Smooth pursuit eye movements in schizophrenics--what constitutes quantitative assessment?

Although a voluminous literature exists on the eye movements of schizophrenic and affective disorder patients, many of the assessments made of smooth pursuit have been qualitative in nature. Most of them have not differentiated between abnormal functioning of the smooth pursuit system and intrusion of inappropriate saccades during a smooth tracking task. Specific identification of the pursuit or saccadic defect is necessary if the origins of the abnormalities are to be understood and related to psychopathology. Analytical techniques, such as the ln(S/N) ratio, although numerical in nature, are still unable to discriminate among pursuit and saccadic defects, as shown by our analysis of simulated tracking. Thus, to understand the effects of psychiatric disorders on the ocular motor system, specific defects must be identified and quantified.

Concordance of smooth pursuit and saccadic measures in normal monozygotic twin pairs.

Although the range of normal ocular motor performance is broad, little is known about the sources of variability. Genetic transmission of eye movement deficits has been described but such possible control of normal function has been little investigated. Characteristics of smooth pursuit and saccades can be examined for the degree of concordance in related individuals. In this pilot study, we studied saccades and pursuit in eight monozygotic (MZ) twin pairs. The statistical analysis of the data used the intraclass correlation of MZ twins (rMZ) to estimate what fraction the covariance of the twin pairs was of the population variance. All saccadic measures showed significant MZ correlations (p < 0.05). Smooth pursuit gains were even more highly correlated (p < 0.001). These results indicate considerable similarity within pairs of twins, particularly for horizontal smooth pursuit, and suggest that larger studies on monozygotic and dizygotic twins would be desirable, to help separate out the relative contributions of environmental and genetic factors.

Saccadic intrusions into smooth pursuit in patients with schizophrenia or affective disorder and normal controls.

Two types of saccadic intrusions into smooth pursuit eye tracking, anticipatory saccades (AS), and square wave jerks (SWJ), were measured in 23 patients with schizophrenia, 16 patients with affective disorder, and 21 normal controls. Constant velocity (5 degrees and 20 degrees/sec) predictable targets were employed. High resolution infrared oculography was employed to record eye movements. Although most subjects had at least one SWJ, there were no significant group differences, and the highest individual rates of SWJ were seen in the normal control group. On the other hand, AS were never seen in normals, but were present in 25%-44% of patients with either schizophrenia or affective disorder. Both patient groups had significantly more AS than controls, but the two patient groups were not significantly different.

Quantitative assessment of smooth pursuit gain and catch-up saccades in schizophrenia and affective disorders.

The smooth pursuit responses to 5 degrees and 20 degrees/sec constant-velocity stimuli were recorded from 23 patients with schizophrenia, 16 affective disorder patients, and 21 normals using low-noise infrared oculography. Pursuit gain, catch-up saccade (CUS) rate and amplitude, and their interrelationships were examined. Gain in the schizophrenic patients was reduced only at 20 degrees/sec, but for both patient groups, CUS rate at 5 degrees/sec was significantly lower than in normals. Using CUS rate at 20 degrees/sec, the patient groups could be distinguished from each other (the rate for schizophrenic patients being highest, and the rate for affectives the lowest) but neither differed significantly from normals. The diagnostic groups did not differ significantly in mean CUS amplitude, although there was a trend for patients to have larger saccades. Gain-CUS rate correlation was strong in normals but reduced or absent in both patient groups. These results indicate that the ocular motor systems of patients with schizophrenia and affective disorders process eye position error abnormally.

Upbeat nystagmus and internuclear ophthalmoplegia with brainstem glioma.

We describe the unusual association of two ocular motor abnormalities: upbeat nystagmus and internuclear ophthalmoplegia in a young woman originally believed to have demyelinating disease. Quantitative eye movement recordings documented a unidirectional defect in upward visual pursuit with preservation of the vertical vestibulo-ocular reflexes. The ocular oscillation was characterized as a type of "pursuit defect" nystagmus. An enhancing lesion of the upper brainstem seen on computerized tomography was primarily localized to the midbrain on pneumoencephalography. Biosy of the lesion disclosed a malignant glial tumor. The patient's course initally progressed but became stable following radiotherapy and chemotherapy during the next eight months. We believe the association of upbeat nystagmus and internuclear ophthalmoglegia should prompt a detailed search for a structural lesion.

Saccadic latency measurements in dementia.

We measured saccadic latencies in patients with Alzheimer's dementia (AD) and other types of dementia. The saccadic latencies for both groups were considerably longer than those for age-matched controls. The prolongation was as extensive in patients with other types of dementia as it was in those with AD. There was no correlation between latency and the severity of the dementia.

Intermittent downbeat nystagmus and oscillopsia reversed by suboccipital craniectomy.

We describe an unusual case of vertical oscillopsia and primary position downbeat nystagmus associated with an adult Arnold-Chiari malformation. A unique aspect of the ocular motor abnormality was the intermittent nature of the nystagmus, which displayed no relationship to head position, emotion, or the Valsalva maneuver. Conventional computed tomography with posterior fossa views was normal, but metrizamide cisternography demonstrated an extramedullary mass originally believed to be a meningioma. There was a dramatic diminution of the visual complaints and downbeat nystagmus after suboccipital craniectomy for an Arnold-Chiari malformation. Nystagmus characteristics were documented by serial quantitative eye movement recordings.

Hyperactive vestibulo-ocular reflex in cerebellar degeneration: pathogenesis and treatment.

We studied a patient with a cerebellar degeneration and hyperactive vestibulo-ocular reflex (VOR). He complained of oscillopsia and blurred vision with head movement. A twofold increase in VOR gain (peak eye velocity/peak head velocity) at high frequencies was associated with a VOR time constant of 6 seconds (low normal). Visual cancellation ("suppression") of the VOR and smooth pursuit were also abnormal. We hypothesized that his high VOR gain was due to dysfunction of olivocerebellar projections. Physostigmine reduced his VOR gain, consistent with the hypothesis that these projections are cholinergic.

Edrophonium test in Eaton-Lambert syndrome: quantitative oculography.

Accurate ocular motility recordings were made of the saccadic responses of five patients with Eaton-Lambert syndrome (ELS). It was found that, contrary to common belief, the ocular motor system is affected. The saccades of ELS patients mimicked those of patients with myasthenia gravis (MG). Both groups exhibited hypometria and multiple, closely spaced saccades. Two patients demonstrated both saccadic facilitation and positive edrophonium tests. The ELS patients had slow or normal saccadic velocities, not the "super-fast" velocities found in patients with ocular MG.

Slow saccades and hypometria in anticonvulsant toxicity.

We report a patient with abnormal saccades in association with anticonvulsant toxicity (phenytoin 27.5 micrograms/ml, phenobarbital 18.8 micrograms/ml). The patient looked toward visual targets either with multiple, small, hypometric saccades or with single slow saccades. These abnormalities resolved when anticonvulsant levels returned to therapeutic range. Thus, slow saccades may be clinical evidence of anticonvulsant toxicity.

Hereditary congenital nystagmus and gaze-holding failure: the role of the neural integrator.

Congenital nystagmus (CN) may be due to an instability of the neural integrator responsible for gaze holding. This longitudinal study tests that hypothesis, investigates the saccadic instabilities of relatives, and assesses the effects of afferent stimulation on both the CN and the coexisting gaze-holding failure. We recorded four siblings who had CN and gaze-holding failure while fixating in primary position and lateral gaze. In lateral gaze, the CN waveforms were superimposed on the centripetal drift caused by the gaze-holding failure; the drift time constants ranged from 300 to 1,450 msec. CN waveforms lacked extended foveation periods. Saccadic instabilities were present in the father and two clinically unaffected siblings; the mother's eye movements were normal. We conclude that CN in the subjects of this study, and in others with idiopathic CN, is not due to gaze-holding abnormalities, and we speculate that development of the fixation reflexes that produce CN foveation periods requires some minimal foveation interval during which the target image is in the foveal area with low retinal slip velocity and acceleration.

Intermittent oscillopsia in a case of congenital nystagmus. Dependence upon waveform.

Spontaneous reports of oscillopsia are rare in cases of congenital nystagmus (CN). We examined the relationship between nystagmus waveform characteristics and oscillopsia in one such case. To reduce the patient's nystagmus, she was fitted with contact lenses. We examined the effects of tactile feedback by applying local anesthetic while she wore the lenses. When she was without lenses, we provided tactile feedback by applying gentle finger pressure to one eyelid. She was also asked to look at a peripheral afterimage. Nystagmus was analyzed for frequency, amplitude, foveation duration, and drift velocity, if foveation was not perfectly stable. Perceived target stability was recorded. The patient noted oscillopsia during the initial baseline recording and with lid pressure. The image was stable with contact lenses with and without anesthesia and during the second session baseline; at these times, drift velocity was less than 4 degrees/sec and foveation duration was greater than 100 msec. No oscillopsia of the afterimage in dark was noted; she perceived it moving with her gaze as she attempted to look at it. It appears that in some CN patients, the suppression of oscillopsia operates only within fixed limits of foveation stability and duration. When, because of internal or external factors, their nystagmus exceeds these, oscillopsia results.

Latent/manifest latent nystagmus reversal using an ocular prosthesis. Implications for vision and ocular dominance.

Latent/manifest latent nystagmus (LMLN) is a jerk nystagmus with a decreasing-velocity or linear slow phase whose fast phase is in the direction of the fixating eye. Change of the fixating eye by alternating tropias or cover will cause reversal of the LMLN to preserve this relationship. In the dark, where no fixation is possible, the fast phases of LMLN are in the direction of the intended fixating eye; actual visual input will override this effect of intention. A patient with persistent hyperplastic primary vitreous of the right eye, which was enucleated at age 9 due to glaucoma, had LMLN with fast phases to the left. His congenitally blind right eye was replaced with an ocular prosthesis whose movements were conjugate with his seeing eye. In the dark, we found that his LMLN spontaneously reversed as the normally fixating left eye became esotropic. Furthermore, as is the case with LMLN patients who have sight in both eyes, he was able to willfully reverse his LMLN in the dark by alternating his "fixating" eye. We conclude from these observations that the direction of LMLN is determined at a cortical level, is intimately related to the intended fixating eye and that eye "dominance" is predetermined and not altered by visual abnormalities, including blindness.

Catch-up saccade amplitude is related to square wave jerk rate.

Mean catch-up saccade (CUS) amplitude and square wave jerk (SWJ) rate during pursuit were recorded in 20 normal controls, 23 patients with schizophrenia, and 15 patients with affective disorder, using infrared oculography. Target speed during pursuit was 5 degrees/sec. An especially robust correlation was noted in normal controls between SWJ rate during pursuit and mean CUS amplitude (Spearman's rs = 0.87, P less than 0.0001). This correlation also was present in the psychiatric patients (rs = 0.53, P = 0.0006), although it was significantly weaker than in normal controls (P less than 0.02). There were no significant differences between the patient groups regarding the strength of the relationship. Furthermore, similar strong correlations between SWJ rate during fixation and mean CUS amplitude also were found for normals (rs = 0.73, P = .0002) and both patient groups combined (rs = 0.52, P = 0.0009). The results suggest that saccadic intrusions during tracking tax the saccade correcting system, delaying correction for the position error that accumulates when gain is less than 1.0.

Eye movements in Parkinson's disease: before and after pallidotomy.

PURPOSE: To evaluate the effects of unilateral, stereotactic, posteroventral pallidotomy on saccadic eye movements in patients with Parkinson disease (PD). METHODS: Eye movements of 31 patients with moderate to advanced PD were recorded with an infrared system 1 month before and 3 months after pallidotomy. Two kinds of saccade tasks were used: saccade tasks for eliciting visually guided saccades and saccade tasks for eliciting internally mediated saccades (memory-guided, predictive, and anti-saccades). Latency, accuracy, peak velocity, and other parameters of saccades were evaluated. RESULTS: Internally mediated saccades were more impaired in patients with advanced PD compared with those with moderate PD. Pallidotomy did not affect visually guided saccades. After pallidotomy, the peak saccadic velocity of internally mediated saccades decreased. CONCLUSIONS: Hence, although pallidotomy has led to improvements in other motor functions, none were observed in saccadic responses. Rather, several modest decrements, below the level of clinical significance and all in internally mediated saccades, were observed.

Influences of chorion type on saccadic eye movements in twins.

PURPOSE: The influence of genetic and prenatal environmental factors on characteristics of saccadic performance were evaluated in young monozygotic (MZ) twins (8-19 years old) of known chorion type. METHODS: Saccadic eye movements were recorded using an infrared system. Saccadic latency, accuracy, and parameters of amplitude-peak velocity exponential equation (main sequence) were quantified. RESULTS: Intraclass correlations of saccadic parameters differed significantly from zero for monochorionic and dichorionic MZ twins. The within-pair mean squares were significantly less, and intraclass correlations were significantly higher in monochorionic than in dichorionic twins for latency and were similar for other saccadic parameters (accuracy, slope of main sequence, and peak velocity for 15 degrees saccades). CONCLUSIONS: These findings confirmed previous reports that saccadic parameters of MZ twins are significantly correlated and indicated that similarity of these parameters seen in MZ twins may be driven both by genetic and by prenatal environmental factors.

End-point nystagmus.

Infrared oculography was performed during sustained lateral gaze in 12 normal subjects to investigate end-point nystagmus while fixating a target light. Five failed to develop nystagmus despite deviation up to 40 degrees from 4 to 5 min. Six subjects developed nystagmus immediately or shortly after reaching the deviated position. In one, the nystagmus (0.5 degrees to 1 degree and 1.0 Hz) began with only a 20 degree deviation. In another subject, "fatigue" nystagmus developed after 1 min at 30 degrees, and at 35 degrees nystagmus began within 2 sec. One subject developed only fatigue nystagmus, which began after more than 4 min of sustained deviation. In all instances the slow phase had primarily a linear, rather than exponential, waveform.

Smooth pursuit in twins before and after alcohol ingestion.

PURPOSE: The influence of genetic factors on characteristics of smooth pursuit were evaluated in young adult monozygotic (MZ) and dizygotic (DZ) twins before and after the administration of a single dose of ethanol. METHODS: Sinusoidal pursuit was recorded using a scleral search coil at frequencies of 0.25 and 0.5 Hz before and after alcohol consumption. Pursuit gain, interval between saccades, saccadic accuracy, and saccadic amplitude were quantified. RESULTS: Alcohol consumption reduced pursuit gain and saccadic accuracy and increased the rate and amplitude of saccades. Before and after alcohol consumption, the intraclass correlations for MZ twins (rMZ) were highly significant for pursuit gain, interval between saccades, and saccade amplitude. Corresponding correlations for DZ twins (rDZ) were not significant. Heritability values were similar before and after alcohol ingestion. CONCLUSIONS: The disparity between rMZ and rDZ suggests either multiple gene interactions or common environmental influences for MZ twins, greater than those for DZ twins.

Saccadic characteristics of monozygotic and dizygotic twins before and after alcohol administration.

PURPOSE: To evaluate the degree of heritability in the latency, accuracy, and peak velocity of reflexive saccades in young adult monozygotic (MZ) and dizygotic (DZ) twins before and after the administration of a single dose of ethanol. METHODS: Saccades were recorded using a scleral search coil before and after alcohol consumption, and data were analyzed offline. Estimates of heritability based in intraclass correlations (ICCs) and using a maximum likelihood estimates of genetic variance were calculated for the saccadic measures made before and after alcohol, as well as for the changes in latency, accuracy, and velocity. RESULTS: Intraclass correlations for MZ twins (rMZ) were highly significant; those for DZ twins (rDZ) were not significantly different from zero. This disparity between rMZ and rDZ suggests either multiple gene interactions or in utero environmental differences in the MZ twins. Alcohol significantly prolonged latency, reduced accuracy, and lowered peak velocity. Although the changes after alcohol were not significant, heritability values increased in all three measures after alcohol administration. CONCLUSIONS: Latency, accuracy, and peak velocity appear to be controlled by multiple genes or to depend on prenatal environmental factors. Even a single low dose of alcohol appeared to enhance heritability measures. Differences seen between ICCs for latency, accuracy, and velocity after alcohol administration suggest that developmental control of the neural mechanisms underlying each measure may vary.

The nystagmus blockage syndrome. Congenital nystagmus, manifest latent nystagmus, or both?

We have carefully studied, by quantitative oculography, a patient with the nystagmus blockage syndrome (NBS), and two patients with a similar disorder of eye movements that might be mistaken clinically for NBS. Our recordings revealed two distinctly different abnormalities present in a single patient with NBS. Our NBS patient exhibited congenital nystagmus (CN) waveforms when viewing at distance; the CN did not damp with convergence on a near target. When the patient allowed one eye to become esotropic, however, the nystagmus damped considerably and abruptly changed from CN to manifest latent nystagmus (MLN). This peculiar transition from CN to MLN has not been described previously. The appearance of MLN in a case with ongoing CN suggests that two different mechanisms may underlie NBS, since the only other case documented with eye movement recordings showed no transition to MLN. Because the diagnosis of NBS usually is made on evidence of clinical signs alone, it is probable that these two types have been combined indiscriminately and presented as one syndrome. In addition, our discovery of two mechanisms discernable only by quantitative recording suggests that NBS has been diagnosed inappropriately in patients with clinically similar but oculographically different eye signs. Further quantitative studies are required to fully define NBS and to determine if these are the only two mechanisms found in this syndrome.