© 1996-2004, Timothy C. Hain
This material is at a continuing medical education level.
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A typical calibration test is shown below.
Methodology of the calibration test:
The calibration test measures rapid eye movements and calibrates the eyes for the remainder of the test. Horizontal rapid eye movements are always assessed. Occasionally vertical eye movements are measured, and extremely rarely, torsional eye movements are measured. Devices that measure eye movements are discussed here.
Methodology of Eye movement Recording
|EOG||Horizontal well, Vertical poorly||Torsion|
|IR||Small horizontal very well, Vertically poorly||Torsion|
|Video ENG||Horizontal and vertical moderately well||Torsion only by inspection|
|Scleral Eye Coil||Horizonal and vertical very well||With special measures can measure torsion moderately well|
Saccadic testing is sometimes useful as cerebellar disorders and degenerative disorders of the central nervous system can sometimes be revealed through saccadic testing. While the clinical examination by an experienced examiner is the more efficient method of making these diagnosis, such expertise is not always available. The three saccadic parameters most relevant to clinicians are peak velocity, latency, and accuracy.
Disorders of Saccadic Velocity
|Table 2: Peak velocity of 20 deg saccades in normal subjects|
|METHOD||Peak Velocity||Lower limit of normal|
|Infrared (300 hz bandwidth)||657||491|
|Eye coil (60 hz bandwidth)||650||325|
|EOG (15 h bandwidth)||336||252|
Normal values for the velocity of 20 degree saccades are given in table 2. Note that velocity is very sensitive to the method by which saccades are recorded. Normal saccadic velocity values obtained via infra-red methods or scleral search coil recordings are usually higher than those obtained via EOG recordings. EOG and video methods presently predominate oculomotor recordings. These two methods have similar bandwidths and thus similar limites for normal.
Saccadic velocity is approximately proportional to saccadic amplitude for sizes between 5 and 20 degrees. After amplitude reaches 20 degrees, saccadic velocity undergoes a soft saturation with respect to further increases in amplitude. This pattern is seen on main sequences, which plot peak velocity against saccade size. The usual upper limit for saccadic velocity, no matter how big the saccade, is about 750 deg/sec. The author uses the function given in equation 1 (see below) for his limits of normal velocity. For the lower limit, the asymptote is set at 350 deg/sec. For the upper limit, the asymptote is 750 deg/sec. Saccade amplitude is designated by E and saccadic velocity, E dot. Saccadic velocity cannot be altered voluntarily and is not affected substantially by age or gender.
There are several pitfalls to be aware of in measuring saccadic velocities. Variability is appreciable and one is advised to acquire about 40 saccades varying in size between 10 and 40 degrees to develop a reasonable main sequence. Calibration error is another common problem. The calibration error may be related to subtle factors, which are not evident when the oculomotor test is read. For example, patients with ocular motor palsies are unable to get one or both eyes to the target. Patients with strabismus may alternate the eye that they view from, depending on the direction of gaze, and allow one eye to drift out away from the target. In these instances, measured saccadic velocities are wrong, because the calibration is inappropriate. Monocular recording and single eye viewing are essential to avoid error in these sorts of patients. In patients without problems of ocular alignment, evidence that the calibration is stable over several trials must be available before diagnosing abnormalities of saccades.
Causes of slow saccades
There are three types of disorders of saccadic velocity. Saccades may be too slow, too fast, or have substantially different velocities in one eye or direction than the other. Saccadic slowing is diagnosed when mean saccadic velocity for a particular amplitude is less than the lower fifth percentile of normal. Table 3lists causes of slow saccades (from Hain, 1993).
When saccadic slowing is observed, drug ingestion should be the first consideration. Anticonvulsants, sedatives and sedating antidepressants are the most common culprits. Saccades can be slowed as much as 50% when subjects become drowsy. If the patient is wide awake and not taking a centrally acting medication, then the alternative diagnoses in table 3 should be considered.
In some disorders, subtleties of the pattern of saccadic slowing will allow one to further narrow down the list of diagnostic possibilities. One should try to judge whether the slowing involves all saccades, or just horizontal or vertical saccades. Metabolic conditions, such as drug ingestion and drowsiness, cause global saccadic paresis. Most degenerative conditions of the central nervous system that are accompanied by slow saccades; such as cerebellar degenerations, Huntington's chorea, and the chronic progressive external ophthalmoplegias also cause a similar global pattern of slowing. Miller Fisher syndrome, characterized by the triad of opthalmoplegia, ataxia and areflexia is another example.
On the other hand, several disorders affect vertical saccades and horizontal saccades differentially. Disorders which affect vertical saccades to a greater extent than horizontal saccades include disorders of the midbrain, such as progressive supranuclear palsy (PSP), and the ocular muscle involvement typical of thyroid disease. ALS has also been reported to have slowed vertical saccades (Averbuch Heller et al, 1998). Another helpful point that may assist in identification of PSP and related disorders is constriction of range. For example, in figure 1B, while the target displacement was as large as 40 degrees, this patient showed a paucity of saccades greater than 30 degrees. Examples of disorders which affect horizontal saccades to a greater extent than vertical saccades include focal lesions of the pons such as internuclear ophthalmoplegia, sixth nerve palsy, and in disorders of the lateral and medial ocular muscles.
In internuclear opthalmoplegia, for horizontal movements, the adducting eye is slowed while the abducting eye typically has normal velocity and has a nystagmus. For vertical eye movements, the MLF appears to primarily carry posterior canal signals and anterior canal derived eye movements are spared (Cremer et al, 1999).
Ocular myasthenia may cause weakness of all ocular muscles, or be restricted to individual muscles. Thus, the horizontal-vertical distinction does not help in the diagnosis. Rather, the diagnosis is usually made via observation of fluctuation of ocular alignment from minute to minute, restriction of eye movement to the central range, and post-saccadic drift (see following section on post-saccadic drift for an example). Myasthenics may also develop a progressive slowing of saccades over time, due to fatigue (Spooner and Baloh, 1979). Ocular myasthenia is usually associated with ptosis and ocular findings are usually affected by small amounts of intravenous edrophonium (the "tensilon" test), but positive ocular tensilon tests have also been reported in the Eaton-Lambert syndrome (Dell'Osso et al, 1983)
Table 5: Abnormally fast saccades
Abnormally fast saccades can usually be traced to an error in calibration or a noisy eye movement recording. As an example of calibration error, consider the case when a patient makes a 5 degree saccade to a 15 degree target displacement. Then calibration factor will be three times too large, and saccades will appear to be abnormally fast. Noisy recordings, such as due to a poorly applied EOG electrode or blink artifact are another cause of what appears to be inappropriately fast saccades. Because saccadic velocity is calculated from the peak velocity, velocity noise adds to the real peak velocity, and results in incorrectly high velocities. This is particularly a problem with infra-red recordings, which combine high bandwidth with susceptibility to blink artifact.
In rare instances, abnormally fast saccades may real, and not due to a technical artifact. One cause is the opsoclonus syndrome or it's relative, ocular flutter. In these conditions, patients make unintended saccades without intersaccadic interval, which may be abnormally fast for their size (Bergenius, 1986). More about ocular flutter and opsoclonus can be found here.
A rare cause of saccades that are too fast for their size are ocular disorders in which eye movement is restricted. A large saccade may be programmed centrally, but because the eye is brought up short by muscular restriction or rapid fatigue, a small saccade is made with the velocity appropriate to a bigger saccade. A clue here is that these patients never make saccades faster than the upper limit of normal for large saccades (about 750 deg/sec for recordings made with a 40 Hz bandwidth)
Bahill AT, Brockenbrough A, Troost BT. (1981) Variability and development of a normative data base for saccadic eye movements. Invest Ophthalmol Vis Sci 21, 116-125
Baloh RW, Konrad HR, Sills AW, Honrubia V. (1975) The saccade velocity test. Neurology 25, 1071-1076
Henriksson NG, Pyykko I, Schalen L, Wennmo C. (1980) Velocity patterns of rapid eye movements. Acta Otolaryngol 89; 504-512.
Table 5: Asymmetrical saccadic velocity
Saccadic velocity, for a given amplitude, should be equal between eyes. Velocity should also be equal whether the eye is abducting or adducting. Saccadic velocity asymmetry then consists of significant inequality in velocity between eyes or directions. Of course, asymmetry between eyes can only be detected when monocular recordings are available. Unfortunately, the method by which velocity is measured can create an artifactual asymmetry. Studies done using EOG recordings suggest that adducting saccades are faster, while studies performed with infrared recordings suggest that abducting saccades are faster (9)(Becker, 1989). The difference between the peak velocities of abducting and adducting 20 degree saccades reported by Fricker and Sanders (1975)(13) in a population of 40 normals ranged from -70 to 200 deg/s (95% range, infrared method). We recommend establishing one's own fifth percentile lower limits of normal, for the method in use locally.
Table 5 lists the most frequent causes of asymmetrical velocity. There are several potential asymmetry patterns, the most common of which is normal abduction with slowed adduction. This occurs mainly in internuclear ophthalmoplegia or "INO" . INO is due to a lesion in the median longitudinal fasciculus or "MLF", which connects the paramedian pontine reticular formation and the oculomotor nucleus. The MLF is located immediately adjacent to the cerebral aqueduct. INO is most often found in patients with multiple sclerosis or cerebrovascular accidents involving the brainstem (Fischer, 1967; Wall and Wray, 1983). The hallmark of INO is slowing of adducting saccades, accompanied by an overshoot of the abducting eye. The condition can be unilateral or bilateral. A reduction of adducting velocity into the abnormal range, accompanied by normal abducting velocity, for medium size saccades (about 20 deg), should cause one to consider INO. In this case, one should also examine the position traces of each eye. The combination of an overshoot of the abducting eye, and significant slowing of the adducting eye occurring simultaneously, confirms INO.
Normal adduction with slowed abduction occurs most commonly in patients with palsies of the sixth cranial nerve. One should look for substantial slowing for a medium size saccade. Note that calibration error is common in this situation, as the patient with a sixth nerve palsy will often be unable to fixate the target with both eyes, when looking in the direction of paresis.
There are several other patterns which occur frequently in patients with cerebrovascular disease or demyelinating disease involving the brainstem. Preserved abduction in one eye, combined with slowing of all other horizontal motion in both eyes, occurs in the one-and-a-half syndrome. Reduced speed of adduction in one eye combined with reduced abduction in the other eye, occurs in conjugate gaze palsies. Slowing of all horizontal saccades, combined with normal vertical saccades occurs in bilateral pontine lesions which affect the burst cells, such as pontine hemorrhage.
Table 6: Disorders of Saccadic Latency
Saccadic latencies are calculated from the difference in time between target displacement and the onset of the first saccade towards the new target position. In the preceding chapter, several paradigms to elicit saccades were presented which differed mainly in their effects on saccadic latency. These included the random, express saccade, and anti-saccade paradigms. At this writing, of these, only the random paradigm is used clinically. In this simple procedure, the target changes position at unpredictable times, to unpredictable positions.
Representative normal values for latencies are given in table 6. Normal saccadic latencies are independent of target amplitude and are insensitive to the method used to record eye movements, but vary according to target luminance, size, contrast, whether the target is visual, auditory or both, and the predictability of the target (Leigh and Zee, 1991). Thus it is best to obtain normal values specific to one's own laboratory unless one is using commercial equipment within an environmentally controlled booth.
There are several pitfalls to consider when measuring latency. Latencies are relevant only when the timing of target motion is unpredictable -- patients may anticipate predictable targets, producing an latency that is impossibly short or even negative. Latency may also be reduced by input from nonvisual senses, such as noises associated with target displacement (Konrad et al, 1989). Saccadic latency is strongly affected by visual acuity, and delayed latencies are common in persons with cataracts or other disorders which reduce vision. Latency decreases about 15 ms per logarithmic unit of luminance above foveal threshold (Wheeless et al, 1967). Thus a bright target is essential. A small laser produces an extremely bright target which is ideal for this purpose. If one is using an light-emitting diode (LED) based stimulator such as a light bar, it may be helpful to test in dim lighting to improve contrast and minimize effects of visual acuity.
Prolonged and reduced saccadic latencies
A general prolongation of saccadic latency is an average latency greater than 400 msec. While general prolongation is associated certain disease processes as outlined in table 7, in most instances this finding has no diagnostic significance because saccadic latencies are sensitive to the mental state of the subject. Uncooperative patients may simply produce erratic or prolonged saccadic movements.
There are no disease processes that cause a general shortening of latency and accordingly this finding is always related to technical error, anticipation, or lack of cooperation. Lack of cooperation can cause the appearance of a general shortening of latency if one is testing a subject who makes large numbers of extraneous saccades, because latency is calculated from the time between target displacement and eye movement. When many extraneous movements are being made, if one occurs by chance just after target displacement, an abnormally short latency may be registered.
Asymmetrical saccadic latencies
On the other hand, asymmetry in latency between saccades into one or the other hemifield is useful clinically as it may indicate the presence of a lesion involving the superior coliculus, or parietal or occipital cortex. . What is helpful in this instance is that saccades in one direction provide a control for saccades in the opposite direction. This pattern is frequent in patients who have had cerebrovascular accidents. Patients with occipital lesions may not see targets in the blind parts of their fields, and may produce a "staircase" of searching saccades, the first of which has a prolonged latency (Troost, 1972). Patients with parietal lobe lesions have inattention to the side of their lesion, and may produce no saccade at all or make saccades with prolonged latency to that side (Meienberg, 1983). Patients with unilateral lesions of the superior colliculus may also show asymmetry of latency (Pierrot-Delseilligny et al, 1991).
Table 8: Disorders of Saccadic Accuracy
Table 8 lists causes of the four most common patterns of saccadic inaccuracy which include overshoot dysmetria, undershoot dysmetria, glissades and pulsion. These disorders are caused both by ocular disorders and central nervous system disorders.
There are several pitfalls to be aware of when considering the diagnosis of dysmetria. Blink artifact is the most troublesome because many subjects blink with every saccade, unless otherwise instructed. Blink artifact can be easily seen in figures 4 and 6 where there are brief deflections in the vertical trace, lasting about 200 msec, accompanied by synchronous deflections in the horizontal traces. Blinks contribute a technical artifact due to interactions with the EOG and infrared methods of measuring eye movements. Only the magnetic scleral eye coil technique of measuring eye movements is immune to blink artifact. EOG recordings are mainly affected in the vertical lead, but in infrared recordings, both the horizontal and vertical components are affected. When using EOG recordings, it is quite common for the direction of blink artifact to differ between each eye, or for blink artifact to be strong in one eye, and absent in the other. These problems are usually related to errors in electrode placement. Blinks are also accompanied by a small eye movement (Riggs et al, 1987), and also may interact centrally with saccades causing overshoot (Hain et al, 1986). Blink artifact is best avoided by having a vertical lead recording available, which allows one to ignore saccades with superimposed blinks, and by instructing the patient to avoid blinking during the testing. When a vertical lead is not available, such as in figures 2 and 7, it is quite difficult to be sure that a saccade of unusual configuration is truly aberrant, and one may have to fall back on direct visual inspection of the patient.
A more subtle pitfall relates to calibration error. Certain commercial electronystagmography systems calculate metrics by comparing the actual saccade displacement to the target displacement. In this situation, an incorrect calibration can cause a numerical dysmetria which is an artifact of the calibration error. This mistake can easily be detected by inspecting the eye position traces, as true dysmetria is always accompanied by corrective saccades.
In overshoot dysmetria, the initial horizontal saccade is too large and the corrective saccade occurs in the opposite direction to the target displacement. Figure 4 shows overshoot dysmetria in a patient with a cerebellar lesion.
Overshoot dysmetria is not always abnormal. In normal subjects, transient overshoot dysmetria is common in saccades directed towards primary position, in saccades less than about 10 degrees in size, and saccades made to a stimulus appearing in a novel location. Normal subjects, however, will readjust their saccades to a predictable target location and, after several refixations to the same place, stop producing overshoots. Overshoot dysmetria is abnormal when it is frequent (at least 50% of the time), of significant size (greater than 2 degrees), and when it occurs in centrifugal saccades larger than 20 degrees. While numerical criteria for overshoot are available Weber and Daroff (1971), we do not feel these are necessary, as the diagnosis is usually obvious from inspection. Enduring overshoot dysmetria is a classic sign of a cerebellar lesion (Selhorst et al, 1976; Ritchie, 1976). It can also occur in the abducting eye in internuclear ophthalmoplegia, in patients with visual field disturbances, and in the stronger eye of a habitual paretic-eye fixator.
Macro-saccadic oscillation (MSO) occurs when the overshoot dysmetria is so large that a sequence of refixations occur, each overshooting. While classically described in cerebellar syndromes, it can also occur when ocular function is suddenly changed, as for example, after edrophonium medication in an ocular myasthenic (Komiyama et al, 1999).
Komiyama A, Toda AH, Johkura K. Edrophonium-induced macrosaccadic oscillations in myasthenia gravis. Ann Neurol 1999:45:522-525
In undershoot dysmetria, the initial saccade is too small and the corrective saccade continues onward towards the target. Undershoot dysmetria does not carry the same pathologic connotation as does overshoot dysmetria as undershoot is common in normal subjects. Normal subjects will show about 1-2 degree of undershoot for 20 deg and larger target displacements (Lemij and Collewijn, 1989). Constant and significant (first saccade < 50% of target displacement) undershooting is suggestive of a basal ganglia disorder such as Parkinson's disease or progressive supranuclear palsy (PSP). Figure 5 shows an example of hypometric saccades produced by a patient with PSP. Patients with visual field deficits may also produce inaccurate saccades, but overshooting is the more common pattern as in this way a hemianoptic patient can put the target into their seeing field. Patients with poor vision, such as due to cataract, may simply be guessing as to new target location, and can produce undershoot or overshoot patterns.
The term "pulsion" is applied to vertical saccades that are pulled to the right or left, requiring a horizontal corrective saccade to fixate the target. Both upwards and downwards saccades are pulled in the same horizontal direction. Pulsion towards the side of lesion, or "ipsipulsion", occurs after infarcts in the distribution of the posterior inferior cerebellar artery (Meyer et al, 1980). Pulsion away from the side of lesion, or "contrapulsion", may occur after infarcts in the distribution of the superior cerebellar artery (Ranalli and Sharpe, 1986). Most clinical laboratories do not attempt to record pulsion.
The term "glissade" designates a saccade which does not end crisply, but rather glides to its end point. "Onward glissades" occur when the eye continues to glide in the same direction as the faster part of the saccade, and "backward" glissades occur when the eye drifts in the opposite direction as the main saccadic movement. Figure 6 illustrates backwards glissades in a patient with myasthenia gravis. Glissades occur in conditions in which the brainstem miscalculates the "pulse" of oculomotor activity needed to get the eye to new position or the "step" of innervation needed to hold the eye in place against elastic forces. Thus glissades are often said to be due to a "pulse-step mismatch". Patients having rapid changes in oculomotor function, such as ocular myasthenics are particularly prone to developing a glissadic pattern, because the amount of neural firing required to obtain a given eye position and to hold it there against elastic restoring forces is constantly varying. Myasthenics also may demonstrate a briefer drift called "quiver" (Yee et al, 1976). Quiver does not occur in Eaton-Lambert syndrome (Dell'Osso et al, 1983). Patients with cerebellar lesions may produce glissades because they are unable to adjust their pulse step ratio. Patients with internuclear ophthalmoplegia show onward prolonged glissades in the adducting eye, and briefer backward glissades in the abducting eye.
The main pitfall to consider when trying to decide if a patient has glissades is the adequacy of head stabilization. If the head is free to move and does so during a saccade, the eye-component of a combined head-eye saccade may resemble a glissade. Infra-red recordings also have a special problem as they may show a glissade-like artifact related to changes in eyelid position which accompany saccades.
Unintended saccades are covered in section on nystagmus in the ENG manual.
Spooner J, Baloh R. Eye movement fatigue in myasthenia gravis. (1979) Neurology, 29:29-33. January.