Bedside and electro-oculographic analysis of abnormal ocular movements in spinocerebellar degenerations: effects of thyrotropin-releasing hormone

We studied ocular movements in 130 patients with spinocerebellar degenerations. Patients had blurred vision (33.3%), diplopia (40.2%), oscillopsia (18.6%), ocular flutter (22.3%), rebound nystagmus (25.4%), square-wave jerks, (29.2%), macro square-wave jerks (6.2%), and macro saccadic oscillations (10.8%). Electro-oculographic abnormalities included reduction of saccadic velocity, dysmetria, and saccadic smooth pursuit. All the abnormal movements were improved by the injection of thyrotropin-releasing hormone.     

Disorders in cerebellar ocular motor control. I. Saccadic overshoot dysmetria. An oculographic, control system and clinico-anatomical analysis.

Photoelectric eye movement recording in 9 patients with cerebellar disorders defined three features of saccadic overshoot dysmetria: (i) saccades were hypermetric and successively diminished in amplitude; (ii) saccadic initiation interval averaged 173 ms: and (iii) eye position was constant during the intersaccadic period. These characteristics indicated that the visually evoked saccades subserving foveation had increased gain, and were modelled by computer simulations using a sampled-data control model with increased feed-forward gain. Eight patients with saccadic overshoot dysmetria had cerebellar neoplasms, vermis-splitting surgical procedures and mid-line cerebellar signs. This clinical evidence suggests that vermian dysfunction is responsible for saccadic overshoot dysmetria. Normally, the cerebellar vermis appears to play an adaptive role by continuously adjusting gain of the direct visual motor pathway. When cerebellar disorder exists, adaptive gain modulation is lost, and, if gain then increases, saccadic overshoot dysmetria is a result.     

Internally and externally guided voluntary saccades in unmedicated and medicated schizophrenic patients. Part I. Saccadic velocity

Saccadic eye movements were elicited in 30 schizophrenic patients before and in 17 of these 30 during antipsychotic treatment with neuroleptics, and compared with those of 12 age-matched controls under three different conditions: (a) the gap paradigm, which tests the visually triggered and visually guided saccades; (b) the anti-task paradigm, which tests the internally guided, visually triggered saccades; and (c) the memory paradigm, which tests the internally triggered and guided saccades. Eye movements were recorded by DC electro-oculography, and the peak eye velocities for the different saccades were calculated. We found that antipsychotic treatment with neuroleptics reduces the peak saccadic eye velocity. This effect is larger for internally guided saccades than for externally triggered and guided eye movements. The saccadic velocity of the unmedicated schizophrenic patients did not differ from that of the controls. Since patients with diseases of the basal ganglia primarily show abnormalities of the internally guided and triggered saccades, our findings indicate that neuroleptics influence the oculomotor loop through the basal ganglia and that this loop, by means of neuroleptic influence on the brainstem saccadic burst generator, also influences the peak velocity of the internally guided saccades. This contradicts the current idea of the role of the cortical input to the brainstem saccadic burst generator, which is thought to not be involved in the determination of saccadic velocity. Received: 20 December 1997 / Accepted: 15 September 1998     

Eye-hand coordination in essential tremor.

Patients with essential tremor (ET) or with cerebellar lesions have in common oculomotor abnormalities, with the exception of saccadic eye movements, which do not seem to be involved in ET. Since grasping is prolonged in ET and might be related to saccadic dysmetria, we tested whether simultaneous hand pointing could unmask it. Twelve ET patients and 14 controls performed saccades with and without simultaneous pointing movements to the same targets, and with and without a gap between the disappearance of the fixation point and the appearance of the target. Eye movements were recorded with the magnetic search-coil method, hand movements with an ultrasound-emitting probe. ET patients did not have saccadic dysmetria, and contrary to normal subjects their saccadic latency did not decrease during combined eye-hand movements compared with saccades performed in isolation. Hand movements had a longer duration in ET patients, with decreased peak acceleration, an increased latency of the peak velocity, and peak deceleration. In conclusion, this first study on eye-hand coordination in ET revealed abnormal kinematic changes in the early phase of pointing movements. These changes might be related to cerebellar disease but they are independent of the intention tremor component and saccade performance.     

Visually and memory guided saccades in a case of cerebellar saccadic dysmetria.

Saccades under four specific test conditions (visually guided, visually remembered, vestibular remembered, and cervical remembered) were studied in a 38 year old man with ocular dysmetria due to an angioma of the dorsal cerebellar vermis. The aim of the study was to investigate if the saccadic disorder was specific to certain subsets of saccades elicited by different sensory modalities. The experiments showed that initial saccades were equally hypermetric in all four conditions and that final eye position was normal in all memory guided saccade tests. Eye movements differed after the initial saccade, however. Whereas corrective saccades were seen in most visually guided and visually remembered experiments, postsaccadic centripetal drifts were documented in non-visual (vestibular and cervical) remembered saccades. These results indicate that the cerebellar vermis modulates the amplitude of the initial saccade (pulse size of saccadic innervation) independently of the saccadic task. The finding that post-saccadic drift never occurred when saccades were programmed using visual positional information suggests that the dorsal vermis may participate in the process of pulse step integration of saccades elicited by memorised vestibulo-cervical information.     

Neurology of eye movements]

Eye movements are necessary for clear and stable vision, for which images of the world should be brought to the fovea and be held steady on the retina. The main types of eye movements consist of saccadic eye movements, vergence, vestibular eye movements, smooth pursuit eye movements and eye movements for visual stabilization. Saccades are fast eye movements and have consistent relationship between their peak velocity and the size of the movements. The burst neurons in the brainstem are the generator of saccades and receive projections from the frontal eye field, supplementary eye field, parietal eye field, basal ganglia, superior colliculus and cerebellum. Saccades are evaluated by a speed and accuracy of the size. There are different types of saccade, such as visually triggered saccades, antisaccades, memory-guided saccade and predictive saccades. The specific test paradigms of saccades may show the localization and the type of diseases. Opsoclonus, flatter-like oscillation, ocular myoclonus, square-wave jerks are characteristic involuntary eye movements. Syndromes of the paramedic pontine reticular formation, medial longitudinal fascicules and one-and-a-half syndrome are caused by disease of the pons.     

Saccade onset and offset lambda waves: relation to pattern movement visually evoked potentials

The lambda (lambda) wave is an occipital EEG potential which occurs when saccadic eye movements are made against an illuminated contrast background. There is some disagreement concerning the presence of sub-components to the lambda-wave, and its relationship to visually evoked potentials. In the present study, lambda-waves were recorded with saccades of different durations (30-110 ms) and compared to VEPs associated with pattern movements of similar durations and velocity. It was found that the lambda-wave consisted of a saccade onset component with positive sub-components at 59 and 100 ms after saccade onset, and a saccade offset component with a positive potential at 74 ms after saccade offset. With small saccades of 30 ms duration or less, these components superimposed to form a single lambda-wave. In the case of pattern movement VEPs, a movement onset component of latency 110 ms following movement onset, and a movement offset component at 89 ms after movement offset, were identified. The similar behaviour of the lambda-wave and VEP under these conditions supports the view that the lambda-wave is a visually evoked potential resulting from movement of the visual field across the retina during a saccadic eye movement.     

Macro square wave jerks in a rhesus monkey: physiological and anatomical findings in a case of selective impairment of attentive fixation

An otherwise normal female rhesus monkey executed large saccadic eye movements (macro square wave jerks) when required to attentively fixate a small visual target (fixation point). The jerks were observed exclusively in this specific testing situation. They occurred periodically at a frequency of 2.04 + - 0.18 Hz to the right side with an amplitude of 23.5 deg. Direction of the jerks was about 3-4 degrees downward from horizontal. These parameters remained constant throughout the several months of daily recording. No jerks were executed during periods when the behaviourally important target was absent or substituted by another, behaviourally non-relevant visual stimulus. The monkey could perform normal visually guided saccades as well as smooth pursuit eye movements, but with the jerks always superimposed, when the monkey paid attention to the visual target. Histologic inspection of the brain revealed the presence of an incapsulated nematode in the cortex of lobulus simplex of the right cerebellar hemisphere, i.e., in a region involved in oculomotor control.     

Disturbed smooth pursuit and saccadic eye movements in schizophrenia

Smooth pursuit and saccadic eye movements of schizophrenic patients were examined. In a pendulum (0.5 Hz) tracking task schizophrenic inpatients had a slightly lower smooth pursuit gain than outpatients and controls, who showed no significant differences. The number of saccades, counter-saccades and velocity arrests occurring in a 20 s tracking epoque was the same in patients and controls, but patients made larger saccades. When tracking a stepping target by saccadic eye movements, schizophrenic inpatients, and to a lesser extent outpatients, exhibited longer reaction times than controls and had a higher incidence of "non-fixation" (saccades away from the target while the target is stationary). Schizophrenic patients also showed a significantly larger proportion of dysmetric saccades (undershooting the target). While similar changes of reaction time and non-fixation score were observed in manic-depressives and alcoholics, dysmetria was more often found in schizophrenics and possibly constitutes the expression of a specific impairment of attention.     

Saccadic eye movements in psychiatric patients

Saccadic eye movements were examined in 110 psychiatric patients and 26 controls, evaluating three parameters, the frequency of dysmetric saccades, nonfixation and the saccadic reaction time. Dysmetric saccades (dysmetria) were defined as saccadic reactions undershooting the target, nonfixation was defined as a deviation of the gaze from the target with the target stationary. While the nonfixation score and the saccadic reaction time were slightly increased in most of the psychiatric patient groups as compared to controls, an increase of the dysmetria score was confined to patients with schizophrenic and schizoaffective disorders. Dysmetria is thus interpreted as the expression of a relatively specific impairment of attention in these patients.     

The nucleus pontis centralis caudalis in Huntington's disease

Slow saccadic eye movements occur in some patients with Huntington's disease (HD), and minor defects of supranuclear eye movement control can be demonstrated in the majority by neuroophthalmological laboratory methods. In the pathogenesis of slowed saccades, a lesion of the paramedian pontine reticular formation and specifically the nucleus pontis centralis caudalis was considered likely due to similar eye movement disturbances in well documented degenerative and vascular lesions of the lower pontine tegmentum. A systematic morphometric study was performed on the nucleus pontis centralis caudalis in 9 patients with HD. Two of them had grossly defective saccades during life, and 7 had normal eye movements on routine examination. In 8 patients, the nucleus was reduced in size, revealed a higher than normal neuronal density, and a striking loss of large neurons. One patient with HD and normal morphometric results had died 2 years after the onset of chorea from an unrelated illness. It is proposed that the nucleus pontis centralis caudalis is regularly affected in HD and that progressive loss of large neurons is the cause of saccadic slowing.     

Ocular motor disorders in mitochondrial encephalopathy with lactic acid and stroke-like episodes with the 3271 (T-C) point mutation in mitochondrial DNA.

BACKGROUND: Ocular motor function can provide insights into areas of dysfunction within the nervous system. There are no published eye movement recordings in patients with mitochondrial encephalopathy with lactic acid and stroke-like episodes (MELAS). Our purpose in this study was to analyze the ocular motor features of a family with MELAS with a (T-C) mutation at nucleotide position 3271 in the mitochondrial tRNA-Leu gene. METHODS: The search coil method was used to record visually-guided saccades, antisaccades, and triangular pursuit tasks in the horizontal and vertical planes in three patients in a Japanese family with MELAS. RESULTS: The patients showed saccadic dysmetria and prolonged saccadic reaction times, deficits in the ability to suppress reflex eye movements, and increased reaction time during antisaccades, downbeat nystagmus, square wave jerks, and impairment in pursuit. CONCLUSIONS: On the basis of eye movement recordings, patients with MELAS have frontal cortex as well as cerebellar dysfunction.     

Microstimulation of the primate cerebellar vermis during saccadic eye movements

The cerebellar vermal cortex in monkey was electrically stimulated through a microelectrode with brief pulse strains synchronized to the onset of selected saccadic eye movements. The delivery of these intrasaccadic microstimuli were randomly interposed in groups of saccadic eye movements made by trained monkeys to known target locations. The trajectory of the saccades with intrasaccadic stimuli were then compared to those made to the same target without stimulation. Contralaterally directed saccades were consistently slowed from their normal trajectory (normally at 12 ms after stimulus onset) and were made hypometric. Ipsilaterally directed saccades were not affected. Vertical eye movement components were also affected at some stimulating sites. Changing the stimulus train duration from 10 to 80 ms had no effect on the change in velocity or amount of dysmetria produced in contralateral saccades. Taken together these results suggest that a different set of cerebellar elements were being stimulated by the intrasaccadic mode as contrasted to stimulation at the same site at random times. Furthermore, the short period of time during an ongoing saccade presents a unique instant in which to test the relationship of various central structures to the saccadic system. Based on current concepts of the organization of the brainstem saccadic pulse generators, these data are interpreted to suggest that: (1) the cerebellar vermis has a rather direct influence on the contralateral saccade generator, (2) this influence can act to recode (diminish) the generator's representation of the size of motor error, (3) the effect occurs at a point in the generator where motor error is spatially coded.     

Myoclonus and ocular oscillations induced by L-tryptophan

A patient with chronic manic-depressive illness developed generalized myoclonus and spontaneous ocular oscillations after a single 2 gm dose of L -tryptophan. She had been pretreated with both a tricyclic antidepressant and a monoamine oxidase inhibitor. The involuntary movements gradually disappeared within 24 hours after the drugs were discontinued. Electrooculographic recording 7 hours after onset of the abnormal eye movements revealed square-wave jerks and hypometric voluntary saccades. Pursuit as well as optokinetic and vestibular slow phases were normal except for superimposition of the square-wave jerks. Repeat recording 24 hours later was entirely normal.     

Unilateral pallidotomy for Parkinson's disease disrupts ocular fixation.

Although some motor functions of the basal ganglia have been well studied, the oculomotor functions are not well established. We studied eye movements in patients with Parkinson's disease (PD) undergoing pallidotomy to assess the role of the globus pallidus interna (GPi) in oculomotor control. Horizontal visually guided, gap and predictive saccades as well as ocular fixation were studied in patients with advanced PD before and 1 month after unilateral pallidotomy, and in healthy controls on two occasions 1 month apart. There was no difference in saccadic latency or accuracy, the number of saccadic anticipations or the ability to generate predictive saccades between the two assessments for either patients or controls. The number and amplitude of square wave jerks during ocular fixation however increased significantly in patients after pallidotomy. The results imply altered function of frontal or prefrontal cortical regions involved in ocular fixation resulting from a disruption to inhibitory pallidal influences on thalamocortical projections. The posteroventral GPi however appears not to be involved in externally controlled or predictive saccadic function.     

Square wave jerks in children and adolescents

Square wave jerks are involuntary, horizontal, saccadic intrusions that interrupt fixation. Each square wave jerk consists of an initial saccade that moves the fovea away from the intended position of fixation, followed by a second saccade in the opposite direction, which refoveates the fixation position. Square wave jerks reportedly occur in 24-60% of healthy adults. No previous study of square wave jerks in children and adolescents is available. We recorded eye movements using an infrared eye tracker in 38 participants aged 8-19 years while they fixated on a visual target for 1 minute. The frequency of square wave jerks, and the durations, amplitudes, and peak velocities of their saccades, were calculated and correlated with age. Ninety percent of participants had square wave jerks. Their median frequency was 3 per minute (range, 1-18), median duration was 249 milliseconds, the median amplitude of their saccades was 0.81 degrees, and the median peak velocity was 60 degrees/second. No parameter of square wave jerks correlated with age. The prevalence of square wave jerks is high in children and adolescents. This finding may be a feature of the less mature brain, and may reflect an inability to suppress unwanted supranuclear triggers for saccades.     

SPEM impairment in drug-naive schizophrenic patients: evidence for a trait marker.

Smooth-pursuit eye movements (SPEM) were assessed in healthy subjects and in drug-naive, chronic, and residual schizophrenic patients. SPEM gain was found to be decreased in all the schizophrenic patients who also exhibited a significant increase in the rate of saccades. The frequency of square-wave jerks was the same in schizophrenic patients and normal controls, suggesting that the primary abnormality in schizophrenic patients was a low gain rather than a defect of the saccadic system. Patients were retested 1 month later, and stability of gain was high even in formerly drug-naive subjects who had been treated for 1 month with neuroleptic drugs. Altogether these results confirm the conclusions of most previous studies, extend them to drug-naive schizophrenic patients, and favor the hypothesis that SPEM impairment is a trait marker in schizophrenia.     

Disturbed smooth pursuit and saccadic eye movements in schizophrenia

Summary Smooth pursuit and saccadic eye movements of schizophrenic patients were examined. In a pendulum (0.5 Hz) tracking task schizophrenic inpatients had a slightly lower smooth pursuit gain than outpatients and controls, who showed no significant differences. The number of saccades, counter-saccades and velocity arrests occuring in a 20 s tracking epoque was the same in patients and controls, but patients made larger saccades. When tracking a stepping target by saccadic eye movements, schizophrenic inpatients, and to a lesser extent outpatients, exhibited longer reaction times than controls and had a higher incidence of non-fixation (saccades away from the target while the target is stationary). Schizophrenic patients also showed a significantly larger proportion of dysmetric saccades (undershooting the target). While similar changes of reaction time and non-fixation score were observed in manic-depressives and alcoholics, dysmetria was more often found in schizophrenics and possibly constitutes the expression of a specific impairment of attention.     

The effects of tobacco smoking on smooth pursuit eye movements

It has recently been shown that tobacco smoking in normal human subjects induces a transient primary-position upbeat nystagmus. We studied the effects of tobacco smoking on smooth pursuit eye movements and found defects in both vertical and horizontal tracking during the first 5 minutes after smoking one cigarette. The smooth pursuit defect consisted of a reduction in upward tracking velocity and the superposition of saccadic square-wave jerks on both vertical and horizontal tracking eye movements. The degree of impairment in upward smooth pursuit correlated with the intensity of tobacco-induced nystagmus present when recording in darkness. We suggest that these alterations are due to summation of nystagmus on normal tracking eye movements rather than primary defects in the smooth pursuit system.     

Oculomotor disorders in Huntington''s chorea.

Electro-oculographic recordings were obtained from 11 patients with Huntington's disease. Significant reduction of saccadic velocity was constantly found. In all the patients vertical saccades were much more impaired than horizontal. When present, vertical saccades showed long latency, low amplitude, low velocity, and disturbances related to blinking. Following movements were jerky, and ability to perform repeated rhythmic movements was impaired. These results are in agreement with previous observations and underline the selective defect of rapid movements as a characteristic feature of Huntington's disease. Further, they suggest a possible correlation between the difficulty in performing repeated ocular movements and the impaired execution of gestural sequences involving a succession of different fundamental movements.