Impaired Smooth Pursuit Research Articles

Joubert’s syndrome: new cases and review of clinicopathologic correlation

The authors report on seven patients, six males and one female, with Joubert’s syndrome who underwent developmental evaluation, neurologic and ophthalmologic examinations, and magnetic resonance imaging of the brain. All patients had severe developmental delay, hypotonia, impairment of smooth visual pursuit, and saccadic eye movements. Six had jerky eye movements and ptosis was observed in two patients and retinal dystrophy in one. The posterior lobe of the vermis was absent in all patients and the small rudimentary anterior lobe lacked fusion in the midline, with cleft formation in five patients. Malformation of the pontomesencephalic junction, with prominent superior cerebellar peduncles and deep interpeduncular fossa, was observed in all patients. Abnormal cerebellar-brainstem and cerebellocortical connections because of the lack of the posterior vermis and dysplasia of the deep cerebellar nuclei might be responsible for the abnormal eye movements and retarded development in Joubert’s syndrome. Correlation between radiologic findings and clinical symptoms and the possible role of abnormal patterning of the midbrain-hindbrain by homeotic genes during embryonic development are reviewed.

What gives rise to impaired smooth pursuit in the relatives of patients with schizophrenia?

<b>ARCHIVES OF GENERAL PSYCHIATRY</b> <b>Smooth Pursuit Eye Movements to Extraretinal Motion Signals: Deficits in Relatives of Patients With Schizophrenia</b> <i>Gunvant K. Thaker, MD; David E. Ross, MD; Shawn L. Cassady, MD; Helene M. Adami, MSW; David LaPorte, PhD; Deborah R. Medoff, PhD; Adrienne Lahti, MD</i> <h3></h3> <b>Background:</b>Although mounting evidence supports the idea that smooth pursuit abnormality marks the genetic liability to schizophrenia, the precise ocular motor mechanism underlying the abnormality remains unknown. Based on recent findings in schizophrenia, we hypothesize that subtle deficits in the ability to hold online and/or use extraretinal motion information underlie the pursuit abnormality in vulnerable individuals. <b>Methods:</b>The hypothesis was tested in 69 first-degree, biological relatives of probands with schizophrenia; 26 relatives had schizophrenia spectrum personalities (SSP). Subjects recruited from the community (n=71; 29 with SSP), without a known family history of psychosis, constituted the comparison groups. The traditional smooth pursuit gain measure, which is a ratio of smooth pursuit eye velocity in response to both retinal and extraretinal motion signals and the target velocity, was obtained. In addition, newly developed measures of predictive smooth pursuit (ie, in the presence of only extraretinal motion signals) were obtained. The latter measures were evaluated after the current retinal motion signals were made unavailable by briefly making the target invisible. <b>Results:</b>Relatives, particularly those with SSP, showed significantly poorer predictive pursuit, it response to extraretinal motion signals (F_2,130=6.51,<i>P</i>&lt;.005), compared with the community subjects. However, the traditional smooth pursuit gain in response to both retinal and extraretinal motion signals was not different between groups. <b>Conclusions:</b>These results suggest that relatives of patients with schizophrenia, particularly those with SSP, have specific deficits in predictive pursuit based on only extraretinal motion signals. Normal smooth pursuit gain in response to both retinal and extraretinal motion signals is likely due to compensation based on retinal motion information. The latter suggests normal retinal motion processing and smooth pursuit motor output. <i>1998;55:830-836.</i>

Dependence of impaired eye tracking on deficient velocity discrimination in schizophrenia.

Abnormal smooth pursuit eye movements have been found in many schizophrenic patients and in about 40% of their first-degree biological relatives. A velocity discrimination deficit has also been demonstrated in schizophrenic patients. In this study, we address the relation between deficient velocity discrimination and impaired smooth pursuit eye movements, inasmuch as the brain regions responsible for processing velocity signals are implicated in generating and maintaining smooth pursuit. Horizontal eye movements of 15 schizophrenic patients and 8 normal controls were recorded in response to sine wave (predictable) and step-ramp (nonpredictable) targets. Smooth pursuit eye movements were assessed during both the initiation and maintenance periods. Correlations were computed between measures of smooth pursuit (qualitative rating, peak gain, saccade frequency, and initial acceleration) and contrast sensitivity for velocity discrimination. Contrast sensitivity for fine velocity discrimination was significantly correlated both with initial acceleration of smooth pursuit and with peak gain, but was not significantly correlated with saccade frequency and qualitative ratings of pursuit integrity. No significant correlations were found within the normal control group. Deficient processing of velocity information seems to be one component that contributes to a dysfunction in the initiation and maintenance of smooth pursuit in schizophrenia.

Acquired Supranuclear Ocular Motor Paresis Following Cardiovascular Surgery

Acquired supranuclear ocular motor paresis is a rare disorder characterized by impaired saccadic and smooth pursuit eye movements in one or more directions of gaze. Vestibularly induced eye movements, however, are preserved. Six adult patients developed an acquired supranuclear ocular motor paresis following cardiopulmonary bypass surgery. Neuroimaging studies were normal in two patients and were consistent with small vessel ischemia in four patients. The mean cardiopulmonary bypass time was 132.3 min, and mean circulatory arrest time was 38.7 min; these were not outside established norms for this type of surgery. Patients undergoing cardiopulmonary bypass procedures with deep hypothermia are at risk for acquired supranuclear ocular motor paresis, but the development of this syndrome may not be predictable by duration of circulatory arrest or cardiopulmonary bypass times.

Clinical and genetic analysis of three German kindreds with autosomal dominant cerebellar ataxia type I linked to the SCA2 locus.

The detailed clinical, electrophysiological and imaging data of three German autosomal dominant cerebellar ataxia (ADCA) families are reported. Linkage to SCA2 was established using microsatellite markers D12S105, D12S1339(1328), D12S1304(1329) yielding a lod score exceeding +3.0 for the combined data. Analysis of the pedigree data provided evidence of anticipation as observed in other neurodegenerative disorders due to polyglutamine expansion encoded by a CAG repeat. This hypothesis was confirmed by the detection of the SCA2-specific pathological protein using the 1C2 monoclonal antibody which selectively recognizes large polyglutamine expansions and the characterization of a CAG expansion in the patients. Clinically, the families were characterized by progressive ataxia of stance, gait and limbs. Saccade velocity was markedly reduced in SCA2. Further oculomotor findings were gaze palsy, impaired smooth pursuit and reduced optokinetic reflex. Dementia and pyramidal tract signs were rather rare, while peripheral involvement (reduced or absent ankle reflexes, fasciculation-like movements, amyotrophy) was a prominent feature. Electrophysiological investigations provided evidence of sensory neuropathy of the axonal type and degeneration of the posterior columns. Imaging studies demonstrated severe shrinkage of brain-stem structures even in early stages of the disease.

Bilateral Pseudo-internuclear Ophthalmoplegia in Myasthenia gravis

A 38-year-old male with bilateral pseudo-internuclear ophthalmoplegia (-INO) in myasthenia that could have been misdiagnosed as INO in multiple sclerosis is reported. He experienced fluctuating symptoms including double vision, imbalance, and tinnitus. His eye movements simulated bilateral INO, with a downshoot in abduction. After thymectomy, his eye movements became normal. From our case and a review of the literature, we propose that ptosis, downshoot, and fatigability are likely to be signs of pseudo-INO in myasthenia, whereas an impaired vertical smooth pursuit is unlikely. Dissociated nystagmus and monocular overshoot might be the results of central compensation.

Smooth pursuit eye movements in childhood-onset schizophrenia: Comparison with attention-deficit hyperactivity disorder and normal controls

Abnormalities of the smooth pursuit eye movements of adults with schizophrenia have been well described. We examined smooth pursuit eye movements in schizophrenic children, contrasting them with normal and attention-deficit hyperactivity disorder (ADHD) subjects, to determine whether there is continuity of eye movement dysfunction between childhood- and adult-onset forms of schizophrenia. Seventeen schizophrenic children with onset of illness by age 12, 18 ADHD children, and 22 normal children were studied while engaged in a smooth pursuit eye tracking task. Eye tracking variables were compared across the three groups. Schizophrenic children exhibited significantly greater smooth pursuit impairments than either normal or ADHD subjects. Within the schizophrenic group, there were no significant relationships between eye tracking variables and clinical variables, or ventricular/brain ratio. Childhood-onset schizophrenia is associated with a similar pattern of smooth pursuit abnormalities to that seen in later-onset schizophrenia.

Ocular Motor Consequences of Damage to the Abducens Nucleus Area in Humans

A patient with a complete unilateral conjugate gaze paralysis caused by a small lesion affecting the region of the right abducens nucleus, documented by magnetic resonance imaging, is reported. Eye movements were quantitatively evaluated using electro-oculography. A gaze-evoked nystagmus to the contralateral side and impairment of smooth pursuit and vestibular ocular reflex in the contralateral hemifield of movements were found. The differential diagnosis of conjugate gaze paralysis and the additional ocular motor abnormalities are interpreted in light of clinical and experimental findings.

Anticipatory smooth eye movements of high velocity triggered by large target steps: Normal performance and effect of cerebellar degeneration

We studied frequencies and dynamic characteristics of anticipatory smooth eye movements (ASEM) in humans who were tracking step target movements of 20–70 deg amplitude. During presentation of periodic steps of constant amplitude healthy subjects showed frequent high velocity ASEM reaching maximal peak velocities of 5–40 deg/sec. There was no effect of ASEM on the frequency of anticipatory saccades. Randomization of target step amplitude or onset reduced the frequency of ASEM but did not completely abolish fast ASEM. In patients with cerebellar degeneration who exhibited impaired smooth pursuit, fast ASEM were absent and the number of slow ASEM was minimal. In conclusion, large sequential target steps can elicit much higher ASEM velocities than typically described in the literature. Similar to slow ASEM triggered by small steps, these fast ASEM do not require specific training and are not canceled by unpredictable step target motion. However, fast ASEM depend on the intact function of the cerebellum which gives further evidence of their generation by the smooth pursuit oculomotor subsystem.

Antisaccades and smooth pursuit eye movements in schizophrenia

Saccadic and smooth pursuit eye movements were recorded in schizophrenic patients, nonschizophrenic psychiatric patients, and normal controls. Both schizophrenic subjects and psychiatric controls demonstrated greater increases in error rates and greater delays in generating antisaccades than did normal controls. Schizophrenic patients with impaired smooth pursuit tracking showed greater increases in error rates in the antisaccade task than did schizophrenic patients with normal pursuit. Among psychiatric controls, increased errors on the antisaccade task were unrelated to pursuit performance. The small size of this group, however, reduces the power to detect a relation between smooth pursuit tracking and performance on the antisaccade task. Although most patients were receiving one or more medications, some of which can affect eye movements, medication state in this study did not account for differences we report in dependent variables.

Role of pontine nuclei damage in smooth pursuit impairment of progressive supranuclear palsy: a clinical-pathologic study.

We performed a quantitative study of the pontine nuclei in the basis pontis and a semiquantitative study of extrapontine structures involved in smooth pursuit in four patients with severe impairment of horizontal smooth pursuit and histopathologically confirmed diagnosis of progressive supranuclear palsy (PSP). There were only slight changes in the extrapontine structures involved in smooth pursuit, but there was a significant neuronal loss--massive in three patients and mild in one patient--in all nuclei of the basis pontis. Our results suggest that degenerative lesions affecting the pontine nuclei are largely responsible for the horizontal smooth pursuit impairment in PSP.

Saccade and Smooth-Pursuit Impairment after Cerebral Hemispheric Lesions

A number of cortical and subcortical areas are involved in the control of saccades and smooth pursuit, and lesions affecting these areas result in various ocular motor syndromes. Most of these syndromes are relatively subtle and have to be ascertained using recordings, because other brain areas may largely take over the function of a damaged area. Anterior cortical, posterior cortical, large and bilateral cortical, subcortical and degenerative cerebral lesions are successively reviewed. In the anterior part of the cerebral hemisphere, the frontal eye field (FEF), supplementary eye field (SEF) and prefrontal cortex (PFC), i.e. area 46 of Brodmann, control eye movements. The FEF appears to be principally involved in the control of intentional saccades, in particular those made with a retinotopic reference system, and in smooth pursuit. The SEF could control saccades made with a spatiotopic reference system, and sequences of saccades (requiring a temporal working memory). The PFC could control the inhibition of unwanted reflexive saccades, and be involved in spatial memory used for programming all types of memory-guided saccades. In the posterior part of the cerebral hemisphere, the parietal eye field (PEF) is involved in the triggering of reflexive visually guided saccades, and the middle temporal (MT) and medial superior temporal (MST) areas in smooth pursuit. Acute and large unilateral lesions usually result in transitory ipsilateral conjugate eye deviation. Bilateral lesions affecting both the FEF and the PEF result in severe saccade and smooth-pursuit paresis, whereas bilateral posterior temporoparietal lesions result in Balint's syndrome, consisting of both eye movement and visual-attention abnormalities. Subcortical lesions also result in various eye movement abnormalities, which have been little documented to date. Lastly, degenerative cerebral diseases, such as Alzheimer's disease, Parkinson's disease, Huntington's disease, progressive supranuclear palsy and corticobasal degeneration result in more or less severe eye movement disturbances. Eye movement recordings may contribute to early differential diagnosis of some of these degenerative diseases.

前庭刺激による感覚認知障害を認めたＡｄｒｅｎｏｌｅｕｋｏｄｙｓｔｒｏｐｈｙ症例

The central pathways for the subjective sensation of “turning” and nystagmus are different even though both rely on the same basic input. Thus a lesion of the primary vestibular projection area of the cerebral cortex could induce the phenomenon of the loss of subjective vestibular sensation during vestibular stimulation. This report describes a right handed 35-year-old male with adrenoleukodystrophy, who initially complained of hearing and visual disturbance and showed the vestibular agnosia. MRI showed sub-cortical lesions in the parietal, temporal and occipital areas. The main lesion was in the white matter, especially on the right side (non-dominant hemisphere).Neurological examination showed auditory agnosia and slight visual agnosia. Deep sensation was also impaired in both upper and lower exthemities, presumably because of cortical lesions. Neurotological examination revealed impaired smooth pursuit, optokinetic nystagmus and voluntary saccades. These abnormal eye movements suggested a parietal or occipital cortex disorder on the non-dominant side. Because a brain stem lesion could be ruled out “nystagmus-sensation dissociation”, which was observed during caloric tests in this case, was considered to be caused by a pure cortical lesion. This phenomenon appeared to be part of the “vestibular agnosia” caused by a lesion of the primary sensory cortex of vestibular sensation.

Express Saccades and Smooth Pursuit Eye Movement Function in Schizophrenic, Affective Disorder, and Normal Subjects

Abstract Saccadic and smooth pursuit eye movements were recorded in three groups of subjects: a schizophrenic group, a non-schizophrenic psychotic patient comparison group, and a normal control group. Schizophrenic subjects demonstrated a greater decrease in saccadic response time than did normal controls in a gap task (when the fixation point was turned off 150 msec before the target appeared). The psychiatric comparison subjects did not differ from normal controls. Further, only schizophrenic subjects demonstrated a relation between smooth pursuit and saccadic eye movement performance, such that subjects with impaired smooth pursuit showed a larger decrease in saccadic response time in the gap task. The relation between performance on the gap task and quality of smooth pursuit and its relevance for a prefrontal deficit hypothesis of schizophrenia are discussed.

Retinotopic and directional deficits of smooth pursuit initiation after posterior cerebral hemispheric lesions.

We investigated the initiation of ocular smooth pursuit with horizontal ramp targets in 16 patients with unilateral posterior cerebral lesions. Four of the 16 patients had directional pursuit asymmetry, in which smooth eye movement velocities were reduced toward the lesion, independent of target location on the retina. Of seven patients with normal visual fields for the target, two had a retinotopic eye movement deficit consisting of impaired smooth pursuit of targets moving in both horizontal directions in the hemifield contralateral to their lesion. Patients with retinotopic deficits and normal visual fields, and those with directional deficits, had impairment of smooth pursuit similar to that caused by unilateral lesions of cortical areas MT (middle temporal) and MST (medial superior temporal) in monkeys. All but one patient with either of these defects had a lesion near the junction of Brodmann's areas 19, 37, and 39, providing evidence that this region includes the human homologues of monkey areas MT and MST. One patient with a retinotopic pursuit defect and normal visual fields had a lesion of the rostral superior temporal sulcus, which may have included the homologue of the superior temporal polysensory area of monkeys.

Optokinetic-vestibular interaction in patients with increased gain of the vestibulo-ocular reflex.

We studied optokinetic nystagmus (OKN), optokinetic afternystagmus (OKAN) and visual-vestibular interaction in five patients with markedly elevated vestibulo-ocular reflex (VOR) gain due to cerebellar atrophy. All had impaired smooth pursuit, decreased initial slow phase velocity of OKN, and impaired ability to suppress the VOR with real or imagined targets. OKN slow phase velocity gradually built up over 25-45 s, reaching normal values for low stimulus velocities (< or = 30 deg/s). Initial velocity of OKAN was increased, but the rate of decay of OKAN was normal. These findings can be explained by models that include separate velocity storage and variable gain elements shared by the vestibular and optokinetic systems.

Evidence of impaired smooth pursuit eye movement performance in crack cocaine users

A recent single photon emission computed tomography (SPECT) brain imaging study of heavy cocaine abusers in their second week of abstinence reported a high frequency of focal perfusion abnormalities involving inferoparietal, temporal, and anterofrontal cortices and basal ganglia (Holman et al 1991). As the brain areas with perfusion detects described in this SPECT study are regarded as important in mediating various voluntary eye movements (Leichnetz and Goldberg 1988), the fbllowing study was carried out to compare the smooth pursuit eye movement (SPEM) performance of cocaine-dependent individuals to the SPEM performance of patients with schizophrenia as well as a population of normal subjects. Measurable SPEM disturbance is quite common in schizophrenia (Clementz and Sweeney 1990).

Asymmetric smooth pursuit impairment and nystagmus in motor neurone disease

Eye movements were recorded using infrared oculography in 17 patients with motor neurone disease (MND) and in 17 age-matched controls. Major findings were a marked reduction in pursuit gain for the severely affected patient group as target speed increased from 10 deg/sec to 20 deg/sec and asymmetric pursuit (leftward gain lower than rightward) in these patients. The authors’ study illustrates the effect of MND on the central pathways of the nervous system which control eye movements and shows that an association may exist between specific ocular motor defects and severity.

Clinical Pharmacology of Lamotrigine

The pharmacokinetics and pharmacodynamics of lamotrigine (LTG), a new antiepileptic drug (AED), were studied in healthy volunteers. In an open dose-escalating study, LTG 240 mg produced peak plasma concentrations of around 3 micrograms/mg with no significant adverse events. Subsequent pharmacokinetic studies revealed complete oral absorption, first-order kinetics with a mean half-life of approximately 1 day, and elimination mainly as a glucuronide in the urine. Early studies in patients with epilepsy revealed more rapid metabolism when given with enzyme-inducing AEDs and delayed metabolism by valproate. A placebo-controlled, double-blind study compared LTG 120 and 240 mg with phenytoin (PHT) 500 and 1,000 mg, and diazepam (DZP) 10 mg. Visual analogue scales showed sedation after PHT 1,000 mg and DZP 10 mg, but not after LTG. Smooth pursuit eye movements and adaptive tracking were impaired by DZP and PHT 1,000 mg. LTG did not affect these variables. A comparison of LTG 150 and 300 mg and carbamazepine (CBZ) 200, 400, and 600 mg demonstrated impairment of smooth pursuit and saccadic eye movements by CBZ 600 and 400 mg, but not by LTG. Additionally, CBZ 600 mg impaired adaptive tracking and increased body sway and heart rate. These studies have shown LTG to have desirable and predictable pharmacokinetic properties for an AED. Pharmacodynamic effects were absent, suggesting a high therapeutic index.

Abnormal visual-vestibular interaction and smooth pursuit tracking in psychosis: implications for cerebellar involvement.

The vestibulo-ocular response to caloric irrigation and the effect of vestibular activation on eye movements were examined during light and dark testing conditions--the latter to assess these measures under conditions attenuating possible cerebellar-vestibular interaction present in the light-adapting condition. Subjects were psychiatric patients (23 actively-ill psychotic patients and 23 remitted psychotic patients) and normal controls (23 with no history of psychiatric illness). Standardized clinical electronystagmographic procedures were used, together with electrographic measures to assess visual fixation and level of arousal. During the light condition previous findings of impaired smooth pursuit tracking and reduced fixation suppression in actively psychotic patients were replicated. These patients also exhibited hyperresponsive vestibulo-ocular responses. Remitted patients' performance levels on test measures fell between those of controls and actively-ill patients on the majority of response measures. However, remitted patients were found to have impaired smooth pursuit tracking and failure of fixation suppression relative to controls. The dark testing condition effected a normalization of several patient-control differences, including smooth pursuit tracking and the elimination of vestibular hyperresponsiveness. In many respects the present results parallel findings of eye movement aberrations in cerebellar patients. These similarities include evidence of an intact but hyperresponsive vestibular system, the normalization of previously disordered pursuit tracking during dark-testing, the failure of fixation suppression, and the decrease in this measure during dark conditions. These findings suggest that cerebellar dysfunction may contribute to irregularities in smooth pursuit tracking and fixation suppression found in psychotic patients.