Brain (1992), 115, 1303-1321
NEUROLOGY OF LATENT NYSTAGMUS by MICHAEL A. GRESTY, 1 TERESA METCALFE, 1 CHRISTINE TIMMS, 2 JOHN ELSTON, 4 JOHN LEE3 and CHRISTOPHER LIU 3 (From the 'MRC Human Movement and Balance Unit, National Hospital for Neurology and Neurosurgery, the department of Ophthalmology, The Hospital for Sick Children, 3Moorfields Eye Hospital, London and 4The Radcliffe Infirmary, Oxford, UK) SUMMARY
INTRODUCTION
The term latent nystagmus is used to refer to a nystagmus which appears or is markedly enhanced when one eye is covered with the uncovered eye free to view. The uncovered eye drifts off target with a slow phase movement in a nasal direction. The drift is corrected with a nystagmus beat in a temporal direction to refix the eyes on target. The eye under cover also moves with the same nystagmus waveform, although sometimes with different amplitude if it is in an extreme orbital position. Correspondence to: Michael A. Gresty, MRC Human Movement and Balance Unit, National Hospital for Neurology and Neurosurgery, Queen Square, London WC1N 3BG, UK. © Oxford University Press 1992
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We report eye movement findings in 30 patients with latent nystagmus and who were found to have a variety of associated oculomotor disorders. Latent nystagmus is defined clinically as nystagmus which appears on covering one eye and beats towards the uncovered eye. Recordings showed that the latent nystagmus in 28 patients had slow phases with linear or exponentially decreasing velocity. This nystagmus is termed 'LN'. In 13 of these patients certain manoeuvres (e.g. pursuit) provoked nystagmus with exponentially increasing slow phase velocities characteristic of the congenital form of nystagmus termed 'CN' and we propose that this is a forme fruste of CN. In two patients the nystagmus provoked by cover was latent CN. Twenty-nine patients had a history of strabismus and one had a marked phoria. Some patients had amblyopia whilst others had normal vision in each eye. Although binocular vision was usually absent, six patients had varying degrees of stereopsis. A temporonasal predominance of monocularly elicited optokinetic response previously associated with LN, was present only in a minority of patients. Some responses were bidirectionally absent or of low velocity, possibly the result of a cortical impairment of visual motion detection. The most deranged responses had slow phases which were in the opposite direction to the stimulus as described in CN. The presence of 'forme fruste' CN in many of these patients suggests that some of the derangements of optokinetic responses are due to CN. The findings indicate a greater overlap between the incidences of LN and CN than previously estimated. Thirty percent of patients had large saccadic 'square wave' intrusions. These were not present when there was marked amblyopia. They are attributed to a competitive incongruence of visual fields and eye positions. Dissociations found between the presence and severity of strabismus, stereopsis, amblyopia and optokinetic abnormalities point to these features being relatively independent although associated in typical clusterings. This is evidence against the theory that strabismus and LN are directly caused by nasotemporal optokinetic imbalance which persists because of failure to develop binocular vision. The variability of findings favours the view that LN and CN arise from a genetic or acquired embryological disorder with various degrees and directions of expression.
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M. A. GRESTY AND OTHERS
Latent nystagmus is most commonly associated with infantile or childhood onset esotropia and amblyopia. In addition, subjects with latent nystagmus are reported to have a poor monocular optokinetic response to target motion in a nasotemporal direction (Tychsen and Lisberger, 1986; Kommerell, 1988). Nasotemporal asymmetry of optokinetic nystagmus (OKN) is physiological in the neonate (Atkinson and Braddick, 1981; Naegele and Held, 1982) and it has been suggested that its persistence is the fundamental abnormality in infantile esotropia. Some subjects with LN also have 'dissociated vertical deviation' (DVD) which is an elevation and extortion of the eye under cover.
METHODS Patient selection Thirty patients were admitted to the study because examination in the clinic had revealed a nystagmus which was provoked by cover testing and which beat towards the uncovered eye. Patients who had a clearly visible, persistent, spontaneous or gaze-evoked nystagmus with both eyes viewing were excluded from the study on the basis that such nystagmus was likely to be CN. The selection included patients with very small amplitude 'manifest LN' which was markedly enhanced on cover testing and was sometimes detected on clinical examination. All patients found to have relevant neurological disease were excluded from the study. These criteria were aimed at biasing selection against including patients with obvious features likely to be CN. Eye movement recordings Eye movements in the horizontal plane were recorded from separate eyes with DC coupled electrooculography. Occasionally infrared corneal reflection oculography (bandwidth DC > 100 Hz) was used
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Latent nystagmus waveforms: LN or CN? A nystagmus that is latent may have two different types of waveform. Although they are both generically 'congenital' the two waveforms imply different kinds of mechanism (Dell'Osso et al., 1979; Dell'Osso, 1985). Accordingly, one must adopt precise criteria to distinguish between these two varieties which necessarily depend on eye movement recordings (Dell'Osso and Daroff, 1975; Dell'Osso et al., 1979). One latent type of nystagmus has a slow phase with exponentially decreasing or linear velocity in all positions of gaze; this is termed 'LN'. A second type has slow phases with exponentially increasing velocity involving a complex variety of waveforms and is termed 'CN'. (The CN type may be more familiar to the reader as the conjugate spontaneous or gaze-evoked nystagmus, often of florid appearance and present with binocular viewing.) Both LN and CN can coexist in a patient with either being the more dominant waveform or mixed in equal proportions; LN and CN with a marked latent component are illustrated in Fig. 1. The present study examined the relationships between ophthalmological and oculomotor findings in a sample of patients with latent nystagmus with emphasis on optokinetic responses because of their relevance to theories of latent nystagmus and strabismus. The findings also have implications for clinical diagnosis since latent nystagmus can be associated with a number of oculomotor abnormalities resembling disorders in acquired neurological disease. Accordingly, recognition of the characteristics of latent nystagmus may obviate extensive investigations.
NEUROLOGY OF LATENT NYSTAGMUS
1305
on children who would not tolerate electrodes. Recordings were made of eye movements in primary gaze and 30° right and left gaze with both eyes viewing and with each eye separately occluded. All but the six youngest subjects (aged 5—7 yrs) underwent vestibular testing of the horizontal vestibular ocular reflex on the motorized chair using rotational velocity steps or sinusoidal oscillation in darkness. Vestibular function will not be discussed because it is known to be normal in LN (Tychsen et al., 1985). However, vestibular responses were useful for classifying patients because they sometimes have waveforms suggestive of CN.
RESULTS
General patient characteristics Essential clinical features of the patients surveyed are given in Table 1. Twenty-eight patients had a history of strabismus beginning in childhood. When examined, 15 were convergent, eight were divergent and one alternated. Four of the patients with childhood strabismus had straight eyes following surgery or patching. Two patients had no history of strabismus but were noted to have phorias (in phoria the eyes are normally orthotropic but immediately drift into misalignment when covered). Four patients had gross binocular vision (BV) at 400' to 800' arc and one had good stereopsis at 70' of arc (measured by synoptophore or on Stereo Optical Company Inc., Stereo Test). This latter patient also had CN-type nystagmus in the far right lateral gaze which had been undetected in the initial clinical selection. Unfortunately, BV was not assessed in the two patients without strabismus. However, rapid return to orthotropia on removing cover indicates that they had some useful BV. Thirteen patients had a amblyopic eye in which visual acuity was equal to or less than 6/18. However, 10 had acuities in both eyes equal to or better than 6/9. Dissociated vertical divergence was present in 12 patients of whom nine had been operated on to correct the strabismus. In all, 13 patients had received surgery on the extra-ocular muscles. Two had botuljnum toxin injections. Patients 4 and 5 were sisters and patients 28 and 29 were mother and daughter. A further five patients had a family history of strabismus. Symptoms. Although not commonly appreciated, latent nystagmus may be symptomatic.
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Optokinetic and pursuit stimuli Pursuit and optokinetic responses were tested on all subjects with both eyes viewing and with each eye separately occluded. Pursuit stimuli comprised a red laser dot target moving over a plain blue background with a sinusoidal trajectory at frequencies variable from 0.1 Hz to 0.8 Hz with a peak amplitude of 20°. Optokinetic testing was aimed at determining how responses were related to stimulus velocity and also to position of the eyes in the field of gaze after the methods of Halmagyi et al. (1980) and Kommerell and Mehdorn (1982). Optokinetic stimuli were delivered with a 2 m diameter, whole field rotating drum with an illuminated inner surface of black and white vertical stripes, each subtending 10°. The subject was seated in the centre of the drum with head restrained. The procedure consisted of accelerating the drum at 10 deg/s2 from rest up to 80 deg/s. The acceleration was interrupted at 20, 40, 60 and 80 deg/s so that the drum rotated at constant velocity at these speeds. During constant velocity stimuli the subject was instructed to look at the portion of the drum which was straight in front and also to look at the drum with his eyes deviated over to the right and to the left by about 25—30°. After the 80 deg/s stimulus the drum decelerated to rest. To plot the graphs shown in Fig. 5, slow phase eye movement velocity was measured by aligning a protractor radius with the linear slow phases and measuring the inclination. Averages of the velocities of each slow phase occurring during a 4 s interval taken when the eyes were in the required field of gaze were calculated.
R6/6 L6/6 R6/36 L6/5
R6/5 L6/5
R6/I8 L6/4
R6/12 L6/18 BEO 6/6 R6/9 L6/9 pi BEO 6/9
6 M 33
8 M 44
9 M 13
10 F 2 I
RCS accommodative
R. exophoria
LCS
16 M 38
R6/6 L6/6
RDS
ADS
RCS DVD RDS
RCS
R6/I2 L6/6 R6/6 L6/6
14 M 5
15 M 38
LCS DVD
LCS
R6/9 L6/I8
LDS DVD
13 M 10
ACS
LCS DVD
LDS (minimal)
RDS
R6/12 p) L6/9 BEO 6/5
LCS DVD
?
RCS
?No strabismus—marked esophoria
RCS
Childhood 'squint'
LCS
LCS L/R DVD
12 M 16
II F 15
7 M7
R6/6 L6/24 + BEO6/5
5 F II
ACS
RDS DVD
7
R6/I8 L6/24 BEO6/5
RCS
LCS
R6/I2 L6/I8 R6/I8 L6/9
Present diagnosis RCS DVD
RCS
Original diagnosis
R6/9 L6/9
Acuities diagnosis
4 F 13
3 M 27
2 M 6
Patient no. Isex and age (yrs) 1 F9
TABLE 1. PATIENT
Surgery
Surgery X 1 Glasses
Surgery X4
Glasses
Surgery XI Patching, glasses
Surgery x I Glasses
Patching
R patch Surgery X2 Glasses
R patch
Glasses
Surgery X2
Treatment
Other history
Hyperactive, learning problems
'Qumsy child'
L ptosis
Speech therapy OpBoclonus?
Anxiety complex
Mild cerebellar syndrome? Patients 4 and 5 are sisters
Paroxysmal head shaking somatic tics, epilepsy
CLASSIFICATION Downloaded from by guest on February 14, 2015
CN
?
+
CN?
400'
BV?
O H X PI 73
Z D
m
73
2 > a
R679 L6/24
R6/I2 L679
R3/60 L6/24 BEO 6/9
R6/6 L676
R6/6 L6/6
R6/9 L6/18
R6/6 L6/5 R6/6 L6/6
21 M 25
22 F 6
23 M 67
24 M 19
25 F 20
26 F 35
27 F 2 4
R6/9 L6V12
30 M 42
LCS DVD
ACS nystagmus head nodding CS
LCS
Straight
CS L/ACS
Looks straight DVD
Surgery X2
Surgery X 2
R patch
Enhanced spontaneously
Patients 28 and 29 are mother and daughter*""
(Enhanced by accident)
(Enhanced by accident)
CN
+++
400'
—
-
7
-
70'
-
400'
-
ADS
Albinism'"
••*•»
*•
4007800' Botox
Surgery Glasses
Surgery
Surgery Glasses
Surgery Glasses
RDS
No history of strabismus, eyes straight with mild phoria CS Looks straight
?Exotropa
LCS
? RC-DS
LCS DVD
ACS
RCS DVD
LCS DVD
ACS
•Sister with strabismus without LN, "daughter with strabismus without LN, •"brother with strabismus and albinism without LN, ••••second daughter with strabismus without LN, " " • m o t h e r and sister with strabismus without LN Binocular vision assessed on Titmus fly test and synoptophore. 'Botox' signifies that patients had received botulmum toxin for correction of strabismus. The presence of CN in patients' eye recordings was quantified in rank order by awarding a + for each manoeuvre which provoked a CN waveform. The manoeuvres included were: cover testing of right and left eye, gaze holding to the right and left, pursuit under monocular and binocular conditions, optokinetic responses in primary and to right and left gaze nnd monocular and binocular responses considered as separate conditions and vestibular evoked nystagmus. Possible CN waveforms were ascribed a ?. Binocular vision is rated in minutes or arc or - indicates no BV. RCS «• right convergent strabismus; LCS £> ^ v
H
m
-)
r
""
O
f" O •
nasotemporal asymmetry of OKN, commonly said to be typical in LN, was seen in only four patients of whom one (patient 22) had partially expressed oculocutaneous albinism. The directional asymmetries which can be more than 20 deg/s are not a simple summation of LN with the OKN and an additional explanation must be sought. Figure 5B shows the responses of subject whose raw data records are given in Fig. 4. With monocular viewing there is a velocity saturation of nystagmus slow phase at about 20—30 deg/s rightwards and leftwards and the direction of the slow phase is inverted with respect to the stimulus direction if the eyes are deviated in the direction of drum rotation. Binocularly there is still velocity saturation which are below normal, to the right at 30 deg/s and to the left at 20 deg/s with reversal of nystagmus direction when the eyes are deviated to the left. Figure 5c shows responses whose velocities with binocular and right eye viewing
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Reversion
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NEUROLOGY OF LATENT NYSTAGMUS
OKSR
Reversal
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LE (covered)
1 s
FIG. 4. A, optokinetic responses to rightwards (OKS R) and leftwards (OKS L) stimuli which invert in direction as a function of position of the eyes. With right eye (RE) covered the nystagmus generated when the eyes are in the left field of gaze is in the opposite direction to stimulus motion. With left eye (LE) covered the nystagmus when the eyes are in the right field of gaze is in the opposite direction to stimulus motion. Although the most part of nystagmus has linear or exponentially decreasing waveforms that seen during reversal of direction on lateral gaze is suggestive of CN. B, magnified example of the nystagmus with slow phase in the opposite direction to the stimulus motion in response in high velocity optokinetic stimuli. With the eyes in the right field of gaze the nystagmus has a CN-type waveform. The tracings are for patient 6.
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M. A. GRESTY AND OTHERS C
Response velocity
80 60 40 20
Stimulus velocity
0 -20
-80 - 8 0 - 6 0 - 4 0 -20 0
B
20 40 60 80
Response velocity
80
20 40 60 80
Response velocity Binocular viewing
40
40
20
20..--
Stimulus velocity
0
0>
-40
^40
-60
-60
0
20 40 60 80
80
-80 -80 -60 -40 -20 0 80 60
60
20 40 60 80 Right eye viewing
40
40
20
20
Stimulus velocity
0
0'
-20
-20
-40
^40
-60
-60
0
20 40 60 80
80
-80 _80 -60 -40 -20 0 80
60
60
40
40
20
20
0 tr -20 -40
0
-60
-80 -80 -60 -10 -20 0
20 40 60 80
-20 -40 -60 -80 _80 -60 -10 -20 0
20 40 60 80 Left eye viewing
Stimulus velocity
20 40 60 80
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-20
-20 - _ . .
-80 -80-60-40-20
D 80 60
60
-80 -80-60-^40-20
-60 -80 -80 -60 -40 -20 0
NEUROLOGY OF LATENT NYSTAGMUS
1313
exceeded stimulus velocity for leftwards stimuli up to a saturation at 60 deg/s. Responses for nasal wards stimuli were absent on monocular viewing. Figure 5D shows responses to optokinetic stimuli which consist of a persistent right beating nystagmus with low slow phase velocities under almost all testing conditions. This subject had a marked right beating LN with no evidence of CN so one might have thought that any leftwards optokinetic response would be enhanced with the nystagmus. This was not the case which raised doubt as to whether there is any response in this direction. The uniformity of the nystagmus during optokinetic stimuli suggests that it might be an instability, triggered off in some way by the stimulus. Vertical optokinetic in latent nystagmus On clinical examination using a hand-held target or drum, most patients had apparently normal or near normal vertical optokinetic and pursuit responses both with monocular and binocular viewing, despite marked horizontal abnormalities. This finding demonstrates the independence of the horizontal and vertical systems. Several patients had sluggish responses, particularly during monocular stimulation, but in the absence of quantification their significance is uncertain. These sluggish responses were not systematically associated with DVD as one might expect. Of note, vertical optokinetic responses could appear normal with monocular stimuli presented to a severely amblyopic (6/18 — 36) eye.
Presence of 'forme fruste' of CN-type nystagmus Fifteen patients whose LN had linear or exponentially decreasing waveforms were found to have CN-type nystagmus waveforms during certain manoeuvres, in particular during pursuit and optokinetic stimulation. For example, in Fig. 4, when the eyes are in the right field of gaze, the nystagmus slow phase is in the opposite direction to the motion of the optokinetic drum and has a complex waveform similar to CN. This waveform is not the result of an interaction between gaze-evoked nystagmus and an optokinetic response since it does not occur in all circumstances when the two are opposed in direction but is specific to certain eye positions. In the context of clinical diagnosis a spontaneous nystagmus with this waveform would normally be taken as evidence for CN (Gresty et ai, 1984; Kelly et ai, 1989) and therefore we propose that this is a 'forme fruste' of CN. The extent to which CN waveforms were evident in a subjects
FIG. 5A,B,C,D. Plots of slow phase eye velocity as a function of stimulus velocity for various subjects with the eyes in centre, right and left gaze and with binocular or monocular viewing. The vertical lines on plot A are the ± I SD limits of normal performance according to our laboratory standards. Rightwards direction is positive, A and c: , binocular; ,righteye; , left eye. B and D: , look centre; , look right; , look left. Tracings are for patient 28 (A), patient 6 (B), patient 9 (c) and patient 23 (D).
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Pursuit responses Pursuit response abnormalities were similar to OKN abnormalities and there was no evidence of dissociation between optokinetic and pursuit performance in the form of robust pursuit and deranged OKN. In some patients optokinetic responses were better formed than pursuit, probably because the larger target is a stronger stimulus. Of note, pursuit was particularly provocative of saccadic square wave intrusions (Fig. 6).
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M. A. GRESTY AND OTHERS i—i—i—i—i—i—i—i
i
i
r
Saccadic instabilities.
i
i i i—rn—i—i
LE (covered) FIG. 6. Pursuit responses to a sinusoidal target (patient 9). Square-wave saccadic intrusions can be during either leftwards or rightwards pursuit with monocular or binocular viewing, consistently taking the eyes towards the left. Note slow phases opposite to target motion with left eye (LE) following leftwards and the right eye (RE) following rightwards.
eye movements is shown in the tables for direct comparison with the incidence of other features. Ten patients had CN which was provoked consistently by certain manoeuvres and a further five had occasional brief episodes of CN. Saccade abnormalities: saccadic square-wave intrusions Eleven patients had involuntary saccades or series of saccades which took the eyes away from the location of the target which the subject was required to fixate or pursue and then returned the eyes back on target giving an overall shape of 'square-wave
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HI
NEUROLOGY OF LATENT NYSTAGMUS
1315
intrusions' (Fig. 6). If subjects failed to suppress these movements after encouragement and practice to stay 'on target' and episodes occurred frequently, their saccadic control was judged to be abnormal. The amplitudes of the square waves could be as high as 20° and occurred with monocular or binocular viewing. Pursuit was particularly provocative of square-wave intrusions (Fig. 6). Relationships between LN, CN, amblyopia, OKN and square-wave intrusions The strength of associations between the various features accompanying LN is relevant to establishing those which always occur together and may be causally related. Since the 'strength' of appearance of certain features was highly variable and difficult to measure as a magnitude, these features were rank ordered according to the criteria given in Table 2
TABLE 2 DERANGEMENT OF OPTOKINETIC RESPONSES IN LN AND RELATIONSHIP WITH CN, AMBLYOPIA AND SACCADIC INSTABILITY Binocular R L
CN waveform
_+?
Amblyopia ? 6/18+
+-7 +
R+L R+L L
+
+ + + +
Square waves
77 R+L R
+ +
_+? +
+ +
+
17 F 6
±
±
+ +
+ +
+ + + ? + + + + + +
2M6
+
+
12 M 16 3 M 27 8M44 6 M 33 25 F 20 I0F2I
+ + + + + +
+ + + + + +
+ + + + + + + +
+ +
??
+
+
+ +
++++ ? +
+ + +
+
4 F 13* 20 F 10 24 M 19 15M38 5 F 11* 7M7 16 M 38 18 F 6 23 M 67 9M13 30M42
+ +
+ +
+
+ + + + + + + + + + + + +? + + + ? + + + + ++ ++ +
+ +
+ +
+ +
L
R+L ?
++++ +++++
+
R+L R+L
R R+L
+ indicates the presence of definite abnormality. ? indicates abnormality suspected or intermittently present. Optokinetic abnormalities are shown for binocular and monocular viewing with drum motion to the left (L), andright(R). Derangements of response include slow phase of nystagmus in the opposite direction to stimulus motion or lack of modulation of the slow phase velocity of the nystagmus response by changes in the stimulus velocity (this criterion includes, e.g. persistent low velocity nystagmus in response to all stimuli or very high velocity nystagmus provoked by the slightest movement of the drum. Optokinetic abnormalities underlined conform to the primitive pattern of temperonasal > nasotemporal asymmetry. Saccadic square-wave intrusions are shown by their predominant rightwards, leftwards directionality.
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Patient no. I sex and age (yrs) 21 M 25 28 F 4 2 22 F 6 1 F 9* 29 F 11 26 F 35 11 F 15 27 F 24 19F41 13 M 10 14 M 5
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M. A. GRESTY AND OTHERS
DISCUSSION
Theories of the origin of LN Some theories of LN (e.g. Tychsen and Lisberger, 1986; Kommerell, 1988) propose that strabismus and LN are a consequence of the normal physiological temperonasal > nasotemporal preponderance of optokinetic following seen in the neonate before the development of binocular vision (Atkinson and Braddick, 1981; Naegele and Held, 1982). If binocular vision fails to develop, each eye experiences a persistent nasalwards tonus via the asymmetrical optokinetic stimulation which eventually results in convergent strabismus. When one eye is viewing, the tonus is unopposed and becomes manifest as the slow phase of LN. As an additional factor there may be a cortical impairment of temporally directed motion detection (Norcia et al., 1991). This theory accepts a basic (genetic) defect, originally postulated by Worth in 1908 as 'congenital absence of the fusion faculty', but emphasizes ontogenetic factors in the evolution of the various features as a Chevasse's theory of 1939 'structural development on one hand and the rewards of use on the other' {see Lyle, 1950). A different kind of theory which specifically addresses the mechanism of the nystagmus proposes that LN arises due to problems with egocentric direction, visual field direction and the positions of the eyes (Dell'Osso et al., 1979; Abadi, 1980; Dell'Osso and Daroff, 1981). Dell'Osso's explanation is the more specific: normally a target is perceived as 'straight ahead', although there is a net vergence between the two eyes. Upon covering one eye the vergence becomes apparent in that the target is displaced nasalwards with respect to the seeing eye although it is still egocentrically in the same place. In LN these relationships are misinterpreted. When one eye is covered, an inappropriate
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to establish as scale of how much they were in evidence. This scale is shown in Table 2 by the number of plus signs ascribed to a feature. For non-parametric statistical analysis each plus sign was given the value 1. A question mark was assigned the value 0.5. Amblyopia was assigned 0 if acuity was more than 6/18 and 1 if less than 6/18. Square waves were awarded 1 for each right or left direction in which they presented, 0 if absent. On Spearman rank correlation there was a positive and significant correlation between severity of OKN abnormalities and the presence of CN-type waveforms; r = 0.46; P = 0.005 which was attained both with and without the inclusion of the two subjects who had CN on lateral gaze. However, it should be stressed that despite this group association, at least four patients with no evidence of CN in their eye movement recordings had deranged optokinetic responses for all or most viewing conditions. Optokinetic abnormalities were unrelated to the presence of severe amblyopia, Mann-Whitney U test, U = 88.8; P = 0.8 or to the presence of square-wave intrusions, Kruskal Wallace ANOVAR by ranks, H(2) = 0.016; P = 0.99. On the Mann-Whitney U test the presence of CN-type waveforms was unrelated to amblyopia, U = 68.5; P = 0.24 or to the presence of square-wave intrusions; U = 78; P = 0.57. The presence of a marked amblyopia (11 patients) and the occurrence of square-wave intrusions (11 patients) tended to be mutually exclusive, Mann-Whitney U test, U = 49; P = 0.04. Only one patient had both.
NEUROLOGY OF LATENT NYSTAGMUS
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Nature of OKN responses The optokinetic disorders in LN are more complex than hitherto described. In particular, as shown in Table 2, nasotemporal asymmetry which has been associated with LN (Kommerell and Mehdorn, 1982; Tychsen et al., 1985; Hatayama et al., 1986; Tychsen and Lisberger, 1986) is not the norm. In the simplest case the optokinetic response is totally absent or has a normal configuration but only achieves low velocity. In these cases a high velocity spontaneous nystagmus was not present, so there was adequate retinal stimulation and opportunity to observe responsivity over a wide range of velocities. This means that a well-formed but low velocity response suggests a direct impairment of optokinetic performance. It has been proposed that this is the result of an impaired velocity signal in visuo-parietal cortex (Norcia et al., 1991). For example, a poor response to a temporally directed stimulus to the right eye could be ascribed to a lesion affecting the velocity input from temporal retina to the right visuo-parietal cortex. This hypothesis awaits psychophysical testing but is corroborated by preliminary studies on movement evoked visual evoked potentials (Norcia et al, 1991). In some patients the onset of an optokinetic stimulus triggered a nystagmus which thereafter was not modulated by the velocity or direction of the stimulus. Such nystagmus
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nasalwards tonus is exerted on the eyes (with respect to the seeing eye) which causes nystagmus. Evidence against strabismus and LN being caused by optokinetic asymmetry is the number of dissociations and lack of consistent proportional relationships between these features. The optokinetic responses in LN can vary from being normal to apparently absent or 'inverted'. Although all patients with LN have strabismus or unstable phoria (Dell'Osso et al., 1979, 1983Z?) some manage their phorias well (patient 6 who only had LN and strabismus on vergence). Failure of BV is also not a necessary condition for LN since a rare patient with strabismus can have BV (patient 25) and subjects with unstable phoria have useful BV as shown by their rapid recovery of orthotropia when cover is removed. Some of our subjects with LN had familial strabismus with parent and siblings without nystagmus (Table 1). Our findings favour an alternative theory to optokinetic asymmetry as a cause of LN. It is well known that strabismus and CN can be familial and eight of our patients had parent and siblings with strabismus, both with and without nystagmus. This strong element of inheritance together with the dissociations to be found between the various oculomotor abnormalities in LN are in favour of them being variable genetic expressions as proposed by Jung and Komhuber (1964). In addition, some cases may be due to acquired embryological disorders involving mechanisms similar to inherited disorders. If problems with egocentric direction are the specific mechanism of LN, one might expect that possible confusion between eye, target and egocentric direction to be minimal with far targets and enhanced with near targets requiring greater vergence. In support of this notion it is of note that the LN in patients 6 could only be provoked when there was some degree of vergence. Incidentally, there appear to be no studies of the intensity of LN with respect to various target distances and positions of the eyes in the orbit to provide evidence for a more detailed theory of LN. An analogous mechanism is proposed for saccadic instabilities as discussed below.
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M. A. GRESTY AND OTHERS
Relationship between mechanisms of LN and CN and optokinetic responses Patients with pure LN do not have evidence of derangement of brainstem oculomotor mechanisms. Saccades and the vestibular-ocular reflex (Tychsen et al., 1985) are intact. Many patients have bidirectionally normal pursuit and OKN responses under certain conditions, i.e. with either both eyes or one eye viewing (Tychsen and Lisberger, 1986 and this study). This negative evidence suggests that the disorder underlying LN is at a cortical level. In contrast, it is proposed that CN is caused by positive feedback on the neural velocity-position integrator in the brainstem causing the eyes to drift off target with an increasing velocity (Dell'Osso and Daroff, 1981; Optican and Zee, 1984). Dell'Osso (1985) estimates that 80% of the nystagmus associated with strabismus is CN, pure LN accounts for 15% with mixtures of the two comprising only 5%. Our sample was biased against CN and so probably corresponds to the categories LN and LN+CN (i.e. 20%). Since more than 50% of our patients were found to have CN features (identified in a wider range of manoeuvres than used in other surveys), possibly up to half of the patients with LN also have some CN. The strong association between LN and CN could be taken to indicate that their underlying genetic or acquired embryological disorders are similar but manifesting in different ways according to expression factors. This view would point to a more unified theory of the aetiology of 'congenital nystagmuses'. Precisely how the mechanisms of LN and CN interact when both are present is difficult
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may be a system instability provoked by the moving visual field as suggested by Dickinson and Abadi (1990). The underlying optokinetic response may be weakly intact but is masked or even adapted out (Dickinson and Abadi, 1990). Amongst the more striking abnormalities were nystagmic responses whose slow phase directions were dependent upon the position of the eyes in the field of gaze (e.g. Fig. 4). This type of 'reversed' or 'wrong way' response was observed by Tychsen and Lisberger (1986) during pursuit tasks. These authors associated the phenomenon with low velocity target motion which was not always the case with our patients. In extreme cases the slow phases were of higher velocity than the stimuli (either in the same or opposite directions). Occasionally responses could oscillate in direction, apparently as a function of stimulus velocity (Figs 3,4). Such abnormalities are similar to those in fully developed CN (Halmagyi et ai, 1980). In CN, pursuit (Dell'Osso, 1986; Kurzan and Buttner, 1989) and optokinetic signals (Kurzan and Buttner, 1989) may be intact but are masked by, or adapted in, the presence of the nystagmus. The result is that they may have velocities which are abnormally high or 'inverted' depending upon how the stimulus affects the null point of the nystagmus. Although the more deranged optokinetic responses tended to occur when there was also congenital type nystagmus (Table 2), occasional patients with no evidence of CN-type waveforms in their recordings had marked derangements (e.g. Figs 2, 3; patient 13). One must conclude that responses with slow phase velocities greater than the stimulus or apparently inverted in direction are likely to be related to CN mechanisms even when an explicit CN waveform is not evident. In summary, there are two likely mechanisms for abnormal optokinetic responses in subjects with LN: (i) degradation of visual motion signals in the cortex; (ii) masking of the optokinetic response with the mechanisms of both LN and CN.
NEUROLOGY OF LATENT NYSTAGMUS
1319
to ascertain. In some cases the CN only appears when there is a strong velocity signal, such as pursuit, which displaces the null sufficiently to reveal the CN. When CN appears on cover testing the nasalwards drift caused by the LN mechanism might trigger the CN instability. Difficulties of interpretation arise because CN itself can have apparently linear, velocity increasing or decreasing slow phases which make proportional classification into LN versus CN hazardous (Dell'Osso, 1985).
Implications for clinical neurology Patients with latent nystagmus may show oculomotor disorders with a similar appearance to those seen in acquired neurological disease. However, if the cardinal components of LN, CN and strabismus or unstable phoria are identified, then one can recognize the various other disorders as attendant features which do not imply the presence of an acquired disorder. Accordingly, it is always of value to examine for LN in any patient who is suspected of having an eye movement disorder. Unfortunately, the interpretation of eye movements in the rare patient who may have LN and an acquired oculomotor disorder may be difficult. The amplitude of LN and CN may change throughout life (van Weerden and Houtman, 1984; Gresty et al., 1991, three patients studied here), enhancing spontaneously or with trivial disease and minor head injury. Under these circumstances it can become symptomatic and is particularly suggestive of an acquired disease. Identifying the nystagmus as LN or CN may help to obviate extensive investigations. ACKNOWLEDGEMENTS The authors wish to thank the two referees who reviewed this paper for their valuable, constructive criticism during the editorial process.
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Saccadic square-wave intrusions Subjects with strabismus are known to switch between eyes when viewing to the right and left (Dell'Osso et al., 1983a). This results in a saccade which brings the eye selected for viewing into alignment which can be construed as a convenient manoeuvre. We have shown that saccadic instabilities also occur monocularly with the patient trying to remain on target so that nothing is to be gained by switching eyes. There are two alternative explanations. First, because saccadic intrusions did not occur with severe amblyopia, it would appear that two functioning visual fields are necessary to cause the instability. The saccades could be due to the uncertainty about whether to control eye movements with respect to the visual map of the right eye or the left eye. If the maps have an abnormal correspondence with each other and with the positions of the eyes, a shift of control between maps may result in an eye movement. This mechanism is analogous to that hypothesized by Dell'Osso for LN. (ii) Alternatively, although square waves occur in normal subjects and in a variety of diseases (Jones et al., 1983; Abel etal., 1984; Shallo-Hoffmann etal., 1988), those in our patients are most like descriptions of the 'visual grasp reflex' (Sharpe, 1986) and square waves in patients with cortical lesions (Page et al., 1984). Since saccadic instability is a sign of frontal lobe dysfunction (Guitton et al., 1985), the question is raised of whether there is other evidence for frontal lobe abnormalities in these patients.
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ABADI RV (1980) Pattern contrast thresholds in latent nystagmus. Ada Ophthalmologica, 58, 210-220. ABEL LA, TRACCIS S, DELL'OSSO LF, DAROFF RB, TROOST BT (1984) Square wave oscillation: the
relationship of saccadic intrusions and oscillations. Neuro-ophthalmology, 4, 21—25. ATKINSON J, BRADDICK O (1981) Development of optokinetic nystagmus in infants: an indicator of cortical binocularity? In: Eye Movements: Cognition and Visual Perception. Edited by D. F. Fisher, R. A. Monty and J. W. Senders. Hillsdale, NJ: Lawrence Erlbaum, pp. 5 3 - 6 4 . CHEVASSE FB (1939) Worths Squint. Philadelphia: Blakiston Sons and Company. DELL'OSSO LF (1985) Congenital, latent and manifest latent nystagmus—similarities, differences and relation to strabismus. Japanese Journal of Ophthalmology, 29, 351 —368. DELL'OSSO LF (1986) Evaluation of smooth pursuit in the presence of congenital nystagmus. Neuro-
ophthalmology, 6, 383-406. DELL'OSSO LF, DAROFF RB (1975) Congenital nystagmus waveforms and foveation strategy. Documenta
Ophthalmologica, 39, 155-182. DELL'OSSO LF, DAROFF RB (1981) Clinical disorders of ocular movement. In: Models of Oculomotor Behavior and Control. Edited by B. L. Zuber. Boca Raton, FL: CRC Press, pp. 233-256. DELL'OSSO LF, SCHMIDT D, DAROFF RB (1979) Latent, manifest latent, and congenital nystagmus. Archives
of Ophthalmology, 97, 1877-1885. DELL'OSSO LF, ELLENBERGER C, ABEL LA, FLYNN JT (1983a) The nystagmus blockage syndrome.
Congenital nystagmus, manifest latent nystagmus, or both? Investigative Ophthalmology and Visual
Science, 1A, 1580-1587.
GRESTY MA, BRONSTEIN AM, PAGE NG, RUDGE P (1991) Congenital-type nystagmus emerging in later
life. Neurology, Cleveland, 41, 653-656. GUITTON D, BUCHTEL HA, DOUGLAS RM (1985) Frontal lobe lesions in man cause difficulties in suppressing reflexive glances and in generating goal-directed saccades. Experimental Brain Research, 58, 455 —472. HALMAGYI GM, GRESTY MA, LEECH J (1980) Reversed optokinetic nystagmus (OKN): mechanism and clinical significance. Annals of Neurology, 7, 429—435. HATAYAMA R, SASANO Y, KAWSAI K, MATSUZAKI H (1986) A study of latent nystagmus by the electro-
oculogram—fixation, pursuit eye movement, optokinetic nystagmus. Journal of Ophthalmology of Japan, 90, 542-549. JONES A, FRIEDLAND RP, KOSS B, STARK L, THOMPKINS-OBER BA (1983) Saccadic intrusions in Alzheimer-
type dementia. Journal of Neurology, 229, 189-194. JUNG R, KORNHUBER HH (1964) Results of electronystagmography in man: the value of optokinetic, vestibular, and spontaneous nystagmus for neurologic diagnosis and research. In: The Oculomotor System. Edited by M. B. Bender. New York: Harper and Row, pp. 428-482. KELLY BJ, ROSENBERG ML, ZEE DS, OPTICAN LM (1989) Unilateral pursuit-induced congenital nystagmus.
Neurology, Cleveland, 39, 414-416. KOMMERELL G (1988) Ocular motor phenomena in infantile strabismus. In: Physiological Aspects of Clinical Neuro-Ophthalmology. Edited by C. Kennard and F. Clifford Rose. London: Chapman and Hall, pp. 357-375. KOMMERELL G, MEHDORN E (1982) Is an optokinetic defect the cause of congenital and latent nystagmus? In: Functional Basis of Ocular Motility Disorders. Edited by G. Lennerstrand, D. S. Zee and E. L. Keller. Oxford: Pergamon Press, pp. 159-167. KURZAN R, BuTTNER U (1989) Smooth pursuit mechanisms in congenital nystagmus. Neuro-ophthalmology, 9, 313-325. LYLE TK (1950) Accommodational and other squints primarily related to the state of the refraction. In: Worth and Chavasse 's Squint: The Binocular Reflexes and the Treatment of Strabismus. Eighth edition. Edited by T. K. Lyle. London: Balliere, Tindall and Cox, pp. 125-146.
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DELL'OSSO LF, TRACCIS S, ABEL LA (19836) Strabismus—a necessary condition for latent and manifest latent nystagmus. Neuro-ophthalmology, 3, 247—257. DiCKJNSON CM, ABADI R (1990) Pursuit and optokinetic responses in latent/manifest latent nystagmus. Investigative Ophthalmology and Visual Science, 31, 1599—1614. GRESTY M, PAGE N, BARRATT H (1984) The differential diagnosis of congenital nystagmus. Journal of Neurology, Neurosurgery, and Psychiatry, 47, 936—942.
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NAEGELE JR, HELD R (1982) The postnatal development of monocular optokinetic nystagmus in infants.
Vision Research, 22, 341-346. NORCIA AM, GARCIA H, HUMPHREY R, HOLMUS A, HAMER RD, OREL-BIXLER D (1991) Anomalous motion
VEPs in infants and in infantile esotropia. Investigative Ophthalmology and Visual Science, 32, 436-439. OPTICAN LM, ZEE DS (1984) A hypothetical explanation of congenital nystagmus. Biological Cybernetics, 50, 119-134. PAGE NGR, BARRATT HJ, GRESTY MA (1984) Gaze abnormalities with chronic cerebral lesions in man. In: Theoretical and Applied Aspects of Eye Movement Research. Edited by A. G. Gale and F. Johnson. Amsterdam: North-Holland, pp. 397-402. SHALLO-HOFFMANN J, WATERMEIER D, PETERSEN J, MUHLENDYCK H (1988) Fast-phase instabilities in
normally sighted relatives of congenital nystagmus patients—autosomal dominant and x-chromosome recessive modes of inheritance. Neurosurgical Review, 11, 151-158. SHARPE JA (1986) Supranuclear disorders of horizontal eye motion. Seminars in Neurology, 6, 155-166. TYCHSEN L, LISBERGER SG (1986) Maldevelopment of visual motion processing humans who had strabismus with onset in infancy. Journal of Neuroscience, 6, 2495—2508. TYCHSEN L, HURTIG RR, SCOTT WE (1985) Pursuit is impaired but the vestibulo-ocular reflex is normal in infantile strabismus. Archives of Ophthalmology, 103, 536—539. VAN WEERDEN TW, HOUTMAN WA (1984) Manifest latent nystagmus of late onset: a case report.
Ophthalmologica, 188, 153-158. WORTH C (1908) Squint: its Causes, Pathology and Treatment. Philadelphia, Blakiston Sons and Company. {Received February 12, 1992. Revised March 20, 1992. Accepted April 15, 1992) Downloaded from by guest on February 14, 2015
NEUROLOGY OF LATENT NYSTAGMUS by MICHAEL A. GRESTY, 1 TERESA METCALFE, 1 CHRISTINE TIMMS, 2 JOHN ELSTON, 4 JOHN LEE3 and CHRISTOPHER LIU 3 (From the 'MRC Human Movement and Balance Unit, National Hospital for Neurology and Neurosurgery, the department of Ophthalmology, The Hospital for Sick Children, 3Moorfields Eye Hospital, London and 4The Radcliffe Infirmary, Oxford, UK) SUMMARY
INTRODUCTION
The term latent nystagmus is used to refer to a nystagmus which appears or is markedly enhanced when one eye is covered with the uncovered eye free to view. The uncovered eye drifts off target with a slow phase movement in a nasal direction. The drift is corrected with a nystagmus beat in a temporal direction to refix the eyes on target. The eye under cover also moves with the same nystagmus waveform, although sometimes with different amplitude if it is in an extreme orbital position. Correspondence to: Michael A. Gresty, MRC Human Movement and Balance Unit, National Hospital for Neurology and Neurosurgery, Queen Square, London WC1N 3BG, UK. © Oxford University Press 1992
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We report eye movement findings in 30 patients with latent nystagmus and who were found to have a variety of associated oculomotor disorders. Latent nystagmus is defined clinically as nystagmus which appears on covering one eye and beats towards the uncovered eye. Recordings showed that the latent nystagmus in 28 patients had slow phases with linear or exponentially decreasing velocity. This nystagmus is termed 'LN'. In 13 of these patients certain manoeuvres (e.g. pursuit) provoked nystagmus with exponentially increasing slow phase velocities characteristic of the congenital form of nystagmus termed 'CN' and we propose that this is a forme fruste of CN. In two patients the nystagmus provoked by cover was latent CN. Twenty-nine patients had a history of strabismus and one had a marked phoria. Some patients had amblyopia whilst others had normal vision in each eye. Although binocular vision was usually absent, six patients had varying degrees of stereopsis. A temporonasal predominance of monocularly elicited optokinetic response previously associated with LN, was present only in a minority of patients. Some responses were bidirectionally absent or of low velocity, possibly the result of a cortical impairment of visual motion detection. The most deranged responses had slow phases which were in the opposite direction to the stimulus as described in CN. The presence of 'forme fruste' CN in many of these patients suggests that some of the derangements of optokinetic responses are due to CN. The findings indicate a greater overlap between the incidences of LN and CN than previously estimated. Thirty percent of patients had large saccadic 'square wave' intrusions. These were not present when there was marked amblyopia. They are attributed to a competitive incongruence of visual fields and eye positions. Dissociations found between the presence and severity of strabismus, stereopsis, amblyopia and optokinetic abnormalities point to these features being relatively independent although associated in typical clusterings. This is evidence against the theory that strabismus and LN are directly caused by nasotemporal optokinetic imbalance which persists because of failure to develop binocular vision. The variability of findings favours the view that LN and CN arise from a genetic or acquired embryological disorder with various degrees and directions of expression.
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M. A. GRESTY AND OTHERS
Latent nystagmus is most commonly associated with infantile or childhood onset esotropia and amblyopia. In addition, subjects with latent nystagmus are reported to have a poor monocular optokinetic response to target motion in a nasotemporal direction (Tychsen and Lisberger, 1986; Kommerell, 1988). Nasotemporal asymmetry of optokinetic nystagmus (OKN) is physiological in the neonate (Atkinson and Braddick, 1981; Naegele and Held, 1982) and it has been suggested that its persistence is the fundamental abnormality in infantile esotropia. Some subjects with LN also have 'dissociated vertical deviation' (DVD) which is an elevation and extortion of the eye under cover.
METHODS Patient selection Thirty patients were admitted to the study because examination in the clinic had revealed a nystagmus which was provoked by cover testing and which beat towards the uncovered eye. Patients who had a clearly visible, persistent, spontaneous or gaze-evoked nystagmus with both eyes viewing were excluded from the study on the basis that such nystagmus was likely to be CN. The selection included patients with very small amplitude 'manifest LN' which was markedly enhanced on cover testing and was sometimes detected on clinical examination. All patients found to have relevant neurological disease were excluded from the study. These criteria were aimed at biasing selection against including patients with obvious features likely to be CN. Eye movement recordings Eye movements in the horizontal plane were recorded from separate eyes with DC coupled electrooculography. Occasionally infrared corneal reflection oculography (bandwidth DC > 100 Hz) was used
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Latent nystagmus waveforms: LN or CN? A nystagmus that is latent may have two different types of waveform. Although they are both generically 'congenital' the two waveforms imply different kinds of mechanism (Dell'Osso et al., 1979; Dell'Osso, 1985). Accordingly, one must adopt precise criteria to distinguish between these two varieties which necessarily depend on eye movement recordings (Dell'Osso and Daroff, 1975; Dell'Osso et al., 1979). One latent type of nystagmus has a slow phase with exponentially decreasing or linear velocity in all positions of gaze; this is termed 'LN'. A second type has slow phases with exponentially increasing velocity involving a complex variety of waveforms and is termed 'CN'. (The CN type may be more familiar to the reader as the conjugate spontaneous or gaze-evoked nystagmus, often of florid appearance and present with binocular viewing.) Both LN and CN can coexist in a patient with either being the more dominant waveform or mixed in equal proportions; LN and CN with a marked latent component are illustrated in Fig. 1. The present study examined the relationships between ophthalmological and oculomotor findings in a sample of patients with latent nystagmus with emphasis on optokinetic responses because of their relevance to theories of latent nystagmus and strabismus. The findings also have implications for clinical diagnosis since latent nystagmus can be associated with a number of oculomotor abnormalities resembling disorders in acquired neurological disease. Accordingly, recognition of the characteristics of latent nystagmus may obviate extensive investigations.
NEUROLOGY OF LATENT NYSTAGMUS
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on children who would not tolerate electrodes. Recordings were made of eye movements in primary gaze and 30° right and left gaze with both eyes viewing and with each eye separately occluded. All but the six youngest subjects (aged 5—7 yrs) underwent vestibular testing of the horizontal vestibular ocular reflex on the motorized chair using rotational velocity steps or sinusoidal oscillation in darkness. Vestibular function will not be discussed because it is known to be normal in LN (Tychsen et al., 1985). However, vestibular responses were useful for classifying patients because they sometimes have waveforms suggestive of CN.
RESULTS
General patient characteristics Essential clinical features of the patients surveyed are given in Table 1. Twenty-eight patients had a history of strabismus beginning in childhood. When examined, 15 were convergent, eight were divergent and one alternated. Four of the patients with childhood strabismus had straight eyes following surgery or patching. Two patients had no history of strabismus but were noted to have phorias (in phoria the eyes are normally orthotropic but immediately drift into misalignment when covered). Four patients had gross binocular vision (BV) at 400' to 800' arc and one had good stereopsis at 70' of arc (measured by synoptophore or on Stereo Optical Company Inc., Stereo Test). This latter patient also had CN-type nystagmus in the far right lateral gaze which had been undetected in the initial clinical selection. Unfortunately, BV was not assessed in the two patients without strabismus. However, rapid return to orthotropia on removing cover indicates that they had some useful BV. Thirteen patients had a amblyopic eye in which visual acuity was equal to or less than 6/18. However, 10 had acuities in both eyes equal to or better than 6/9. Dissociated vertical divergence was present in 12 patients of whom nine had been operated on to correct the strabismus. In all, 13 patients had received surgery on the extra-ocular muscles. Two had botuljnum toxin injections. Patients 4 and 5 were sisters and patients 28 and 29 were mother and daughter. A further five patients had a family history of strabismus. Symptoms. Although not commonly appreciated, latent nystagmus may be symptomatic.
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Optokinetic and pursuit stimuli Pursuit and optokinetic responses were tested on all subjects with both eyes viewing and with each eye separately occluded. Pursuit stimuli comprised a red laser dot target moving over a plain blue background with a sinusoidal trajectory at frequencies variable from 0.1 Hz to 0.8 Hz with a peak amplitude of 20°. Optokinetic testing was aimed at determining how responses were related to stimulus velocity and also to position of the eyes in the field of gaze after the methods of Halmagyi et al. (1980) and Kommerell and Mehdorn (1982). Optokinetic stimuli were delivered with a 2 m diameter, whole field rotating drum with an illuminated inner surface of black and white vertical stripes, each subtending 10°. The subject was seated in the centre of the drum with head restrained. The procedure consisted of accelerating the drum at 10 deg/s2 from rest up to 80 deg/s. The acceleration was interrupted at 20, 40, 60 and 80 deg/s so that the drum rotated at constant velocity at these speeds. During constant velocity stimuli the subject was instructed to look at the portion of the drum which was straight in front and also to look at the drum with his eyes deviated over to the right and to the left by about 25—30°. After the 80 deg/s stimulus the drum decelerated to rest. To plot the graphs shown in Fig. 5, slow phase eye movement velocity was measured by aligning a protractor radius with the linear slow phases and measuring the inclination. Averages of the velocities of each slow phase occurring during a 4 s interval taken when the eyes were in the required field of gaze were calculated.
R6/6 L6/6 R6/36 L6/5
R6/5 L6/5
R6/I8 L6/4
R6/12 L6/18 BEO 6/6 R6/9 L6/9 pi BEO 6/9
6 M 33
8 M 44
9 M 13
10 F 2 I
RCS accommodative
R. exophoria
LCS
16 M 38
R6/6 L6/6
RDS
ADS
RCS DVD RDS
RCS
R6/I2 L6/6 R6/6 L6/6
14 M 5
15 M 38
LCS DVD
LCS
R6/9 L6/I8
LDS DVD
13 M 10
ACS
LCS DVD
LDS (minimal)
RDS
R6/12 p) L6/9 BEO 6/5
LCS DVD
?
RCS
?No strabismus—marked esophoria
RCS
Childhood 'squint'
LCS
LCS L/R DVD
12 M 16
II F 15
7 M7
R6/6 L6/24 + BEO6/5
5 F II
ACS
RDS DVD
7
R6/I8 L6/24 BEO6/5
RCS
LCS
R6/I2 L6/I8 R6/I8 L6/9
Present diagnosis RCS DVD
RCS
Original diagnosis
R6/9 L6/9
Acuities diagnosis
4 F 13
3 M 27
2 M 6
Patient no. Isex and age (yrs) 1 F9
TABLE 1. PATIENT
Surgery
Surgery X 1 Glasses
Surgery X4
Glasses
Surgery XI Patching, glasses
Surgery x I Glasses
Patching
R patch Surgery X2 Glasses
R patch
Glasses
Surgery X2
Treatment
Other history
Hyperactive, learning problems
'Qumsy child'
L ptosis
Speech therapy OpBoclonus?
Anxiety complex
Mild cerebellar syndrome? Patients 4 and 5 are sisters
Paroxysmal head shaking somatic tics, epilepsy
CLASSIFICATION Downloaded from by guest on February 14, 2015
CN
?
+
CN?
400'
BV?
O H X PI 73
Z D
m
73
2 > a
R679 L6/24
R6/I2 L679
R3/60 L6/24 BEO 6/9
R6/6 L676
R6/6 L6/6
R6/9 L6/18
R6/6 L6/5 R6/6 L6/6
21 M 25
22 F 6
23 M 67
24 M 19
25 F 20
26 F 35
27 F 2 4
R6/9 L6V12
30 M 42
LCS DVD
ACS nystagmus head nodding CS
LCS
Straight
CS L/ACS
Looks straight DVD
Surgery X2
Surgery X 2
R patch
Enhanced spontaneously
Patients 28 and 29 are mother and daughter*""
(Enhanced by accident)
(Enhanced by accident)
CN
+++
400'
—
-
7
-
70'
-
400'
-
ADS
Albinism'"
••*•»
*•
4007800' Botox
Surgery Glasses
Surgery
Surgery Glasses
Surgery Glasses
RDS
No history of strabismus, eyes straight with mild phoria CS Looks straight
?Exotropa
LCS
? RC-DS
LCS DVD
ACS
RCS DVD
LCS DVD
ACS
•Sister with strabismus without LN, "daughter with strabismus without LN, •"brother with strabismus and albinism without LN, ••••second daughter with strabismus without LN, " " • m o t h e r and sister with strabismus without LN Binocular vision assessed on Titmus fly test and synoptophore. 'Botox' signifies that patients had received botulmum toxin for correction of strabismus. The presence of CN in patients' eye recordings was quantified in rank order by awarding a + for each manoeuvre which provoked a CN waveform. The manoeuvres included were: cover testing of right and left eye, gaze holding to the right and left, pursuit under monocular and binocular conditions, optokinetic responses in primary and to right and left gaze nnd monocular and binocular responses considered as separate conditions and vestibular evoked nystagmus. Possible CN waveforms were ascribed a ?. Binocular vision is rated in minutes or arc or - indicates no BV. RCS «• right convergent strabismus; LCS £> ^ v
H
m
-)
r
""
O
f" O •
nasotemporal asymmetry of OKN, commonly said to be typical in LN, was seen in only four patients of whom one (patient 22) had partially expressed oculocutaneous albinism. The directional asymmetries which can be more than 20 deg/s are not a simple summation of LN with the OKN and an additional explanation must be sought. Figure 5B shows the responses of subject whose raw data records are given in Fig. 4. With monocular viewing there is a velocity saturation of nystagmus slow phase at about 20—30 deg/s rightwards and leftwards and the direction of the slow phase is inverted with respect to the stimulus direction if the eyes are deviated in the direction of drum rotation. Binocularly there is still velocity saturation which are below normal, to the right at 30 deg/s and to the left at 20 deg/s with reversal of nystagmus direction when the eyes are deviated to the left. Figure 5c shows responses whose velocities with binocular and right eye viewing
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Reversion
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NEUROLOGY OF LATENT NYSTAGMUS
OKSR
Reversal
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LE (covered)
1 s
FIG. 4. A, optokinetic responses to rightwards (OKS R) and leftwards (OKS L) stimuli which invert in direction as a function of position of the eyes. With right eye (RE) covered the nystagmus generated when the eyes are in the left field of gaze is in the opposite direction to stimulus motion. With left eye (LE) covered the nystagmus when the eyes are in the right field of gaze is in the opposite direction to stimulus motion. Although the most part of nystagmus has linear or exponentially decreasing waveforms that seen during reversal of direction on lateral gaze is suggestive of CN. B, magnified example of the nystagmus with slow phase in the opposite direction to the stimulus motion in response in high velocity optokinetic stimuli. With the eyes in the right field of gaze the nystagmus has a CN-type waveform. The tracings are for patient 6.
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M. A. GRESTY AND OTHERS C
Response velocity
80 60 40 20
Stimulus velocity
0 -20
-80 - 8 0 - 6 0 - 4 0 -20 0
B
20 40 60 80
Response velocity
80
20 40 60 80
Response velocity Binocular viewing
40
40
20
20..--
Stimulus velocity
0
0>
-40
^40
-60
-60
0
20 40 60 80
80
-80 -80 -60 -40 -20 0 80 60
60
20 40 60 80 Right eye viewing
40
40
20
20
Stimulus velocity
0
0'
-20
-20
-40
^40
-60
-60
0
20 40 60 80
80
-80 _80 -60 -40 -20 0 80
60
60
40
40
20
20
0 tr -20 -40
0
-60
-80 -80 -60 -10 -20 0
20 40 60 80
-20 -40 -60 -80 _80 -60 -10 -20 0
20 40 60 80 Left eye viewing
Stimulus velocity
20 40 60 80
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-20
-20 - _ . .
-80 -80-60-40-20
D 80 60
60
-80 -80-60-^40-20
-60 -80 -80 -60 -40 -20 0
NEUROLOGY OF LATENT NYSTAGMUS
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exceeded stimulus velocity for leftwards stimuli up to a saturation at 60 deg/s. Responses for nasal wards stimuli were absent on monocular viewing. Figure 5D shows responses to optokinetic stimuli which consist of a persistent right beating nystagmus with low slow phase velocities under almost all testing conditions. This subject had a marked right beating LN with no evidence of CN so one might have thought that any leftwards optokinetic response would be enhanced with the nystagmus. This was not the case which raised doubt as to whether there is any response in this direction. The uniformity of the nystagmus during optokinetic stimuli suggests that it might be an instability, triggered off in some way by the stimulus. Vertical optokinetic in latent nystagmus On clinical examination using a hand-held target or drum, most patients had apparently normal or near normal vertical optokinetic and pursuit responses both with monocular and binocular viewing, despite marked horizontal abnormalities. This finding demonstrates the independence of the horizontal and vertical systems. Several patients had sluggish responses, particularly during monocular stimulation, but in the absence of quantification their significance is uncertain. These sluggish responses were not systematically associated with DVD as one might expect. Of note, vertical optokinetic responses could appear normal with monocular stimuli presented to a severely amblyopic (6/18 — 36) eye.
Presence of 'forme fruste' of CN-type nystagmus Fifteen patients whose LN had linear or exponentially decreasing waveforms were found to have CN-type nystagmus waveforms during certain manoeuvres, in particular during pursuit and optokinetic stimulation. For example, in Fig. 4, when the eyes are in the right field of gaze, the nystagmus slow phase is in the opposite direction to the motion of the optokinetic drum and has a complex waveform similar to CN. This waveform is not the result of an interaction between gaze-evoked nystagmus and an optokinetic response since it does not occur in all circumstances when the two are opposed in direction but is specific to certain eye positions. In the context of clinical diagnosis a spontaneous nystagmus with this waveform would normally be taken as evidence for CN (Gresty et ai, 1984; Kelly et ai, 1989) and therefore we propose that this is a 'forme fruste' of CN. The extent to which CN waveforms were evident in a subjects
FIG. 5A,B,C,D. Plots of slow phase eye velocity as a function of stimulus velocity for various subjects with the eyes in centre, right and left gaze and with binocular or monocular viewing. The vertical lines on plot A are the ± I SD limits of normal performance according to our laboratory standards. Rightwards direction is positive, A and c: , binocular; ,righteye; , left eye. B and D: , look centre; , look right; , look left. Tracings are for patient 28 (A), patient 6 (B), patient 9 (c) and patient 23 (D).
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Pursuit responses Pursuit response abnormalities were similar to OKN abnormalities and there was no evidence of dissociation between optokinetic and pursuit performance in the form of robust pursuit and deranged OKN. In some patients optokinetic responses were better formed than pursuit, probably because the larger target is a stronger stimulus. Of note, pursuit was particularly provocative of saccadic square wave intrusions (Fig. 6).
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M. A. GRESTY AND OTHERS i—i—i—i—i—i—i—i
i
i
r
Saccadic instabilities.
i
i i i—rn—i—i
LE (covered) FIG. 6. Pursuit responses to a sinusoidal target (patient 9). Square-wave saccadic intrusions can be during either leftwards or rightwards pursuit with monocular or binocular viewing, consistently taking the eyes towards the left. Note slow phases opposite to target motion with left eye (LE) following leftwards and the right eye (RE) following rightwards.
eye movements is shown in the tables for direct comparison with the incidence of other features. Ten patients had CN which was provoked consistently by certain manoeuvres and a further five had occasional brief episodes of CN. Saccade abnormalities: saccadic square-wave intrusions Eleven patients had involuntary saccades or series of saccades which took the eyes away from the location of the target which the subject was required to fixate or pursue and then returned the eyes back on target giving an overall shape of 'square-wave
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HI
NEUROLOGY OF LATENT NYSTAGMUS
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intrusions' (Fig. 6). If subjects failed to suppress these movements after encouragement and practice to stay 'on target' and episodes occurred frequently, their saccadic control was judged to be abnormal. The amplitudes of the square waves could be as high as 20° and occurred with monocular or binocular viewing. Pursuit was particularly provocative of square-wave intrusions (Fig. 6). Relationships between LN, CN, amblyopia, OKN and square-wave intrusions The strength of associations between the various features accompanying LN is relevant to establishing those which always occur together and may be causally related. Since the 'strength' of appearance of certain features was highly variable and difficult to measure as a magnitude, these features were rank ordered according to the criteria given in Table 2
TABLE 2 DERANGEMENT OF OPTOKINETIC RESPONSES IN LN AND RELATIONSHIP WITH CN, AMBLYOPIA AND SACCADIC INSTABILITY Binocular R L
CN waveform
_+?
Amblyopia ? 6/18+
+-7 +
R+L R+L L
+
+ + + +
Square waves
77 R+L R
+ +
_+? +
+ +
+
17 F 6
±
±
+ +
+ +
+ + + ? + + + + + +
2M6
+
+
12 M 16 3 M 27 8M44 6 M 33 25 F 20 I0F2I
+ + + + + +
+ + + + + +
+ + + + + + + +
+ +
??
+
+
+ +
++++ ? +
+ + +
+
4 F 13* 20 F 10 24 M 19 15M38 5 F 11* 7M7 16 M 38 18 F 6 23 M 67 9M13 30M42
+ +
+ +
+
+ + + + + + + + + + + + +? + + + ? + + + + ++ ++ +
+ +
+ +
+ +
L
R+L ?
++++ +++++
+
R+L R+L
R R+L
+ indicates the presence of definite abnormality. ? indicates abnormality suspected or intermittently present. Optokinetic abnormalities are shown for binocular and monocular viewing with drum motion to the left (L), andright(R). Derangements of response include slow phase of nystagmus in the opposite direction to stimulus motion or lack of modulation of the slow phase velocity of the nystagmus response by changes in the stimulus velocity (this criterion includes, e.g. persistent low velocity nystagmus in response to all stimuli or very high velocity nystagmus provoked by the slightest movement of the drum. Optokinetic abnormalities underlined conform to the primitive pattern of temperonasal > nasotemporal asymmetry. Saccadic square-wave intrusions are shown by their predominant rightwards, leftwards directionality.
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Patient no. I sex and age (yrs) 21 M 25 28 F 4 2 22 F 6 1 F 9* 29 F 11 26 F 35 11 F 15 27 F 24 19F41 13 M 10 14 M 5
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M. A. GRESTY AND OTHERS
DISCUSSION
Theories of the origin of LN Some theories of LN (e.g. Tychsen and Lisberger, 1986; Kommerell, 1988) propose that strabismus and LN are a consequence of the normal physiological temperonasal > nasotemporal preponderance of optokinetic following seen in the neonate before the development of binocular vision (Atkinson and Braddick, 1981; Naegele and Held, 1982). If binocular vision fails to develop, each eye experiences a persistent nasalwards tonus via the asymmetrical optokinetic stimulation which eventually results in convergent strabismus. When one eye is viewing, the tonus is unopposed and becomes manifest as the slow phase of LN. As an additional factor there may be a cortical impairment of temporally directed motion detection (Norcia et al., 1991). This theory accepts a basic (genetic) defect, originally postulated by Worth in 1908 as 'congenital absence of the fusion faculty', but emphasizes ontogenetic factors in the evolution of the various features as a Chevasse's theory of 1939 'structural development on one hand and the rewards of use on the other' {see Lyle, 1950). A different kind of theory which specifically addresses the mechanism of the nystagmus proposes that LN arises due to problems with egocentric direction, visual field direction and the positions of the eyes (Dell'Osso et al., 1979; Abadi, 1980; Dell'Osso and Daroff, 1981). Dell'Osso's explanation is the more specific: normally a target is perceived as 'straight ahead', although there is a net vergence between the two eyes. Upon covering one eye the vergence becomes apparent in that the target is displaced nasalwards with respect to the seeing eye although it is still egocentrically in the same place. In LN these relationships are misinterpreted. When one eye is covered, an inappropriate
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to establish as scale of how much they were in evidence. This scale is shown in Table 2 by the number of plus signs ascribed to a feature. For non-parametric statistical analysis each plus sign was given the value 1. A question mark was assigned the value 0.5. Amblyopia was assigned 0 if acuity was more than 6/18 and 1 if less than 6/18. Square waves were awarded 1 for each right or left direction in which they presented, 0 if absent. On Spearman rank correlation there was a positive and significant correlation between severity of OKN abnormalities and the presence of CN-type waveforms; r = 0.46; P = 0.005 which was attained both with and without the inclusion of the two subjects who had CN on lateral gaze. However, it should be stressed that despite this group association, at least four patients with no evidence of CN in their eye movement recordings had deranged optokinetic responses for all or most viewing conditions. Optokinetic abnormalities were unrelated to the presence of severe amblyopia, Mann-Whitney U test, U = 88.8; P = 0.8 or to the presence of square-wave intrusions, Kruskal Wallace ANOVAR by ranks, H(2) = 0.016; P = 0.99. On the Mann-Whitney U test the presence of CN-type waveforms was unrelated to amblyopia, U = 68.5; P = 0.24 or to the presence of square-wave intrusions; U = 78; P = 0.57. The presence of a marked amblyopia (11 patients) and the occurrence of square-wave intrusions (11 patients) tended to be mutually exclusive, Mann-Whitney U test, U = 49; P = 0.04. Only one patient had both.
NEUROLOGY OF LATENT NYSTAGMUS
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Nature of OKN responses The optokinetic disorders in LN are more complex than hitherto described. In particular, as shown in Table 2, nasotemporal asymmetry which has been associated with LN (Kommerell and Mehdorn, 1982; Tychsen et al., 1985; Hatayama et al., 1986; Tychsen and Lisberger, 1986) is not the norm. In the simplest case the optokinetic response is totally absent or has a normal configuration but only achieves low velocity. In these cases a high velocity spontaneous nystagmus was not present, so there was adequate retinal stimulation and opportunity to observe responsivity over a wide range of velocities. This means that a well-formed but low velocity response suggests a direct impairment of optokinetic performance. It has been proposed that this is the result of an impaired velocity signal in visuo-parietal cortex (Norcia et al., 1991). For example, a poor response to a temporally directed stimulus to the right eye could be ascribed to a lesion affecting the velocity input from temporal retina to the right visuo-parietal cortex. This hypothesis awaits psychophysical testing but is corroborated by preliminary studies on movement evoked visual evoked potentials (Norcia et al, 1991). In some patients the onset of an optokinetic stimulus triggered a nystagmus which thereafter was not modulated by the velocity or direction of the stimulus. Such nystagmus
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nasalwards tonus is exerted on the eyes (with respect to the seeing eye) which causes nystagmus. Evidence against strabismus and LN being caused by optokinetic asymmetry is the number of dissociations and lack of consistent proportional relationships between these features. The optokinetic responses in LN can vary from being normal to apparently absent or 'inverted'. Although all patients with LN have strabismus or unstable phoria (Dell'Osso et al., 1979, 1983Z?) some manage their phorias well (patient 6 who only had LN and strabismus on vergence). Failure of BV is also not a necessary condition for LN since a rare patient with strabismus can have BV (patient 25) and subjects with unstable phoria have useful BV as shown by their rapid recovery of orthotropia when cover is removed. Some of our subjects with LN had familial strabismus with parent and siblings without nystagmus (Table 1). Our findings favour an alternative theory to optokinetic asymmetry as a cause of LN. It is well known that strabismus and CN can be familial and eight of our patients had parent and siblings with strabismus, both with and without nystagmus. This strong element of inheritance together with the dissociations to be found between the various oculomotor abnormalities in LN are in favour of them being variable genetic expressions as proposed by Jung and Komhuber (1964). In addition, some cases may be due to acquired embryological disorders involving mechanisms similar to inherited disorders. If problems with egocentric direction are the specific mechanism of LN, one might expect that possible confusion between eye, target and egocentric direction to be minimal with far targets and enhanced with near targets requiring greater vergence. In support of this notion it is of note that the LN in patients 6 could only be provoked when there was some degree of vergence. Incidentally, there appear to be no studies of the intensity of LN with respect to various target distances and positions of the eyes in the orbit to provide evidence for a more detailed theory of LN. An analogous mechanism is proposed for saccadic instabilities as discussed below.
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Relationship between mechanisms of LN and CN and optokinetic responses Patients with pure LN do not have evidence of derangement of brainstem oculomotor mechanisms. Saccades and the vestibular-ocular reflex (Tychsen et al., 1985) are intact. Many patients have bidirectionally normal pursuit and OKN responses under certain conditions, i.e. with either both eyes or one eye viewing (Tychsen and Lisberger, 1986 and this study). This negative evidence suggests that the disorder underlying LN is at a cortical level. In contrast, it is proposed that CN is caused by positive feedback on the neural velocity-position integrator in the brainstem causing the eyes to drift off target with an increasing velocity (Dell'Osso and Daroff, 1981; Optican and Zee, 1984). Dell'Osso (1985) estimates that 80% of the nystagmus associated with strabismus is CN, pure LN accounts for 15% with mixtures of the two comprising only 5%. Our sample was biased against CN and so probably corresponds to the categories LN and LN+CN (i.e. 20%). Since more than 50% of our patients were found to have CN features (identified in a wider range of manoeuvres than used in other surveys), possibly up to half of the patients with LN also have some CN. The strong association between LN and CN could be taken to indicate that their underlying genetic or acquired embryological disorders are similar but manifesting in different ways according to expression factors. This view would point to a more unified theory of the aetiology of 'congenital nystagmuses'. Precisely how the mechanisms of LN and CN interact when both are present is difficult
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may be a system instability provoked by the moving visual field as suggested by Dickinson and Abadi (1990). The underlying optokinetic response may be weakly intact but is masked or even adapted out (Dickinson and Abadi, 1990). Amongst the more striking abnormalities were nystagmic responses whose slow phase directions were dependent upon the position of the eyes in the field of gaze (e.g. Fig. 4). This type of 'reversed' or 'wrong way' response was observed by Tychsen and Lisberger (1986) during pursuit tasks. These authors associated the phenomenon with low velocity target motion which was not always the case with our patients. In extreme cases the slow phases were of higher velocity than the stimuli (either in the same or opposite directions). Occasionally responses could oscillate in direction, apparently as a function of stimulus velocity (Figs 3,4). Such abnormalities are similar to those in fully developed CN (Halmagyi et ai, 1980). In CN, pursuit (Dell'Osso, 1986; Kurzan and Buttner, 1989) and optokinetic signals (Kurzan and Buttner, 1989) may be intact but are masked by, or adapted in, the presence of the nystagmus. The result is that they may have velocities which are abnormally high or 'inverted' depending upon how the stimulus affects the null point of the nystagmus. Although the more deranged optokinetic responses tended to occur when there was also congenital type nystagmus (Table 2), occasional patients with no evidence of CN-type waveforms in their recordings had marked derangements (e.g. Figs 2, 3; patient 13). One must conclude that responses with slow phase velocities greater than the stimulus or apparently inverted in direction are likely to be related to CN mechanisms even when an explicit CN waveform is not evident. In summary, there are two likely mechanisms for abnormal optokinetic responses in subjects with LN: (i) degradation of visual motion signals in the cortex; (ii) masking of the optokinetic response with the mechanisms of both LN and CN.
NEUROLOGY OF LATENT NYSTAGMUS
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to ascertain. In some cases the CN only appears when there is a strong velocity signal, such as pursuit, which displaces the null sufficiently to reveal the CN. When CN appears on cover testing the nasalwards drift caused by the LN mechanism might trigger the CN instability. Difficulties of interpretation arise because CN itself can have apparently linear, velocity increasing or decreasing slow phases which make proportional classification into LN versus CN hazardous (Dell'Osso, 1985).
Implications for clinical neurology Patients with latent nystagmus may show oculomotor disorders with a similar appearance to those seen in acquired neurological disease. However, if the cardinal components of LN, CN and strabismus or unstable phoria are identified, then one can recognize the various other disorders as attendant features which do not imply the presence of an acquired disorder. Accordingly, it is always of value to examine for LN in any patient who is suspected of having an eye movement disorder. Unfortunately, the interpretation of eye movements in the rare patient who may have LN and an acquired oculomotor disorder may be difficult. The amplitude of LN and CN may change throughout life (van Weerden and Houtman, 1984; Gresty et al., 1991, three patients studied here), enhancing spontaneously or with trivial disease and minor head injury. Under these circumstances it can become symptomatic and is particularly suggestive of an acquired disease. Identifying the nystagmus as LN or CN may help to obviate extensive investigations. ACKNOWLEDGEMENTS The authors wish to thank the two referees who reviewed this paper for their valuable, constructive criticism during the editorial process.
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Saccadic square-wave intrusions Subjects with strabismus are known to switch between eyes when viewing to the right and left (Dell'Osso et al., 1983a). This results in a saccade which brings the eye selected for viewing into alignment which can be construed as a convenient manoeuvre. We have shown that saccadic instabilities also occur monocularly with the patient trying to remain on target so that nothing is to be gained by switching eyes. There are two alternative explanations. First, because saccadic intrusions did not occur with severe amblyopia, it would appear that two functioning visual fields are necessary to cause the instability. The saccades could be due to the uncertainty about whether to control eye movements with respect to the visual map of the right eye or the left eye. If the maps have an abnormal correspondence with each other and with the positions of the eyes, a shift of control between maps may result in an eye movement. This mechanism is analogous to that hypothesized by Dell'Osso for LN. (ii) Alternatively, although square waves occur in normal subjects and in a variety of diseases (Jones et al., 1983; Abel etal., 1984; Shallo-Hoffmann etal., 1988), those in our patients are most like descriptions of the 'visual grasp reflex' (Sharpe, 1986) and square waves in patients with cortical lesions (Page et al., 1984). Since saccadic instability is a sign of frontal lobe dysfunction (Guitton et al., 1985), the question is raised of whether there is other evidence for frontal lobe abnormalities in these patients.
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ABADI RV (1980) Pattern contrast thresholds in latent nystagmus. Ada Ophthalmologica, 58, 210-220. ABEL LA, TRACCIS S, DELL'OSSO LF, DAROFF RB, TROOST BT (1984) Square wave oscillation: the
relationship of saccadic intrusions and oscillations. Neuro-ophthalmology, 4, 21—25. ATKINSON J, BRADDICK O (1981) Development of optokinetic nystagmus in infants: an indicator of cortical binocularity? In: Eye Movements: Cognition and Visual Perception. Edited by D. F. Fisher, R. A. Monty and J. W. Senders. Hillsdale, NJ: Lawrence Erlbaum, pp. 5 3 - 6 4 . CHEVASSE FB (1939) Worths Squint. Philadelphia: Blakiston Sons and Company. DELL'OSSO LF (1985) Congenital, latent and manifest latent nystagmus—similarities, differences and relation to strabismus. Japanese Journal of Ophthalmology, 29, 351 —368. DELL'OSSO LF (1986) Evaluation of smooth pursuit in the presence of congenital nystagmus. Neuro-
ophthalmology, 6, 383-406. DELL'OSSO LF, DAROFF RB (1975) Congenital nystagmus waveforms and foveation strategy. Documenta
Ophthalmologica, 39, 155-182. DELL'OSSO LF, DAROFF RB (1981) Clinical disorders of ocular movement. In: Models of Oculomotor Behavior and Control. Edited by B. L. Zuber. Boca Raton, FL: CRC Press, pp. 233-256. DELL'OSSO LF, SCHMIDT D, DAROFF RB (1979) Latent, manifest latent, and congenital nystagmus. Archives
of Ophthalmology, 97, 1877-1885. DELL'OSSO LF, ELLENBERGER C, ABEL LA, FLYNN JT (1983a) The nystagmus blockage syndrome.
Congenital nystagmus, manifest latent nystagmus, or both? Investigative Ophthalmology and Visual
Science, 1A, 1580-1587.
GRESTY MA, BRONSTEIN AM, PAGE NG, RUDGE P (1991) Congenital-type nystagmus emerging in later
life. Neurology, Cleveland, 41, 653-656. GUITTON D, BUCHTEL HA, DOUGLAS RM (1985) Frontal lobe lesions in man cause difficulties in suppressing reflexive glances and in generating goal-directed saccades. Experimental Brain Research, 58, 455 —472. HALMAGYI GM, GRESTY MA, LEECH J (1980) Reversed optokinetic nystagmus (OKN): mechanism and clinical significance. Annals of Neurology, 7, 429—435. HATAYAMA R, SASANO Y, KAWSAI K, MATSUZAKI H (1986) A study of latent nystagmus by the electro-
oculogram—fixation, pursuit eye movement, optokinetic nystagmus. Journal of Ophthalmology of Japan, 90, 542-549. JONES A, FRIEDLAND RP, KOSS B, STARK L, THOMPKINS-OBER BA (1983) Saccadic intrusions in Alzheimer-
type dementia. Journal of Neurology, 229, 189-194. JUNG R, KORNHUBER HH (1964) Results of electronystagmography in man: the value of optokinetic, vestibular, and spontaneous nystagmus for neurologic diagnosis and research. In: The Oculomotor System. Edited by M. B. Bender. New York: Harper and Row, pp. 428-482. KELLY BJ, ROSENBERG ML, ZEE DS, OPTICAN LM (1989) Unilateral pursuit-induced congenital nystagmus.
Neurology, Cleveland, 39, 414-416. KOMMERELL G (1988) Ocular motor phenomena in infantile strabismus. In: Physiological Aspects of Clinical Neuro-Ophthalmology. Edited by C. Kennard and F. Clifford Rose. London: Chapman and Hall, pp. 357-375. KOMMERELL G, MEHDORN E (1982) Is an optokinetic defect the cause of congenital and latent nystagmus? In: Functional Basis of Ocular Motility Disorders. Edited by G. Lennerstrand, D. S. Zee and E. L. Keller. Oxford: Pergamon Press, pp. 159-167. KURZAN R, BuTTNER U (1989) Smooth pursuit mechanisms in congenital nystagmus. Neuro-ophthalmology, 9, 313-325. LYLE TK (1950) Accommodational and other squints primarily related to the state of the refraction. In: Worth and Chavasse 's Squint: The Binocular Reflexes and the Treatment of Strabismus. Eighth edition. Edited by T. K. Lyle. London: Balliere, Tindall and Cox, pp. 125-146.
Downloaded from by guest on February 14, 2015
DELL'OSSO LF, TRACCIS S, ABEL LA (19836) Strabismus—a necessary condition for latent and manifest latent nystagmus. Neuro-ophthalmology, 3, 247—257. DiCKJNSON CM, ABADI R (1990) Pursuit and optokinetic responses in latent/manifest latent nystagmus. Investigative Ophthalmology and Visual Science, 31, 1599—1614. GRESTY M, PAGE N, BARRATT H (1984) The differential diagnosis of congenital nystagmus. Journal of Neurology, Neurosurgery, and Psychiatry, 47, 936—942.
NEUROLOGY OF LATENT NYSTAGMUS
1321
NAEGELE JR, HELD R (1982) The postnatal development of monocular optokinetic nystagmus in infants.
Vision Research, 22, 341-346. NORCIA AM, GARCIA H, HUMPHREY R, HOLMUS A, HAMER RD, OREL-BIXLER D (1991) Anomalous motion
VEPs in infants and in infantile esotropia. Investigative Ophthalmology and Visual Science, 32, 436-439. OPTICAN LM, ZEE DS (1984) A hypothetical explanation of congenital nystagmus. Biological Cybernetics, 50, 119-134. PAGE NGR, BARRATT HJ, GRESTY MA (1984) Gaze abnormalities with chronic cerebral lesions in man. In: Theoretical and Applied Aspects of Eye Movement Research. Edited by A. G. Gale and F. Johnson. Amsterdam: North-Holland, pp. 397-402. SHALLO-HOFFMANN J, WATERMEIER D, PETERSEN J, MUHLENDYCK H (1988) Fast-phase instabilities in
normally sighted relatives of congenital nystagmus patients—autosomal dominant and x-chromosome recessive modes of inheritance. Neurosurgical Review, 11, 151-158. SHARPE JA (1986) Supranuclear disorders of horizontal eye motion. Seminars in Neurology, 6, 155-166. TYCHSEN L, LISBERGER SG (1986) Maldevelopment of visual motion processing humans who had strabismus with onset in infancy. Journal of Neuroscience, 6, 2495—2508. TYCHSEN L, HURTIG RR, SCOTT WE (1985) Pursuit is impaired but the vestibulo-ocular reflex is normal in infantile strabismus. Archives of Ophthalmology, 103, 536—539. VAN WEERDEN TW, HOUTMAN WA (1984) Manifest latent nystagmus of late onset: a case report.
Ophthalmologica, 188, 153-158. WORTH C (1908) Squint: its Causes, Pathology and Treatment. Philadelphia, Blakiston Sons and Company. {Received February 12, 1992. Revised March 20, 1992. Accepted April 15, 1992) Downloaded from by guest on February 14, 2015
