An important point of information to be gained from the fixation test is the adequacy of gaze holding, as impaired gaze holding may indicate the presence of a central (cerebellar or brainstem) lesion.
Gaze-evoked nystagmus (GEN) is a drift of the eye which is only present for certain directions of gaze away from straight ahead. It is the most common form of nystagmus encountered in clinical practice. When using EOG recordings, any persistent nystagmus for ocular displacements of 30 degrees or less is considered abnormal. When using infrared recordings, small amounts of weak (0.5 deg to 3.0 deg/sec) gaze-evoked nystagmus can be recorded in normal subjects (Abel et al, 1978).
"End point nystagmus" is a variant of GEN. It is basically GEN in persons who are otherwise normal. It is more frequently seen with prolonged gaze holding and also with large eccentricities. It is often somewhat torsional. The judgement as to whether nystagmus is called GEN or "end point", is presently one made by the experience of the examiner. We think it best to avoid the term "end point nystagmus" entirely.
Causes of gaze-evoked nystagmus are listed in the table above. There are several distinct patterns which can be identified by close scrutiny of the eye position trace. (Note that we didn't say that you can get this by reading the computerized ENG report - - commercial ENG computers don't understand GEN).
Ordinary gaze-evoked nystagmus, acquired from an ancient ENG system. There is drift towards the center when the patient looks to either side.
The most common variety of GEN consists of a drift towards the center of the orbit, interspersed by corrective outgoing saccades attempting to acquire a target which has drifted off the fovea. In this situation, it is conventionally thought that the initial rate at which the eye drifts is directly proportional to how far the eye is from center, because elastic restoring forces are proportional to displacement. Accordingly, as the eye approaches center, the rate of drift decreases, accounting for the characteristic decreasing exponential trajectory of ocular drift. The decreasing exponential pattern may be difficult to appreciate if the patient makes frequent saccades to the target, and one must look for a slow phase in which the patient allowed his eye to drift close to the center. Gaze-evoked nystagmus on lateral gaze and upward gaze is common while gaze-evoked nystagmus on downward gaze is infrequent.
Certain patients with congenital nystagmus or with acquired central nystagmus varieties have increasing exponential velocity patterns. More about this is below.
Rarely, GEN is due to weak eye muscles, such as in myasthenia gravis. As myasthenia can affect eye muscles to different extents at different times, the variations are many. A nystagmus that comes and goes, and that is asymmetrical between the eyes might be myasthenia. This type of nystagmus can change dramatically after injection of a medication that temporarily improves muscle strength (such as edrophonium). Any change is counted as a positive "tensilon test".
Amount of GEN
There are several factors which contribute to the amount of GEN. What we are really talking about, implicitly is the idea that there are several subsystems that contribute to maintenance of eye position. Each of these systems contributes force, and the net movement of the eye is related to the balance of force.
- Orbital elasticity attempts to return the eye to the center.
- Central position integrators (i.e. the step), attempt to compensate for orbital elasticity. Failure to do this is called a "leaky integrator". This results in an equation relating eye velocity to eye position.
- "touch up" integrators responsible for rebound nystagmus, that help the central position integrator.
- Tracking systems attempt to keep the eye on target (e.g. smooth pursuit) -- only present in the light. It is not thought that orbital proprioceptors contribute much to gaze nystagmus.
With respect to orbital elasticity, #1, for the most part, this is generally assumed to be constant across most individuals, although there are clearly individuals where stiffness is too high (such as in Duane's syndrome). . Roughly, force is proportional to E-E0, and thus eye acceleration = kE (where k is the spring constant of the ocular muscles).
The second force relates to neural firing designed to counteract the orbital elasticity. This is envisioned as a neural "integrator", that creates a holding force to counteract the force due to orbital elasticity. The neural integrator is the dominant part of the gaze control system as the eye muscles are very powerful compared to the forces of orbital elasticity. Using an mechanical analogiy, the integrator is like a tank that holds a fluid level proportional to eye position, but has a leak at the bottom. When the tank is full, the flow through the leak is high, when it is nearly empty, the leak doesn't do much of anything. The rate at which fluid declines in the tank, or in other words, eye velocity, is proportional to eye position. This is called the "leaky integrator" and structures in the brainstem have been found that are tentatively the localization of the neural integrator. Central disorders, particularly those involving the cerebellum are associated with greater leaks, and thus centripetal drift. This equation is formulated in terms of eye velocity, Edot, which is proportional to Eye position.
A third force, little considered, but important to understanding gaze is the "rebound" nystagmus mechanism. As a person continues to hold gaze in spite of drift back towards the center, the speed of the drift ordinarily slows down after about 10 seconds. Then when one looks back to the center, the eye drifts toward the previous location of gaze holding. This is thought to be due to a negative feedback process where a "rebound" integrator charges up, and then discharges when back to center.
A fourth force relates to how proficiently the patient can use visual tracking mechanisms such as pursuit or optokinetic responses to offset and eliminate drift, even though it is self-generated. A person can have GEN in the dark, but not in the light, if they have good tracking. This can be a very huge impact on persons with congenital nystagmus where it increases the nystagmus, but ordinarily presumably it reduces nystagmus. This system is generally very poor in persons with cerebellar disorders. . On VENG's, we don't think it is necessary to record GEN in the light, because this information is obtained in the saccade test. However, we do think it is prudent to record GEN (and rebound) in the dark.
A final factor relates to the frequency with which the patient develops corrective saccades. A person might make a huge number of small corrective saccades, or just a few big whopping saccades.
These factors are based on ideas about physiology.
Different fitting functions for GEN
Although conventionally, GEN is viewed as a consequence of orbital elasticity, with velocity proportional to eccentricity from the effect of the neural integrator and it's leakiness, (i.e. V=K*E), this single parameter framework does not capture all of the observed behavior -- nystagmus may not only vary with eccentricity, but the shape of the decay may vary as well. Or to put this into mathematical terms, one needs more free paramaters than one can get from a simple neural integrator. . In the discussion above, one might reasonably need 4 or more parameters -- more than we can usually identify.
To assist in curve fitting, Romano et al (2017), introduce a formula with more parameters, namely V=(k2/k1)*tan(k1*E). By introducing a second parameter, k2, this function can adjust both the scale with k2 (which is the same as K above), and introduces k1, which allows for a tangent shaping function. This is an expediant of these authors, with an unclear correlation to physiology.
Bottom line regarding physiology:
As developed above, there are many sources of forces that control eye position, and one must mainly consider the "neural integrator", but also think of visual tracking and the rebound process.
Because the relative contribution of these forces are normally unknown, and furthermore there is generally only an "eyeball" estimate of eye velocity , the judgment that a patient has an abnormal amount of GEN is usually a qualitative one, based on the observation that the patient has nystagmus on gaze in one direction, but none in the other, or nystagmus for unusually small displacements from center.
Medication and GEN
GEN is an extremely common consequence of medication, especially sedatives or anticonvulsants. Phenytoin, for example, can be monitored through watching for GEN. No GEN generally means that the patient is not taking his/her medication. All sedatives produce GEN.
Alcohol and recreational drugs commonly cause GEN - -Ketamine being an extreme example. (Romano et al, 2017). Phencyclidine is also characterized by nystagmus (Dominici et al, 2014), as well as hypertension and agitation.
Technical Issues regarding GEN
There are several major problems in interpreting GEN, mainly deriving from technical error.
- ENG system saturates -- this is a major problem with video ENG systems.
- Technician/Audiologist doesn't know how to test GEN -- doesn't ask patient to look to the side, or doesn't hold for long enough.
- Patient closes eyes
If your equipment doesn't record the eyes looking far to one side (i.e. saturate), you will think there is no GEN. Video ENG systems often saturate.
Another common problem is that the person testing for GEN makes one of several common errors -- they may not have the person look far enough, or not encourage them to hold gaze for 10 full seconds. They may allow the person to move their head and eyes. They may allow the person to close their eyes -- no video system can track through closed eyes. All of these errors can be difficult to catch when one is presented with a recording loaded with strange findings. The best way to catch these things is to compare the clinical exam with the recording, and in-service the person doing testing when there are discrepancies.
Asymmetric gaze-evoked nystagmus: Alexander's law -- the gaze-evoked nystagmus seen in vestibular disorders.
Video of Alexander's Law
Gaze-evoked nystagmus which is of greater when looking in one direction than the other occurs in several situations. In vestibular disorders, when gaze-evoked nystagmus is combined with a spontaneous nystagmus, they add when gazing towards the fast phase of the spontaneous nystagmus and subtract in the opposite direction. This often results in the pattern of a greater overall nystagmus when gazing towards the fast-phase direction of the spontaneous nystagmus. This common clinical pattern is called "Alexander's law" (Robinson et al, 1984), and occurs in patients with peripheral and in some patients with central vestibular imbalance.
Brun's nystagmus, which occurs in patients with cerebellar lesions, refers to asymmetrical nystagmus in which there is little or no spontaneous nystagmus in primary position, but an asymmetry exists at the extremes of lateral gaze. Baier and Dieterich (2011) recently reported a study of Brun's (see end of this page). Brun's nystagmus has very little clinical utility.
Patients with internuclear ophthalmoplegia (INO) often exhibit a discongugate gaze-evoked nystagmus in which the abducting eye exhibits a more prominent nystagmus than the adducting eye. This is noticed by watching both eyes (one usually has to look back and forth between the left and right eye).
Gaze-evoked nystagmus seen in CN (Congenital Nystagmus)
Certain patients with congenital nystagmus or with rare acquired central nystagmus varieties often have "increasing exponential" velocity patterns. Often the eyes "jump the wrong way" -- in other words, one might see right-beating nystagmus in left gaze.
These waveforms are usually easy to spot because the nystagmus is so vigorous. Persons with CN also generally have less nystagmus in the dark as well as nystagmus in central gaze. Another clue is the history of nystagmus from infancy.
There are people with mild variants of CN who are misdiagnosed as something else -- such as multiple sclerosis, or a cerebellar degeneration. This can be easily figured out with some thought -- these people don't have any neurological findings other than CN, and they don't get worse over time.
Gaze-evoked nystagmus seen in INO
Patients with a saccadic disorder called internuclear ophthalmoplegia (INO) often exhibit a discongugate GEN in which the abducting eye exhibits a more prominent amplitude nystagmus than the adducting eye. This is easily detected through the saccade test, which shows slowing of adducting saccades.
Gaze-evoked nystagmus seen in cerebellar disorders.
Patients with cerebellar disturbances often have gaze-evoked nystagmus. The common syndromes are:
- Too much gaze-evoked nystagmus considering orbital eccentricity
- Downbeating nystagmus on lateral gaze
- Rebound nystagmus
Patients with cerebellar disturbances often have more rapid drift for a given orbital eccentricity than normal subjects. This is attributed to diminished function of the neural positional integrator, thought to be maintained by the cerebellum. There are actually more possibilities than this, when one considers the problem from a physiological perspective.
Rebound nystagmus has to do with a feedback system that presumably assists in overcoming gaze evoked nystagmus, that decays away after the eye is brought back to center.
Considering downbeating nystagmus on lateral gaze. An example of this is shown below.
Downbeating nystagmus on lateral gaze. Recorded using an Micromedical Technology IR tracking system at Chicago Dizziness and Hearing.
This record was obtained in a young woman from a family with a familial cerebellar degeneration. The velocity of downbeating nystagmus increases to an astounding 33 deg/second on right lateral gaze. This pattern of DBN increased by lateral gaze suggests a cerebellar disorder, with the main suspects being paraneoplastic cerebellar degeneration, a Chiari Malformation, or other cerebellar disorder (such as was the case here). This patient also has a left-beating spontaneous nystagmus.
The movie below, from a patient with a paraneoplastic cerebellar degeneration, shows what this looks like using the video Frenzel goggles.
According to Baier and Dieterich (2011), about a third of patients with cerebellar strokes have "unidirectional" GEN. This presumably is the same nystagmus previously called "Brun's" nystagmus. This study is very difficult to interpret as the criteria for identifying GEN were omitted from the article, and there was no data concerning the prevalence of spontaneous nystagmus, which might reasonably convert a bilateral GEN into a unilateral. In our experience, "unilateral" GEN is generally associated with an inner ear disturbance.