The saccade velocity test - Research

method for rapid quantitative measurement of ... usefulness of the saccade velocity test is clearly ... with bilateral monocular recordings at a time when.
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Article abstract

Scatter plots showingthe amplitudeversus velocity (maximum and average) relationshipof horizontal saccades in 25 normal subjects and four groups of patients were statistically compared. Three patients with “subclinical” medial longitudinal fasciculus syndromes had significant slowing of adducting saccades, and two of these patients had unsuspected slowing of abducting saccades (although to a lesser degree). Five patients with olivopontocerebellar degeneration and three patients with myotonic dystrophy had significant slowing of saccades in both directions. Five patients with surgically documented acoustic neuromas did not have significant slowing despite brain-stemcompression in three. It is concluded that the saccade velocity test can be a useful clinical tool in addition to its potential in clinical research.

The saccade velocity test ROBERT W. BALOH, M.D., HORST R. KONRAD, M.D., ANDREW W. SILLS, Ph.D., and VICENTE HONRUBIA, M.D.

A

method for rapid quantitative measurement of saccade amplitude, duration, and velocity was presented in the preceding report in this ’ issue.’ Preliminary results with binocular electro-oculographic recordings suggested that plotting saccade velocity versus amplitude could be a sensitive functional test of the extraocular motor system. This report gives detailed results of binocular and monocular recordings in 25 normal subjects and in four groups of patients for comparison. With this more detailed information, the usefulness of the saccade velocity test is clearly established.

Methods. Details of the recording system and tracking sequence are given in the preceding report. The standard sequence with random stepwise jumps between 3 and 36 degrees was used for all recordings. Norrriul subjec.t.7. Twenty-five normal subjects, 12 males and 13 females ranging in age from 22 to 64 years, were recruited either through a newspaper advertisement requesting paid volunteers or from volunteer technicians and physicians. A medical history and a medical examination ruled out any illnesses that might interfere From the Department of Neurology (Dr. Baloh) and the Department of Surgery, Head and Neck Division (Drs. Konrad, Sills, and Honrubia), University of California, Los Angeles. This study was supported by USPHS grant NS09823 and a grant from the Deafness Research Foundation. Received for publication April 4, 1975. Reprint requests should be addressed to Dr. Baloh at the Department of Neurology, Reed Neurological Research Center, University of California, Los Angeles, CA 90024.

with performance during the test. All subjects had at least 20130 visual acuity with correction. No drugs were taken within 48 hours before the testing session. All 25 normal subjects had binocular recordings, and 11 of the same subjects had bilateral monocular recordings at a subsequent recording session. Patients. Group A-Medial longitudinal fasciculus syndromes. Three patients with previously documented medial longitudinal fasciculus syndromes were studied with bilateral monocular recordings at a time when dissociated nystagmus was not present on examination. Two of the patients had well-documented multiple sclerosis, and the third had a previous history of basilar vertebral insufficiency followed by an acute brain-stem stroke 6 weeks before recording. The multiple sclerosis patients previously had had bilateral dissociated nystagmus, whereas the stroke patient had had dissociated nystagmus to the left only. Group B-Brain-stem degeneration. Five patients with olivopontocerebellar degeneration were studied with binocular recordings. Each patient had a slow progressive history of ataxia and spasticity along with variable brain-stem signs. Each had a full range of extraocular movement. Two had a family history of a similar disorder. Group C-Myotonic dystrophy, Three patients with classic myotonic dystrophy were tested with binocular recordings. Each had a full range of horizontal extraocular movements and no visual complaints. Group D-Acoustic neuromas. Five patients with surgically confirmed acoustic neuromas were tested before surgery with binocular recordings. Three of the tumors were large enough to produce brain-stem NEUROLOGY 25: 1071-1076,Nowmber 1975 1071

Saccade velocity test

compression (3 to 5 cm in diameter), while the other two were less than 2 cm in diameter and confined to the internal auditory canal. The three patients with large tumors had impaired slow pursuit to the side of the tumor and decreased optokinetic nystagmus when the drum rotated toward the tumor side.

Results. Norrrial sutjje(,ts. Saccade amplitude-velocity (maximum and average) plots were constructed in each subject for binocular and monocular recordings, with separate plots of saccades to the right and left. Each plot was then best fit by the exponential equation: Eye velocity =K(1- exp. [ -amplitudell]) with the two constants (K and L) being determined by a computer program using a nonlinear least-square method. (The rationale for using this equation is given in the preceding report.) Figure 1 demonstrates the amplitude-maximum velocity relationship in a normal subject recorded first with binocular electrodes and then with monocular electrodes. With binocular recordings, saccades to the left were 7 percent faster than those to the right, while with both monocular recordings, temporally directed saccades were faster than nasally directed saccades. The right eye made 12 percent faster saccades to the right, and the left eye made 4 percent faster saccades to the left. The line drawn through the scatter plots is the computer-derived best-fit curve. The constants K and L and their standard deviation as determined by the curve-fitting program are given in each case. In this

equation, K represents the maximum velocity as the curve reaches the asymptote, and L is a curvature parameter increasing in magnitude as the curvature decreases. The sum of squares is a measurement of the goodness of fit of the exponential curve to the experimental data. The sum of squares was consistently greater for monocular than for binocular recordings, reflecting greater scatter of the experimental data with monocular recordings. The corneal-retinal potential recorded with monocular electrodes averaged 23 percent less than the potential recorded in the same subject with binocular electrodes, and the resulting decreased signal-to-noise ratio probably accounts for the greater scatter in the monocular data. Figure 2 demonstrates plots of average velocity against amplitude of saccades in the subject shown in figure 1. The average velocity is approximately 60 percent of the maximum velocity in each plot. As with maximum velocity, temporally directed saccades are faster than nasally directed saccades in this normal subject. Table 1 summarizes data from similar plots in all 25 normal subjects with binocular recordings and in 1 1 of the same subjects with monocular recordings. Since there was no significant difference between results in men and women, all are grouped together. With binocular recordings, the mean of the eye velocity measurements (maximum or average) was approximately equal in both directions, while with monocular recordings it was greater to the right. None of the differences were statistically significant, however. When each of the 1 1 subjects with

DIRECTION:

-

560 -

] RIGHT

BOTH

f-. 1 f

420 280 V v) 0,

\

CF W U

I

>.

560 -

0

s

420-

W

280-

5

140-

>

BINOCULAR

K = 627 2 21.9 L=15.8?1.0 Sum sq = 14448

Sum sq =9333

1

11 //

1

Y

k

K: 584 2 0.7 14.1

K = 606 2 13.5 L=14.32.7 Sum sq = 28288

140-

] LEFT

.... .

1

..J MONOCULAR Rt.

K = 6 4 0 k 26.8 L = 16.5f1.3 S u m sq = 20209

K = 725 2 23.2 L=17.2-+1.1 Sum sq = 19516

I

rX

1

a

3 420-

-

280-

f 17.8 L: 15 8 2 0.9 Sum sq = 40750

K = 642

140-

10

20 30 4 0

L: 15.6 k 1.3 Sum sq 17515

if L

.AR

Lt.

K = 655 2 23.8 L= 15.92 1.2 Sum sq = 20156

I 10 2 0 30 4 0

10

20 30 4 0

AMPLITUDE Figure 1. Saccade amplitude-maximum velocity plots in a normal subject recorded first with binocular electrodes and then with bilateral monocular electrodes. K and L are the constants determined by a curve-fitting program and the sum of squares (Sum Sq) representsthe goodness of ?itof the exponential curve to the experimental data. 1072 NEUROLOGY November 1975

DIRECTION : BOTH

-$

fn

LEFT

RIGHT

BINOCULAR 140

373? 11.9 15.5t 1.0 17271 Sum Sq

\

K

=

t

=

-

K

=

L

=

365 i. 14.8 14.21 1.2

0

aJ

-0 v

I >=

0

9

MONOCULAR Rt.

3 2 0 ] / # 160

.;

.

'

W

>

*

K

= 458 t 33.6 L = 25.6t3.0 Sum Sq = 38421

Sum Sq

=

i = 23.1 t 4.3 Sum Sq * 19917

9374

W

c3

MONOCULAR it.

10

20

3 0 40

10

20

30 40

10

20

30 40

AMPLITUDE , Saccade amplitude-averagevelocity plots in the same normal subject as in figure 1. Recordingconditions Figure 2, identical to figure 1.

monocular recordings was evaluated individually, six made faster saccades temporally with each eye, four made faster saccades to the right with each eye, and one had faster saccades to the left with each eye. Although the mean K values for maximum velocity (K-max) were approximately double the mean K values for average velocity (K-ave), there was little difference in the L values. T h i s m e a n s t h a t the c u r v a t u r e of t h e amplitude-velocity plots was similar for both maximum and average velocity. Plotting K-max against K-ave for the 25 normal subjects gave a correlation coefficient of 0 . 9 2 ,

demonstrating the expected interdependence of these two coefficients. The correlation between K-max and L-max in the 25 normal subjects was also high (r = 0.83), suggesting interdependence between the two constants determined by the curve-fitting program. This means that if two normal subjects have a similar K value (representing the maximum velocity attained by the curve), they will have similar velocities at each amplitude along the curve (since their L value or curvature variable will be similar). Analysis of variance of all pertinent variables did not reveal any other significant findings. Table 2 provides information concerning directional

Table 1. Mean and standard deviation of K and L for binocular and monocular recordings in normal subjects

NEUROLOGY November 1975 1073

Saccade velocity test Table 2. Mean and standard deviation of right K minus left K in each normal subject

symmetry of saccade velocity in the 25 normal subjects. The K value for saccades to the left was subtracted from the K value of saccades to the right in each subject. The mean and standard deviation of these differences were then calculated. If these values are expressed as a percentage of the mean K values, the maximum acceptable difference between right-directed and left-directed saccades (95 percent confidence) for binocular recordings is 13 percent and 15 percent for maximum and average velocity, respectively. For monocular recordings, the normal percentage difference depends on the direction and eye being evaluated. When maximum velocity statistics are used, saccades to the right by the right eye can normally be as much as 26 percent faster than saccades to the left, whereas saccades to the left by the right eye will normally be only 12 percent faster than saccades to the right. With the left eye, saccades to the right can be 28 percent faster than saccades to the left, while saccades to the left can normally be 24 percent faster than saccades to the right. Puricws. Group A-Medial longitudinal fasciculus syndromes. In each patient, nasally directed saccades (by either eye) were significantly slowed, i.e., K value < normal mean - 4 SD (p < 0.01) (table 3). In addition, patients 2 and 3 had significant slowing of temporally directed saccades although to a lesser degree (p < 0.05). The differences between temporally directed and nasally directed saccades were significant ( p < 0.05) in each patient except in patient 3, right eye. Of interest, the percentage difference between temporally and nasally directed saccades was greater for average velocity than for maximum velocity. This would suggest that the maximum velocity of adducting saccades was maintained better than average velocity. Figure 3 demonstrates the abnormal amplitude-maximum velocity relationships in patient 1 . %up B-Olivopontocerebellar degeneration. Each

patient had significant slowing of saccades, whether they were directed to the right or left (table 4). The degree of slowing was equal for maximum and average velocity. There was no significant difference between saccades directed to the right or left. Figure 3 demonstrates amplitude-maximum velocity plots in patient 1 . Group C-Myotonic dystrophy: The patients with myotonic dystrophy showed the most significant slowing of saccades as a group (table 4). Patient 3, shown in figure 3, had one-third the normal maximum velocity for saccades in both directions. Average velocity and maximum velocity were approximately equally affected. Group D-Acoustic neuromas. Patients 1 , 2, 3, and 5 had left acoustic neuromas, and patient 4 had a right acouqtic neuroma. Patients 3, 4, and 5 had surgically proved brain-stem compression. All K values were within normal limits, and there was no significant asymmetry.

Discussion. Since saccade velocity cannot be voluntarily altered, any observed slowing indicates extraocular motor dysfunction.2 This can be reversible dysfunction, as in the case of reported saccade slowing with fatigue3 and intake of a l c o h 0 1 ~and ~ ~ tranquilizer^,^?^ or permanent dysfunction, as in the case of extraocular motor paresis,8 Huntington's ~ h o r e a ,and ~ brain-stem and cerebellar degeneration. Metz and associatesa reported persistent slowing of abduction saccades in the direction of a paretic lateral rectus muscle in patients clinically and electrically (electromyographically ) recovered from lateral rectus palsies. In the present report, three patients with medial longitudinal fasciculus syndromes had significant slowing of adducting saccades in both eyes despite clinical recovery. In addition, two of the three had unsuspected slowing of abducting saccades (although to a lesser degree). These data demonstrate the usefulness of the saccade velocity test in identifying subclinical extraocular motor dysfunction. Patients with brain-stem degeneration and myotonic dystrophy were also shown to have significant slowing of saccades in all directions. The degree of slowing was marked in each patient although clinically unapparent in most. On the other hand, patients with acoustic neuromas (three of whom had surgically proved brain-stem compression) had normal saccade velocity in both directions. This would suggest that intrinsic brain-stem disease (such as in group B patients) is more likely than ' O y l '

Table 3. K values from amplitude-velocity plots in Group A patients (Medial longitudinal fasciculus syndromes)

1074 NEUROLOGY November 1975

DIRECTION: 480

BOTH

RIGHT

1

360 240

120

360 240

lf' .

.

I

.I.....

*

PAT I E N T GROUP;

.

LEFT

MONOCULAR Rt.

3

.I..

K =

355f20.6 t = 10.7 f 1 7 Sum Sq = 260986

.

K '

.

43229.0 L = 10 7t0.6 Sum Sq = 13842

..... ... .. p ..: . ... K ; 356f21.4

L ; 9.5t0.9 Sum Sa

11287

A MONOCULAR Lt.

'"'

120

L

i

K -

14.6 t 1 8 234864

L

=

7.8t0.7

360t5.4 8.5t0.4 12368

L'

SumSq

Sum sq

420 1

2801f 140

A

K

=

L

=

352 ? 14.4 11.4tl.2 29548

Sum Sq

i

Figure 3. Saccade amplitude-maximum velocity plots in a patient from each group. The group A patient (medial longitudinal fasciculus syndrome) had bilateral monocular recordings, - and the BINOCULAR others had binocular recordings.

BINOCULAR

/! K

= 357 f 23.7 L 11.9t1.9 Sum Sa = 17732

346?18.0

K

10.8 ? 1. 7 = 11636

sum sq

c

c =

f

5.8 f 0.3 * 6648

Sum Sq

20+4.0

L ' 5.3i0.4 Sum Sq = 8163

560

420

140

K =

L

=

566~11.4 14.6t0.6 30203

sum sq

i

L.rrrrrrrr 10 20 30 40

f K *

555 t 17.0

L = 14.2?0.9 sum Sq = 17525

10 20 30

K

1

,

L

0 BINOCULAR

. 15.1i0.7 578?15.2

=

;m,sql=-r

10 20 30 40

AMPLITUDE

extrinsic brain-stem compression to produce saccadic slowing. A further observation of note was the grossly impaired slow pursuit to the side of the tumor in patients with brain-stem compression, despite the normal velocity saccades in the same direction. A method for quantifying slow-pursuit accuracy will be presented in a future publication. This preliminary finding, however, represents a further example of dissociated involvement of the saccadic and pursuit eye-stabilizing systems. There is confusion concerning the effect of direction on saccade velocity in normal subjects because it is necessary to compare velocity measurements made under different circumstances with different recording techniques in small groups of subjects. I 2 Several investigator^^^^^^^^ have found an increased velocity of saccades directed to the midposition compared with equal-amplitude saccades directed away from the midposition (either nasally or temporally). Other investigator^^^^^^ have reported an increased velocity of s ac ca d es d i re c t e d temporally c ompared with equal-amplitude saccades directed nasally. These two observations are not necessarily conflicting, since the latter observations were made on saccades symmetrical about the midposition (e.g., 15 degrees right to 15 degrees left, etc.). Hyde13 tested nine normal subjects with three

different-sized saccades symmetrical about the midposition (27 experiments). The saccades were equally fast for the two directions in 13 experiments, faster to the right in 11 experiments, and faster to the left in only three experiments (eye tested in each experiment was not given). In these same subjects, saccades directed to the midposition were consistently faster than those of equal amplitude directed away from the midposition. In the present report, 11 normal subjects were tested with bilateral monocular recordings in the standard saccade sequence (3 to 36 degrees amplitude saccades). Six had faster saccades temporally than nasally (e.g., figure I), four had faster saccades to the right, and one had faster saccades to the left. Therefore, normal subjects can have faster saccades in either direction by either eye. The amount of saccade velocity asymmetry in normal subjects is not large enough, however, to negate the usefulness of the saccade velocity test in identifying early extraocular motor pathology. This is clearly demonstrated by the examples given in table 3. As might be expected, binocular recordings made by averaging velocity of the two eyes demonstrate less asymmetry than do monocular recordings. Therefore, the saccade velocity test with binocular recording was used as a screening test and in those instances where diffuse pathology was suspected. NEUROLOGY November 1975 1075

Saccade velocity test Table 4.

K values from amplitude-velocity plots in Groups B, C, and D patients

When significant asymmetry was found on the binocular test or if an isolated extraocular paresis was suspected, the monocular test was used to identify the muscle involved. In addition to its use as a clihical tool, the saccade velocity test is potentially useful in clinical researchof eye movement disorders. By gathering quantitative data on a large series of patients with focal central nervous system (CNS) pathology, a better understanding of the anatomic organization of saccadic eye movements will emerge. For example, the ill-defined roles of the frontal cortex, basal ganglia, and cerebellum can be clarified. The simplicity of the test permits serial recordings giving objective measurement of disease progress. This will be particularly useful in evaluating therapy of diseases affecting the extraocular motor system. In the field of behavioral toxicology, sensitive objective tests of early CNS dysfunction are needed. Preliminary reports6 suggest that slowing of saccade velocity is an early indicator of CNS impairment from several toxins. Although measurements of reaction time and saccade accuracy were not incorporated in our preliminary analyses, such additional quantitative information can easily be obtained with slight modification of present digital programs. Pcknowkdgments The authors thank Ms. Leda Solinger and Mr. Donald Templin for technical assistance, and Drs. Lawrence Myers and George Ellison for bringing the multiple sclerosis patients to our attention,

1076 NEUROLOGY November 1975

REFERENCES 1. Ealoh RW, Sills AW, Kumley WE. et al: Quantitative measurement of

saccade ampliude, duration and velocity. Neurology (Minneap) 25:1065-1070. 1975 2. Brockhurst RJ, Lion KS: Analysis of ocular movements by means of an electrical method. Arch Ophthalmol 4631 1-314, 1951 3. Kris C: Electro-oculography. In Glasser 0 (Editor): Medical Physiology. Chicago, Year Book Medical Publishers, Inc, 1960, vol 3 4. Franck MS, Kuhlo W: Die Wirkung des Alkohols auf die raschen Blickzielbewegungen beim Menschen. Arch Psychiatr Nervenkr 213:238-245, 1970 5. Wilkinson IMS, Kime R, Purnell M: Alcohol and human eye movement. Brain 97:785-792, 1974 6. Frecker RC, Llewellyn-Thomas E: Saccadic eye movement velocity as an indicator of dose level of diazepam, pentobarbital and D-amphetaminein humans. J PharmacolExpTher, Suppl5,2:32.1974 7. Gentles W, Llewellyn-Thomas E: Effect of benzodiazepines upon saccadic eye movements in man. Clin Pharmacol Ther 12563-574, 1971 8. Metz HS, Scott AE, O'Meara DO, et al: Ocular saccades in lateral rectus palsy. Arch Ophthalmol 84:453-460, 1970 9. Starr A: A disorder of rapid eye movements in Huntington's chorea. Brain 90:545-564, 1967 10. von Noorden GK, PreziosiTJ:Eye movement recordings in neurological disorders. Arch Ophthalmol 76:l 62-171, 1966 1 1. Baloh RW, Konrad HR,Honrubia V: Vestibulo-ocular function in patients with cerebellar atrophy. Neurology (Minneap) 25:160-168, 1975 12. Fuchs AF: The saccadicsystem. In Bach-y-RitaP,CollinsCC (Editors): The Control of Eye Movements. New York, Academic Press, Inc, 1971, pp 343-362 13. Hyde J: Some characteristics of voluntary human ocular movements in the horizontal plane. Am J Ophthalmol 48%-94, 1959 14. Cook G, Stark L: The human eye-movement mechanism: Experiments, modeling and model testing. Arch Ophthalmol 79:428-436, 1968 15. Dodge R, Cline TS: The angle velocity of eye movements. Psycho1 Rev 8:145-157, 1901 16. Robinson DA: The mechanics of human saccadic eye movement. J Physiol (Lond) 174:245-264, 1964