diagnosis. In patients with vertical pendular nystagmus, associated palatal undulation suggests oculopalatal myoclonus.

Visual acuity

In patients with latent nystagmus, acuity should be measured by fogging the contralateral eye with a hyperopic lens.

 

Causes

Seesaw nystagmus may be caused by the following:

  • Parasellar optic chiasm lesions (eg pituitary tumors)
  • Achiasma
  • Tumors in the diencephalon
  • Lesions in the rostral midbrain.
  • Visual loss secondary to retinitis pigmentosa

Downbeat nystagmus may be caused by the following:

  • Disorders of the craniocervical junction (most commonly the Arnold-Chiari malformation)
  • Spinocerebellar degeneration (due to ataxia telangiectasia, for instance)
  • Bilateral lesions of the medial longitudinal fasciculus
  • Lesions of the vestibulocerebellum and underlying medulla, including:
    • Microvascular disease with vertebrobasilar insufficiency
    • Brain stem encephalitis
    • Tumors at the foramen magnum (eg, meningioma, cerebellar hemangioma)
    • Trauma
    • Drugs (eg, alcohol, lithium, antiseizure medications)
    • Nutritional (eg, Wernicke encephalopathy, parenteral feeding, magnesium deficiency)
  • Heat stroke
  • Approximately 50% have no identifiable cause.

Upbeat nystagmus may be caused by the following:

  • Lesions of the anterior vermis of the cerebellum
  • Infiltrating tumors
  • Fourth ventricular masses
  • Multiple sclerosis
  • Nutritional cerebellar degeneration.
  • Medullary lesions, including perihypoglossal nuclei, the adjacent medial vestibular nucleus, and the nucleus intercalatus (structures important in gaze holding)
  • Benign paroxysmal positional vertigo

Periodic alternating nystagmus may be caused by the following:

  • Posterior fossa malformations
  • Demyelinating conditions
  • Spinocerebellar degeneration
  • Anticonvulsant drug use
  • Visual or vestibular loss
  • Transient consequence of sensory deprivation, ex. ocular media opacities
  • Lesions of the vestibular nuclei
  • Head trauma
  • Encephalitis
  • Syphilis

Pendular nystagmus may be caused by the following:

  • Disorders of myelin accompanying oculopalatal myoclonus
  • Wipple’s disease
  • Drug toxicities
  • Brainstem or cerebellar dysfunction
  • Monocular or binocular visual deprivation
  • Internuclear ophthalmoplegia

Spasmus nutans may be caused by the following:

  • Usually benign
  • Parasellar and hypothalamic tumors
  • Retinal disorders
  • Chiasmal, suprachiasmal, or third ventricle gliomas may cause a condition that mimics spasmus nutans.

Torsional nystagmus

  • Lesions of the anterior and posterior semicircular canals on the same side (ex. lateral medullary syndrome(Wallenberg syndrome))
  • Lesions of the lateral medulla

Abducting nystagmus of internuclear ophthalmoplegia may be caused by the following:

  • Demyelinating conditions
  • Brain stem stroke

Gaze evoked nystagmus may be caused by the following:

  • 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)
  • Recovery from a gaze palsy
  • Brainstem or cerebellar disease
  • Side effect of alcohol or the use of oral sedatives, barbiturates or anticonvulsant drugs
  • Weakness of 1 or more extraocular muscles or the disruption of their innervations
  • Myasthenia gravis or Guillan Barre syndrome

 

 

DDx

Diagnostic Considerations

Congenital nystagmus (infantile nystagmus)

Infantile, or congenital, nystagmus typically presents between 2-4 months of life when visual fixation normally develops and is distinct from acquired nystagmus in that it is conjugate, has mixed jerk and pendular waveforms, has a null point and a lack of oscillopsia.[18]  Visual loss, if present, is stable and not progressive. In infants who present with nystagmus, the most important distinction to make is between congenital nystagmus and spasmus nutans.[18]  Congenital nystagmus classically present as a horizontal nystagmus with a pendular waveform but may also be torsional or veritcal (rare).[18]  Congenital nystagmus may be sub-classified into congenital motor nystagmus (presents with relatively normal vision, normal fundus, and normal neurological examinations) and congenital sensory nystagmus (presents with poor vision).[18]  An infant that presents with a nystagmus must undergo a careful assessment of visual acuity and fundus appearance to classify their congenital nystagmus.[18]  If the nystagmus is caused by a retinal disorder, it typically presents with moderately to severely diminished vision (congenital sensory nystagmus), paradoxical pupil constriction when the light is turned off, oculodigital reflex, photophobia or high myopia.[18]  Foveal hypoplasia, along with transillumination of the retina with a slit lamp can be used to identify ocular albinism.[18]  In those with congenital sensory nystagmus or those whose examination results is inconclusive, MRI imaging of the brain, electroretinography and OCT would likely provide aid in diagnosis.[18]  If the patient presents with a congenital motor nystagmus but is otherwise normal, only close follow up is necessary.[18]  The presence of a pale optic disk, a history of progressive visual loss, or unilateral vertical nystagmus should suggest that the nystagmus is acquired and possibly due to a neoplasm involving the visual system.[18]  Such patients require MRI neuroimaging.[18]

Voluntary nystagmus

Voluntary nystagmus refers to a series of rapidly alternating horizontal saccades that occur usually in bursts of 5-10 seconds, are produced by individuals for gain or amusement, and may be seen in families.[18]  The nystagmus itself is a high frequency (3-42Hz), low amplitude back and fro oscillation that cannot be sustained.[18]  Patients with voluntary nystagmus complain of blurry vision and oscillopsia, and their ocular oscillation may be accompanied by lid fluttering and squinting.[18]  Voluntary oscillations may be interrupted by having the patient pursue a visual target or with distraction.[18]

Convergence retraction nystagmoid movements

Although not a true nystagmus because it lacks slow phases and is just opposing saccades, it is a potentially localizing eye movement disorder similar to nystagmus. Convergence retraction nystagmus may be elicited by having the patient look up quickly or by moving an optokinetic tape downward.[18]  The deficit in upgaze results in increased signal to other muscles, including the dominant medial recti, that manifest as a convergence and co-contractions of muscles that manifest as retraction. It is a sign of pretectal dysfunction and is usually accompanied by other neurological symptoms like upgaze palsy, pupillary light dissociation, and eyelid retraction.[18]  Dorsal midbrain lesions may cause convergence retraction nystagmoid movements.[18]

Thyroid associated ophthalmopathy may present with eyelid retractions, decreased upgaze and globe retractions which can mimic convergence retraction nystagmus.[18]  Lack of pupillary abnormalities in addition to the presence of exophthalmos, conjunctival injections, eyelid edema and positive forced ductions distinguish the two pathologies.[18]

 

Differential Diagnoses

 

Workup

Imaging Studies

Imaging studies

Any patient who develops nystagmus without an identifiable cause (eg, Ménière disease, drug toxicity) or with localizing neurologic deficits should undergo neuroimaging. A complete history and neuro-ophthalmic examination are crucial to localizing an intracranial disorder. Communication with the neuroradiologist regarding such localization is important in ensuring that regions of the brain suggestive of a disorder are imaged adequately.

Central vestibular forms of nystagmus are always pathologic and deserve a thorough evaluation. MRI is the preferred method of neuroimaging. Although MRI studies may be used to distinguish between central and peripheral vestibular lesions, studies have shown that examination of eye movements allows for more accurate diagnosis.

Infantile, or congenital, nystagmus typically manifests between 2-4 months of life when visual fixation normally develops and is distinct from acquired nystagmus in that it is conjugate, has mixed jerk and pendular waveforms, has a null point, and lacks oscillopsia. Visual loss, if present, is stable and not progressive. The presence of a pale optic disc, a history of progressive visual loss, or unilateral vertical nystagmus should suggest that the nystagmus is acquired and possibly due to a neoplasm involving the visual system. Such patients require neuroimaging with MRI.

Optic chiasm or third ventricle gliomas can cause a condition that mimics spasmus nutans. All children with spasmus nutans should undergo MRI imaging and a complete neuro-ophthalmic examination. Signs suggestive of a neoplastic etiology include visual acuity loss, relative afferent pupillary defect, optic disc pallor, endocrinologic abnormalities like poor feeding or dicephalic syndrome, age of onset before 12 months, and vertical or seesaw nystagmus. The neoplasm mosy commonly associated with spasmus nutans is an optic pathway glioma.[18]  Lower socioeconomic status, parental drug and drug abuse, African American or Hispanic ethnicities are more associated with spasmus nutans than congenital nystagmus.[18]  If the decision is made to delay MRI in children without neurologic deficit, they should be observed closely for onset of neurologic deficits.

Although not a true nystagmus because they lack slow phases and are just opposing saccades, convergence retraction nystagmoid movements are a potentially localizing eye movement disorder that is similar to nystagmus. Convergence retraction nystagmus may be elicited by having the patient look up quickly or by moving an optokinetic tape downward.[18]  The deficit in upgaze results in increased signal to other muscles, including the dominant medial recti, that manifest as a convergence and co-contractions of muscles that manifest as retraction. It is a sign of pretectal dysfunction and is usually accompanied by other neurological symptoms like upgaze palsy, pupillary light dissociation and eyelid retraction.[18]  Dorsal midbrain lesions may cause convergence retraction nystagmoid movements.[18]

Thyroid associated ophthalmopathy may present with eyelid retractions, decreased upgaze and globe retractions which can mimic convergence retraction nystagmus.[18]  Lack of pupillary abnormalities in addition to the presence of exophthalmos, conjunctival injections, eyelid edema and positive forced ductions distinguish the two pathologies.[18]

 

 

Other Tests

Electronystagmographs record eye muscle contractions to evaluate the direction and velocity of nystagmus. It may be used to evaluate low-amplitude nystagmus that is difficult to discern on examination. This study can help determine the type and velocity of the nystagmus, which is important in directing therapy.

 

Treatment

Medical Care

Any medications that may be causing the nystagmus should be discontinued in conjunction with the patient's internist, neurologist, and/or pediatrician.

Significant refractive errors should be corrected. Contact lenses may be preferred over spectacles because the patient may continue to look through the optical center of the contact lens if a head turn secondary to the presence of a null zone exists. Contact lenses may also reduce nystagmus by reducing abnormal eye movements and enhancing sensory feedback. This usually only applies to congenital nystagmus.[16]  Topical brinzolamide was also found to improve acuity and the characteristics of central nervous waveforms in the primary position null zone in congenital nystagmus.[18]

Prism therapy may be useful for inducing convergence or shifting the null point to the primary position (ie, straight ahead gaze). Base-out prisms (eg, 7 diopters) with a -1.00 myopic correction may be used for convergence damping in infantile nystagmus. Base-out prisms (to induce convergence) have also been described to treat downbeat nystagmus with a pseudocycloid waveform.[37]  Prisms may be useful prior to considering surgery for a head turn. Placing prisms over both eyes with the apices directed towards the preferred gaze position may help shift the line of sight to the primary, straight ahead gaze, thus eliminating the need to adopt abnormal head positions. Fresnel prisms directed with the base opposite the null zone (eg, for a right face turn with a null zone in left gaze, the prism over the right eye would be base out and a prism over the left eye would be base in). Null zones are more characteristic of congenital nystagmus; thus, prisms may not be applicable to most forms of acquired nystagmus.[37]

 

Surgical Care

Surgical treatment may include the following:

  • Removing the inciting etiology if possible (ex. intracranial tumors, ocular media opacities).Botulinum toxin may be used to treat patients with acquired nystagmus to dampen the nystagmus and to improve visual acuity and to decrease oscillopsia. Botulinum toxin may also be used to eliminate compensatory head tilting and tremors.
    • The toxin may be injected into the rectus muscles (2.5 U per muscle) or may be given as a retrobulbar injection [17]  (10-25 U in 0.1-1 cm3).
    • Multiple injections usually are necessary as the effect of the toxin wears off.
    • Patients whose symptoms improve with botulinum toxin injection may be able to discern when the effect of the toxin begins to diminish as the symptoms may begin to recur.
    • A disadvantage of this treatment option is that botulinum toxin impairs all types of eye movement (ex. saccades, smooth pursuit).
    • Complications of toxin injection include ptosis, diplopia, increase of nystagmus in the noninjected eye, and, rarely, globe rupture.
  • Extraocular muscle surgery (Anderson-Kestenbaum procedure) for correction of nystagmus is based on surgically shifting the null zone into primary position (straight ahead position). Again, null zones are more characteristic of congenital nystagmus; thus, they may not be applicable to most forms of acquired nystagmus. Tetonomy, a controversial procedure in which all four recti muscles are detached and re-attached at their original insertion sites, has been reported to improve foveation and vision. Tetonomy combined with strabismus surgery has been shown to improve visual function in patients with ocular misalignment and congenital nystagmus. [18]  Retroequatorial rectus muscle recessions have been shown to be effective in treating acquired nystagmus without a null point, as has extraocular muscle tenotomies with reattachment. [17, 38]

Consultations

Consider neurologic or neuro-ophthalmic consultation.

Neurosurgical or oncologic consultation should be sought in cases with a neoplastic etiology.

Otolaryngologic consultation should be considered in cases of benign positional vertigo or other peripheral vestibular disorders.

Long-Term Monitoring

Regular office visits are useful to monitor nystagmus.

 

Medication

Medication Summary

The goals of pharmacotherapy are to reduce morbidity and to prevent complications.

The potassium channel blocker 3,4-diaminopyridine has been suggested as an off-label treatment for downbeat nystagmus.[2, 39]

Anticonvulsants

Class Summary

Increases GABA synthesis and release and decreases GABA degradation. Used for acquired pendular nystagmus. [[37] ]

Gabapentin (Neurontin)

May reduce nystagmus, improve visual acuity, and reduce oscillopsia in patients with acquired pendular nystagmus. Relatively few drug interactions and mild, tolerable side effects.

Clonazepam (Klonopin)

Used for downbeat and seesaw nystagmus. Suppresses muscle contractions by facilitating inhibitory GABA neurotransmission and other inhibitory transmitters. Concentrations of clonazepam may increase if it is given in conjunction with oral antifungal agents due to the inhibition of cytochrome P450-3A. Common side effects include ataxia, dizziness, depression and amnesia. 

Muscle relaxants, GABA agonists

Class Summary

Use for periodic alternating nystagmus, downbeat and upbeat nystagmus, and seesaw nystagmus. [[40] ,[37] ]

Baclofen (Lioresal)

Periodic alternating oscillopsia may be a major complaint in patients with periodic alternating nystagmus and may be cured by the use of baclofen. May cause an increased risk of respiratory and central nervous system depression if used with narcotics, especially propoxyphene. 

 

Neuromuscular blocker agents

Class Summary

Blocks neuromuscular transmission at cholinergic junctions by preventing release of acetylcholine from nerve terminals. Decreases nystagmus and improves visual acuity. [[41] ]

OnabotulinumtoxinA (BOTOX®)

Treats excessive, abnormal contractions associated with blepharospasm. Binds to receptor sites on motor nerve terminals and inhibits release of acetylcholine, which, in turn, inhibits transmission of neural impulses at neuromuscular junctions. May also be useful for suppressing compensatory head tilting or tremors that develop to allow visual fixation in the presence of a nystagmus.

Reexamine patients 7-14 d after initial dose to assess for response. Increase doses 2-fold over previous one for patients experiencing incomplete paralysis of target muscle. Do not exceed 25 U when giving it as single injection or 200 U as cumulative dose in 30-day period.

 

Follow-up

Further Outpatient Care

Regular office visits are useful to monitor nystagmus.

Prognosis

Prognosis is dependent upon etiology.

 

Questions & Answers