Search

The objective of this study was to characterize saccades in children with neurodevelopmental disorders (NDDG, 17 children, age: 7–12 years) and compare them with a control group (CG, 15 children, age: 7–12 years), comparing the outcomes obtained with a subjective score system (Northeastern State University College of Optometry’s Oculomotor test, NSUCO) with the objective analysis obtained through a commercially available Eye Tracker (Tobii Eye X, Tobii, Stockholm, Sweden) and a specialized software analysis (Thomson Software Solutions, Welham Green, UK). Children from the NDDG obtained significantly lower NSUCO scores (p &lt, 0.001) compared with CG. Concerning eye tracking analyses, we found a significantly higher number of hypometric saccades in NDGG (p ≤ 0.044). Likewise, we found a significantly higher percentage of regressions in the NDDG for a time interval of presentation of stimuli of 1 s (p = 0.012). Significant correlations were found between different NSUCO scores and percentage of regressions, number of saccades completed and number of hypometric saccades. The presence of hypometric saccades and regressions seems to be a differential characteristic sign of children with neurodevelopmental disorders that can be detected using an objective eye tracking analysis, but also using the subjective test NSUCO that can be easily implemented in all clinical settings.

Purpose Ocular motor abnormalities such as abnormal saccades are common in idiopathic Parkinson's disease (PD) and atypical parkinsonian syndrome, such as progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). In this study, we describe a case of patient with PD and show a video illustrating severe delay of reflexive saccades. Observations A 68-year-old Caucasian woman with diagnosis of PD presented for evaluation of diplopia. Neuro-ophthalmic examination revealed good visual acuity in both eyes and normal optic nerves but prominent ocular motor abnormalities, including hypometric saccades, impaired smooth pursuit, and convergence insufficiency causing diplopia at near. Despite treatment with carbidopa-levodopa three times per day, she exhibited episodic, severe delay of reflexive saccades. During these episodes, the patient appeared frozen and unable to initiate reflexive saccades for 20 s or longer. This freezing of reflexive saccades was variable and occurred suddenly during exam but could be interrupted by smooth pursuit. There was no gait freezing, eyelid apraxia, or prominent exacerbation of other motor symptoms. Freezing of saccades dramatically resolved after increasing dosage of carbidopa-levodopa. Conclusions and Importance We describe a patient with dopa-responsive parkinsonian syndrome with intermittent difficulty initiating reflexive saccades mimicking ocular motor apraxia. Resolution of saccadic freezing with higher carbidopa-levodopa is consistent with ocular motor impairment as a result of degeneration and dysfunction of the dopaminergic pathways in supranuclear ocular motor control.

Background SYNE1 ataxia is an autosomal recessive hereditary condition, the main characteristic features of which are gait and limb ataxia and cerebellar dysarthria. Reports have revealed that the clinical phenotype of SYNE1 ataxia is more complex than the first published cases with pure cerebellar signs indicated. The aim of this study was to characterize eye movement alterations in the first diagnosed Hungarian SYNE1 ataxia patients. Results Saccades and antisaccades were examined with an eye tracker device in 3 SYNE1 (one patient has two frameshift mutations [c.8515_8516insA, p.Met2839Asnfs*53 and c.11594_11595insG, p.Glu3866*] in a compound heterozygous state, whereas two subjects have a splicing variant [c.23146-2A > G] in a homozygous state), 6 Friedreich ataxia (FA) patients and 12 healthy controls. Besides that, detailed clinical phenotyping and comprehensive neuropsychological assessment were carried out in all patients with ataxia. In addition to the characteristic cerebellar alterations, pyramidal signs and polyneuropathy were observed at least in 2 SYNE1 ataxia patients, for which no other underlying reason was found. The eye tracking assessment revealed hypometric saccades in the longer amplitude (18.4°) saccadic paradigm in all SYNE1 patients, whereas 2 out of 3 SYNE1 subjects performed slow saccades as well. In the antisaccade task, higher incorrect ratios of antisaccades were demonstrated in SYNE1 patients compared to healthy controls, showing inverse correlation with working memory test results. The corresponding data of FA patients was dispersed over a wide range, partially overlapping with control data. Conclusions The current study draws attention to the presence of eye movement disorders in patients with SYNE1 ataxia and demonstrates that alterations in the antisaccade paradigm may be related to working memory deficits.

Abnormal eye movements are commonly observed in movement disorders. Ocular motility examination should include bedside evaluation and laboratory recording of ocular misalignment, involuntary eye movements, including nystagmus and saccadic intrusions/oscillations, triggered nystagmus, saccades, smooth pursuit (SP), and the vestibulo-ocular reflex. Patients with Parkinson’s disease (PD) mostly show hypometric saccades, especially for the self-paced saccades, and impaired SP. Early vertical saccadic palsy is characteristic of progressive supranuclear palsy-Richardson’s syndrome. Patients with cortico-basal syndrome typically show a delayed onset of saccades. Downbeat and gaze-evoked nystagmus and hypermetric saccades are characteristic ocular motor findings in ataxic disorders due to cerebellar dysfunction. In this review, we discuss various ocular motor findings in movement disorders, including PD and related disorders, ataxic syndromes, and hyperkinetic movement disorders. Systemic evaluation of the ocular motor functions may provide valuable information for early detection and monitoring of movement disorders, despite an overlap in the abnormal eye movements among different movement disorders.

Objective To show that eye movement abnormalities differ between essential tremor (ET) and tremor dominant Parkinson’s disease (PD-T), and that these abnormalities reflect cerebellar dysfunction in ET and basal ganglia pathology in PD-T. Methods In this exploratory study, in 23 patients with ET, 21 age-matched patients with PD-T, and 19 age-matched healthy controls (HCs), we investigated visually guided saccades, antisaccades, and smooth pursuit eye movements (SPEM). Results While the ET group had a normal gain (saccade amplitude/target amplitude) and latency of saccades, the PD-T group had hypometric visually guided saccades, and a prolonged latency of visually guided saccades and antisaccades. The SPEM gain was similarly low in both ET and PD-T and was significantly lower in both patient groups than in the HC group. Conclusions In ET, SPEM gain was reduced in the presence of normal saccades, whereas in PD-T, the reduced SPEM gain was accompanied by delayed saccade initiation and hypometric saccades, in line with cerebellar dysfunction in ET and basal ganglia dysfunction in PD-T. Significance These findings support the presumed cerebellar pathology in ET. In addition, the difference in saccade features may contribute to the groundwork for a quantitative diagnostic test to differentiate between these disorders.

Eye movement examination may be used to rapidly differentiate peripheral and central vestibular syndromes in patients with acute unsteadiness. The analysis of oculomotor impairments may also support the accurate localization of cerebral lesions, particularly those in the brainstem, that are often loosely defined by cerebral MRIs. Saccades, smooth pursuit, and nystagmus were recorded with video-oculography in a patient who had developed sudden vertigo as a consequence of a focal lesion in the depth of the brachium pontis. The patient had shown a previously unreported pattern of eye movement impairments consisting of (i) ipsilesional hypometric saccades, (ii) contralesional saccadic smooth pursuit, and (iii) unilateral gaze-evoked nystagmus. These symptoms enabled the precise localization of the trajectory of pontocerebellar saccadic tracts in the depth of the brachium pontis. We propose that this rare association resulted from a disruption of cerebellar afferents of saccadic pathways and of cerebellar efferents of horizontal smooth pursuit pathways. This reported case emphasizes the crucial role of careful bedside oculomotor examination in order to discriminate between peripheral and central vestibular syndromes in the diagnosis of sudden vertigo. Moreover, it reveals an exceptional pattern of oculomotor impairments that may allow for the precise localization of the trajectory of cerebellar saccadic afferent pathways in the depth of the brachium pontis.

International audience; Whether the recessive ataxias, Ataxia with oculomotor apraxia type 1 (AOA1) and 2 (AOA2) and Ataxia telangiectasia (AT), can be distinguished by video-oculography and alpha-fetoprotein level remains unknown. We compared 40 patients with AOA1, AOA2 and AT, consecutively referred between 2008 and 2015 with 17 healthy subjects. Video-oculography revealed constant impairments in patients such as cerebellar signs, altered fixation, impaired pursuit, hypometric saccades and abnormal antisaccades. Horizontal saccade latencies could be highly increased reflecting oculomotor apraxia in one third of patients. Specific distinctive alpha-fetoprotein thresholds were determined for AOA1 (7-15 \textmug/L), AOA2 (15-65 \textmug/L) and AT (\textgreater65 \textmug/L). Early age onset, severe walking disability, movement disorders, sensori-motor neuropathy and cerebellar atrophy were all shared. In conclusion, alpha-fetoprotein level seems to permit a distinction while video-oculography does not and therefore is not mandatory, even if an appropriate oculomotor examination remains crucial. Our findings are that AOA1, AOA2 and AT form a particular group characterized by ataxia with complex oculomotor disturbances and elevated AFP for which the final diagnosis is relying on genetic analysis. These findings could guide genetic analysis, assist reverse-phenotyping and provide background for the interpretation of the numerous variants of unknown significance provided by next-generation sequencing.

A previously healthy 72-year-old man presented with 1 year of progressive ataxia and slurred speech. There was no notable family history and no history of alcohol abuse or neurotropic drug use. Examination showed bilateral hypometric saccades, a 2–3 Hz palatal tremor with face and neck involvement, and truncal ataxia (video at [Neurology.org/cp][1]). There was no pendular nystagmus. MRI brain 6 months after the onset of symptoms showed high signal abnormality in the inferior olivary nuclei of the anterior medulla and mild superior vermal atrophy (figure, A and B). His clinical presentation and neuroimaging were consistent with a diagnosis of progressive ataxia and palatal tremor (PAPT), a rare idiopathic neurodegenerative disease with bulbar features, palatal tremor, and cerebellar ataxia. PAPT imaging features include a typical hypertrophic olivary appearance on MRI, sometimes with cerebellar degeneration.1,2 [1]: http://cp.neurology.org/lookup/doi/10.1212/CPJ.0000000000000298

Background Symptoms of psychosis in schizophrenia reflect disturbances in sense of agency—difficulty distinguishing internally from externally generated sensory and perceptual experiences. One theory attributes these anomalies to a disruption in corollary discharge (CD), an internal copy of generated motor commands used to distinguish self-movement–generated sensations from externally generated stimulation. Methods We used a transsaccadic shift detection paradigm to examine possible deficits in CD and sense of agency based on the ability to perceive visual changes in 31 schizophrenia patients (SZPs) and 31 healthy control subjects. We derived perceptual measures based on manual responses indicating the transsaccadic target shift direction. We also developed a distance-from-unity-line measure to quantify use of CD versus purely sensory (visual) information in evaluating visual changes in the environment after an eye movement. Results SZPs had higher perceptual thresholds in detecting shift of target location than healthy control subjects, regardless of movement direction or amplitude. Despite producing similar hypometric saccades, healthy control subjects overestimated target location, whereas SZPs relied more on the experienced visual error and consequently underestimated the target position. We show that in SZPs the postsaccadic judgment of the initial target location was largely aligned with the measure based only on visual error, suggesting a deficit in the use of CD. This CD deficit also correlated with positive schizophrenia symptoms and disturbances in sense of agency. Conclusions These results provide a novel approach in quantifying abnormal use of CD in SZPs and provide a framework to distinguish deficits in sensory processing versus defects in the internal CD-based monitoring of movement.

The evolution of the fovea centralis, the most central part of the retina and the area of the highest visual accuracy, requires humans to shift their gaze rapidly (saccades) to bring some object of interest within the visual field onto the fovea. In addition, humans are equipped with the ability to rotate the eye ball continuously in a highly predicting manner (smooth pursuit) to hold a moving target steadily upon the retina. The functional deficits in neurodegenerative movement disorders (e.g., Parkinsonian syndromes) involve the basal ganglia that are critical in all aspects of movement control. Moreover, neocortical structures, the cerebellum, and the midbrain may become affected by the pathological process. A broad spectrum of eye movement alterations may result, comprising smooth pursuit disturbance (e.g., interrupting saccades), saccadic dysfunction (e.g., hypometric saccades), and abnormal attempted fixation (e.g., pathological nystagmus and square wave jerks). On clinical grounds, videooculography is a sensitive noninvasivein vivotechnique to classify oculomotion function alterations. Eye movements are a valuable window into the integrity of central nervous system structures and their changes in defined neurodegenerative conditions, that is, the oculomotor nuclei in the brainstem together with their directly activating supranuclear centers and the basal ganglia as well as cortical areas of higher cognitive control of attention.

Ataxia with oculomotor apraxia type 2 (AOA2) is one of the most frequent autosomal recessive cerebellar ataxias. Oculomotor apraxia refers to horizontal gaze failure due to deficits in voluntary/reactive eye movements. These deficits can manifest as increased latency and/or hypometria of saccades with a staircase pattern and are frequently associated with compensatory head thrust movements. Oculomotor disturbances associated with AOA2 have been poorly studied mainly because the diagnosis of oculomotor apraxia was based on the presence of compensatory head thrusts. The aim of this study was to characterise the nature of horizontal gaze failure in patients with AOA2 and to demonstrate oculomotor apraxia even in the absence of head thrusts. Five patients with AOA2, without head thrusts, were tested in saccadic tasks with the head restrained or free to move and their performance was compared to a group of six healthy participants. The most salient deficit of the patients was saccadic hypometria with a typical staircase pattern. Saccade latency in the patients was longer than controls only for memory-guided saccades. In the head-free condition, head movements were delayed relative to the eye and their amplitude and velocity were strongly reduced compared to controls. Our study emphasises that in AOA2, hypometric saccades with a staircase pattern are a more reliable sign of oculomotor apraxia than head thrust movements. In addition, the variety of eye and head movements' deficits suggests that, although the main neural degeneration in AOA2 affects the cerebellum, this disease affects other structures.

International audience; When saccade amplitude becomes systematically inaccurate, adaptation mechanisms gradually decrease or increase it until accurate saccade targeting is recovered. Adaptiveshortening and adaptive lengthening of saccade amplitude rely on separate mechanisms in adults. When these adaptation mechanisms emerge during development is poorlyknown except that adaptive shortening processes are functional in children above 8 years of age. Yet, saccades in infants are consistently inaccurate (hypometric)as if adaptation mechanisms were not fully functional in early childhood. Here, we tested reactive saccade adaptation in 10–41 month-old children compared to agroup of 20–30 year-old adults. A visual target representing a cartoon character appeared at successive and unpredictable locations 10◦ apart on a computer screen.During the eye movement toward the target, it systematically stepped in the direction opposite to the saccade to induce an adaptive shortening of saccade amplitude(Experiment 1). In Experiment 2, the target stepped in the same direction as the ongoing saccade to induce an adaptive lengthening of saccade amplitude. In bothbackward and forward adaptation experiments, saccade adaptation was compared to a control condition where there was no intrasaccadic target step. Analysis of baselineperformance revealed both longer saccade reaction times and hypometric saccades in children compared to adults. In both experiments, children on average showedgradual changes in saccade amplitude consistent with the systematic intrasaccadic target steps. Moreover, the amount of amplitude change was similar between childrenand adults for both backward and forward adaptation. Finally, adaptation abilities in our child group were not related to age. Overall the results suggest that theneural mechanisms underlying reactive saccade adaptation are in place early during development.

PURPOSE Spinocerebellar ataxias type 2 and 28 (SCA2, SCA28) are autosomal dominant disorders characterized by progressive cerebellar and oculomotor abnormalities. We aimed to investigate cerebellar, brainstem, and extraocular muscle involvement in the mitochondrial SCA28 disease compared with SCA2. METHODS We obtained orbital and brain 1.5 T-magnetic resonance images (MRI) in eight SCA28 subjects, nine SCA2, and nine age-matched healthy subjects. Automated segmentation of cerebellum and frontal lobe was performed using Freesurfer software. Manual segmentations for midbrain, pons, and extraocular muscles were performed using OsiriX. RESULTS Eye movement abnormalities in SCA2 subjects were characterized by slow horizontal saccades. Subjects with SCA28 variably presented hypometric saccades, saccadic horizontal pursuit, impaired horizontal gaze holding, and superior eyelid ptosis. Quantitative brain MRI demonstrated that cerebellar and pons volumes were significantly reduced in both SCA2 and SCA28 subjects compared with controls (P < 0.03), and in SCA2 subjects compared with SCA28 (P < 0.01). Midbrain and frontal lobe volumes were also significantly reduced in SCA2 compared to controls (P < 0.03), whereas these volumes did not differ between SCA2 and SCA28 and between SCA28 and control subjects. The extraocular muscle areas were 37% to 48% smaller in SCA28 subjects compared with controls (P < 0.002), and 14% to 36% smaller compared with SCA2 subjects (P < 0.03). Extraocular muscle areas did not differ between SCA2 and controls. CONCLUSIONS Our MRI findings support the hypothesis of different cerebellar and extraocular myopathic contributions in the eye movement abnormalities in SCA2 and SCA28 diseases. In SCA28, a myopathic defect selectively involving the extraocular muscles supports a specific impairment of mitochondrial energy metabolism.

Here we present a case in which exome sequencing rapidly produced a molecular diagnosis for a patient with hypomyelinating leukodystrophy, for whom years of costly conventional testing had not identified a molecular diagnosis. The patient had severe developmental delay, ataxia, nystagmus, external opthalmoplegia, hypometric saccades, and high myopia. Magnetic resonance imaging of the brain demonstrated severe failure of myelination of the corona radiate and centrum semi ovale. Through exome sequencing, two novel heterozygous missense variants were identified in the POLR3A gene (c.1160C . G; p.Ala387Gly and c.3781G . A; p.Glu1261 Lys). We propose the use of exome sequencing for the diagnosis of genetically heterogeneous conditions such as hypomyelinating leukodystrophy as a cost-effective primary diagnostic tool.

Background/aims Visually guided saccades and gaze-fixation ability were recorded in patients with early Parkinson9s disease (PD). Methods Magnetic search coil system was used to measure horizontal and vertical eye positions. Results ‘Staircase’ visually guided saccades (multiple hypometric saccades separated by an intersaccadic interval) and ‘staircase’ square-wave jerks (SWJ) were present in all patients. The SWJ amplitude (total amplitude of the series of hypometric saccades comprising the SWJ) was abnormally large (mean 2°). SWJ frequency was also abnormally high (50–70 intrusions/min). Conclusion Loss of dopaminergic neurons in the substantia nigra pars compacta leading to phasic excitation of the substantia nigra pars reticulata and, in turn, phasic inhibition of the superior colliculus (SC), may account for ‘staircase’ visually guided saccades in these patients. This mechanism, however, does not explain abnormally large SWJ, which in the traditional view results from decreased inhibition upon SC. The abnormally large SWJ could be due to a compensatory increase in frontal eye field activity secondary to the increased inhibition upon the SC. Abnormally large and frequent SWJ are often used clinically to distinguish multi-system atrophy from idiopathic PD. Our study, however, suggests that idiopathic PD cannot be excluded if the patient has large-amplitude SWJ.

Objectives:Parkin gene mutations are the most common cause of early-onset parkinsonism. Patients with Parkin mutations may be clinically indistinguishable from patients with idiopathic early-onset Parkinson disease (EOPD) without Parkin mutations. Eye movement disorders have been shown to differentiate parkinsonian syndromes, but have never been systematically studied in Parkin mutation carriers.Methods: Eye movements were recorded in symptomatic (n = 9) and asymptomatic Parkin mutation carriers (n = 13), patients with idiopathic EOPD (n = 14), and age-matched control subjects (n = 27) during established oculomotor tasks.Results: Both patients with EOPD and symptomatic Parkin mutation carriers showed hypometric prosaccades toward visual stimuli, as well as deficits in suppressing reflexive saccades toward unintended targets (antisaccade task). When directing gaze toward memorized target positions, patients with EOPD exhibited hypometric saccades, whereas symptomatic Parkin mutation carriers showed normal saccades. In contrast to patients with EOPD, the symptomatic Parkin mutation carriers showed impaired tracking of a moving target (reduced smooth pursuit gain). The asymptomatic Parkin mutation carriers did not differ from healthy control subjects in any of the tasks.Conclusions: Although clinically similarly affected, symptomatic Parkin mutation carriers and patients with idiopathic EOPD differed in several oculomotor tasks. This finding may point to distinct anatomic structures underlying either condition: dysfunctions of cortical areas involved in smooth pursuit (V5, frontal eye field) in Parkin-linked parkinsonism vs greater impairment of basal ganglia circuits in idiopathic Parkinson disease.

Aman in his 70s presented with a 20-year history of progressive ataxia and an8-month history of “spasms” in his throat. Hewas initiallybelieved tohavecerebellardegenerationdue toalcohol abuse. However, his difficultywith gait progressedafter cessationof alcohol use. The reported throat spasms did not affect his ability to speak or eat. Examination revealed hypometric saccades, truncal and limb ataxia, and decreased vibratory sensewith an inability to ambulate. Bradykinesia and mild rigidity were also noted. Palatal myoclonus was seen at a frequency of 1 to 2 Hz (Video). Severe cerebralandcerebellaratrophywasdemonstratedonmagnetic resonance imaging of the brain (Figure). Results of testing for spinocerebellar ataxia types 1, 2, 3, 6, and 12 were normal.

Patients with Parkinson's disease (PD) present with eye movement disturbances that accompany the cardinal motor symptoms. Previous studies have consistently found evidence that large-scale functional networks are critically involved in eye movement control. We challenged the hypothesis that altered eye movement control in patients with PD is closely related to alterations of whole-brain functional connectivity in association with the neurodegenerative process. Saccadic and pursuit eye movements by video-oculography and 'resting-state' functional MRI (3 Tesla) were recorded from 53 subjects, i.e. 31 patients with PD and 22 matched healthy controls. Video-oculographically, a broad spectrum of eye movement impairments was demonstrated in PD patients vs. controls, including interrupted smooth pursuit, hypometric saccades, and a high distractibility in anti-saccades. Significant correlations between altered oculomotor parameters and functional connectivity measures were observed, i.e. the worse the oculomotor performance was, the more the regional functional connectivity in cortical, limbic, thalamic, cerebellar, and brainstem areas was decreased. Remarkably, decreased connectivity between major nodes of the default mode network was tightly correlated with the prevalence of saccadic intrusions as a measure for distractability. In conclusion, dysfunctional eye movement control in PD seems to be primarily associated with (cortical) executive deficits, rather than being related to the ponto-cerebellar circuits or the oculomotor brainstem nuclei. Worsened eye movement performance together with the potential pathophysiological substrate of decreased intrinsic functional connectivity in predominantly oculomotor-associated cerebral functional networks may constitute a behavioral marker in PD.

In an eye movement countermanding paradigm it is demonstrated for the first time that a tactile stimulus can be an effective stop signal when human participants are to inhibit saccades to a visual target. Estimated stop signal processing times were 90-140 ms, comparable to results with auditory stop signals, but shorter than those commonly found for manual responses. Two of the three participants significantly slowed their reactions in expectation of the stop signal as revealed by a control experiment without stop signals. All participants produced slower responses in the shortest stop signal delay condition than predicted by the race model (Logan and Cowan 1984) along with hypometric saccades on stop failure trials, suggesting that the race model may need to be elaborated to include some component of interaction of stop and go signal processing.

In a stop signal paradigm to investigate the control of human saccades subjects were instructed to make a saccade to a visual target appearing suddenly l5° to the left or to the right of the fixation point. In 25% of the trials an auditory stop signal was presented after a variable delay that required the subject to inhibit the saccade. The stop signal was presented randomly at the target position, at the opposite side, or at fixation. Using different estimation techniques the average time needed to inhibit a saccade (stop signal processing time, or SSPT) was estimated on the basis of the race model. The SSPT estimates ranging from 50 to 100 ms (depending on subject) are shorter than those from previous studies with visual stop signals. Position of the auditory stop signal did not show an effect on countermanding effectiveness. We found saccadic response times consistent with the race model predictions for two subjects, while a third subject showed small but consistent violations. Moreover, all subjects showed a tendency towards hypometric saccades for responses that could not be inhibited. These findings are discussed with respect to recent neurophysiological results. © 2001 Elsevier Science Ltd. All rights reserved.

The objective was to describe in multiple sclerosis, a cerebellar eye movement syndrome that resulted from an acute episode of inflammatory demyelination. Contrapulsion is an ocular motor disturbance characterised by a triad of (1) hypermetric saccadic eye movements in a direction opposite from a precisely localised lesion within a specific white matter pathway, the uncinate fasciculus, at the level of the superior cerebellar peduncle (SCP); (2) hypometric saccades towards the side of the lesion; (3) oblique saccades directed away from the side of the lesion on attempted vertical saccades. Infrared oculography was used to demonstrate the characteristic features of contrapulsion in two patients with multiple sclerosis. Brain MRI showed lesions within the region of the uncinate fasciculus and superior cerebellar peduncle in both patients. Eye movement recordings showed saccadic hypermetria away from the side of the lesion and saccadic hypometria towards the side of the lesion. The hypometria decomposed into a series of stepwise movements as the eye approached the target. Oblique saccades directed away from the side of the lesion were seen on attempted vertical saccades. In conclusion, ocular contrapulsion can be seen in patients with multiple sclerosis and results from a lesion in the region of the SCP, involving the uncinate fasciculus.

Eight patients suffering from primary cerebellar degenerative diseases undertook a walkway task, demanding precise foot placement at each step, and a visual fixation task, requiring only eye movements. Step cycle and horizontal eye movements were recorded throughout the tasks and compared to those of healthy adults (including age- and sex-matched controls). Cerebellar patients displayed both locomotor and oculomotor deficits. Increases in duration of the stance, swing and double support phases of the step cycle were all shown to contribute to ataxic gait. Dysmetric saccades to fixate the footfall targets were seen more frequently in patients than in controls. These hypometric saccades were followed by one or more corrective saccades (patients: >45% accompanied by one or more corrective saccades; controls

Visually-guided saccades of 21 offspring of schizophrenic parents and 21 individually matched controls were compared with regard to the frequency of occurrence of saccadic hypometria and hypermetria, non-fixations, and omissions of target jumps. Target steps ranged from 10 to 60 degrees, and interstimulus intervals averaged 2.5 s; subjects were promised financial reward depending on performance. Recordings were carried out at the subjects' homes. To screen for cognitive abilities and psychopathological behavior, subjects were tested by means of an intelligence scale and a behavioral checklist. With large target steps (40-60 degrees), the high-risk group made significantly more grossly hypometric saccades (gain < or = 0.8) than the control group; responses to small target steps (10-30 degrees) exhibited a similar, albeit statistically not significant, trend. There were no significant differences with regard to the occurrence of hypermetria. Non-fixations scored marginally higher in the high-risks as compared to controls, but this was again not a significant difference. The incidence of omissions of saccades was very low in both groups. The results of the study suggest that subjects at genetic risk for schizophrenia may differ from controls by an increased incidence of conspicuously hypometric saccades. Clearly, this difference is not caused by a deficit of the saccadic motor circuitry proper; comparison to control data obtained with a similar experimental protocol suggests that it probably reflects an impaired internal control of saccades in the presence of distraction and stress. The relevance of saccades as indicators of a possible schizophrenic vulnerability is discussed.

We studied the clinical features and molecular genetics of a family, afflicted with a form of atypical parkinsonism, originating from the Madeira Islands of Portugal. We examined four affected individuals and reviewed clinical information on one other affected family member. Mean age at onset was 31 years. Parkinsonism (akinesia, rigidity, gait disturbance) was the most prominent feature in advanced disease. Levodopa responsiveness with peak-dose dyskinesia was present in one individual. Initial symptoms and other clinical features were variable and included other extrapyramidal signs (dystonia, action tremor of the limbs and bulbar muscles, synkinesis), ophthalmologic abnormalities (ptosis, slow saccades, progressive external ophthalmoplegia, hypometric saccades, saccadic pursuit movements), speech abnormalities (dysarthria, hypernasality), cortical impairment (dementia, frontal lobe dysfunction, palilalia, persevera-tion), minor cerebellar signs (dysmetria, gait ataxia), pyramidal abnormalities (spasticity, hyperreflexia), and peripheral nervous system abnormalities (propioceptive loss, areflexia, distal weakness, atrophy). The length of trinucleotide repeats in the MJD1 gene was in the normal range for all affected individuals.

This article concerns the neural mechanisms that underlie short-term saccadic adaptation in the rhesus monkey. By means of a consistent intrasaccadic target displacement, the relation between visual input and motor output was gradually changed in three monkeys, such that they made hypometric saccades. During this process, the activity of saccade-related burst neurons in the intermediate and deep layers of the Superior Colliculus (SC) was recorded in two of the monkeys. Our findings show that, like in humans, only saccades evoked within a restricted field around the adaptation target were adapted. However, unlike in humans, the kinematic properties of adapted saccades also changed systematically during the adaptation process. Typically, adapted saccades were slower and had a longer duration than would be expected on the basis of the main sequence for nonadapted visually guided movements. During adaptation, saccade-related activity of units in the SC remained appropriate for the saccade that was required to foveate the initial target, rather than for the saccade that was actually made. This means that adaptation caused a dissociation between SC activity and the ensuing saccade. Thus, the activity of the colliculus was better described in “required eye displacement coordinates” than in “actual eye displacement coordinates.” Our data provide further evidence for the hypothesis that short-term saccadic adaptation acts at a level downstream from the SC, presumably at a stage that determines the kinematics of saccadic eye movements.

The oculomotor vermis (lobulus VI, VII) and its immediate output structure, the caudal part of the fastigial nucleus (fastigial oculomotor region, FOR), participate in the generation of saccades and smooth pursuit eye movements. Lesions to these cerebellar midline structures lead to step-size error dysmetria, with saccades to visual targets being either too large (hypermetric) or too small (hypometric). Smooth pursuit eye movements can have a reduced gain (cogwheel smooth pursuit).An analysis of lesion data in humans and monkeys revealsI. Lesions to the oculomotor vermis have the opposite effect to lesions of the FOR. Whereas a unilateral oculomotor vermis lesion causes hypometric ipsilateral and hypermetric contralateral saccades, FOR lesions lead to hypometric contralateral and hypermetric ipsilateral saccades. Furthermore, bilateral oculomotor vermis lesions lead to hypometric saccades, and bilateral FOR lesions to hypermetric saccades.2. Saccade and smooth pursuit disorders are related. Hypometric sac...

Saccadic averaging that causes subjects' gaze to land between the location of two targets when faced with simultaneously or sequentially presented stimuli has been often used as a probe to investigate the nature of computations that transform sensory representations into an oculomotor plan. Since saccadic movements involve at least two processing stages—a visual stage that selects a target and a movement stage that prepares the response—saccade averaging can either occur due to interference in visual processing or movement planning. By having human subjects perform two versions of a saccadic double-step task, in which the stimuli remained the same, but different instructions were provided (REDIRECT gaze to the later-appearing target vs. FOLLOW the sequence of targets in their order of appearance), we tested two alternative hypotheses. If saccade averaging were due to visual processing alone, the pattern of saccade averaging is expected to remain the same across task conditions. However, whereas subjects produced averaged saccades between two targets in the FOLLOW condition, they produced hypometric saccades in the direction of the initial target in the REDIRECT condition, suggesting that the interaction between competing movement plans produces saccade averaging.

1. To test whether the cerebellum is involved in compensating for orbital nonlinearities, we recorded discharges of saccadic burst neurons in the fastigial oculomotor region (FOR) during both centrifugal and centripetal saccades in two trained macaque monkeys. 2. We also investigated the metrics of centrifugal and centripetal saccades with the same amplitude while output signals from the fastigial nucleus were blocked by muscimol, an agonist of inhibitory neurotransmitter gamma-aminobutyric acid (GABA), injected into the FOR. 3. We studied discharges of 32 fastigial neurons that were inhibited by microstimulation of the oculomotor vermis. These neurons exhibited unique burst responses during contralaterally and ipsilaterally directed saccades, as shown in our previous report. The discharge pattern, the peak burst frequency, the burst lead time, and the burst duration were consistent, regardless of initial eye position. 4. The muscimol injection produced hypermetric saccades toward the injection side and hypometric saccades to the opposite side, regardless of whether saccade was centripetally or centrifugally directed. 5. These findings suggest that the FOR is not involved in the compensation of saccade metrics for orbital nonlinearities.

Saccadic accuracy requires that the control signal sent to the motor neurons must be the right size to bring the fovea to the target, whatever the initial position of the eyes (and corresponding state of the eye muscles). Clinical and experimental evidence indicates that the basic machinery for generating saccadic eye movements, located in the brainstem, is not accurate: learning to make accurate saccades requires cerebellar circuitry located in the posterior vermis and fastigial nucleus. How do these two circuits interact to achieve adaptive control of saccades? A model of this interaction is described, based on Kawato's principle of feedback-error-learning. Its three components were (1) a simple controller with no knowledge of initial eye position, corresponding to the superior colliculus; (2) Robinson's internal feedback model of the saccadic burst generator, corresponding to preoculomotor areas in the brain-stem; and (3) Albus's Cerebellar Model Arithmetic Computer (CMK), a neural net model of the cerebellum. The connections between these components were (I) the simple feedback controller passed a (usually inaccurate) command to the pulse generator, and (2) a copy of this command to the CMAC; (3) the CMAC combined the copy with information about initial eye position to (4) alter the gain on the pulse generator's internal feedback loop, thereby adjusting the size of burst sent to the motor neurons. (5) If the saccade were inaccurate, an error signal from the feedback controller adjusted the weights in the CMAC. It was proposed that connection (2) corresponds to the mossy fiber projection from superior colliculus to oculomotor vermis via the nucleus reticularis tegmenti pontis, and connection (5) to the climbing fiber projection from superior colliculus to the oculomotor vermis via the inferior olive. Plausible initialization values were chosen so that the system produced hypometric saccades (as do human infants) at the start of learning, and position-dependent hypermetric saccades when the cerebellum was removed. Simulations for horizontal eye movements showed that accurate saccades from any starting position could be learned rapidly, even if the error signal conveyed only whether the initial saccade were too large or too small. In subsequent tests the model adapted realistically both to simulated weakening of the eye muscles, and to intrasaccadic displacement of the target, thereby mimicking saccadic plasticity in adults. The architecture of the model may therefore offer a functional explanation of hitherto mysterious tectocerebellar projections, and a framework for investigating in greater detail how the cerebellum adaptively controls saccadic accuracy.

The cerebellum is implicated in maintaining the saccadic subsystem efficient for vision by minimizing movement inaccuracy and by learning from endpoint errors. This ability is often disrupted in degenerative cerebellar diseases, as demonstrated by saccade kinetic abnormalities. The study of saccades in these patients may therefore provide insights into the neural substrate underlying saccadic motor control. We investigated the different extent of saccade dynamic abnormalities in spinocerebellar ataxia type 2 and late-onset cerebellar ataxias, genetically undefined and with prevalent cerebellar atrophy. Reflexive and voluntary saccades of different amplitude (10°-18°) were studied in seven patients with spinocerebellar ataxia 2, eight patients with late-onset cerebellar ataxia and 25 healthy controls. Quantitative analysis of saccade parameters and measures of saccade accuracy were performed. Detailed neurological, neurophysiological and magnetic resonance imaging assessment was obtained for each patient. Genetic and laboratory screening for spinocerebellar ataxias and other forms of late-onset cerebellar ataxias were also performed. A lower peak saccade velocity and longer duration was observed in patients with spinocerebellar ataxia 2 with respect to those with late-onset cerebellar ataxia and controls. Unlike subjects with spinocerebellar ataxia 2, patients with late-onset cerebellar ataxia showed main sequence relationships to similar saccades made by normal subjects. Saccades were significantly more inaccurate, namely hypometric, in late-onset cerebellar ataxia than in spinocerebellar ataxia 2 and inaccuracy increased with saccade amplitude. The percentage of hypometric primary saccades and of larger secondary corrective saccades were consistently higher in late-onset cerebellar ataxia than in spinocerebellar ataxia 2 and controls. No other significant differences were found between groups. Two different mechanisms were adopted to redirect the fovea as fast and/or accurately as possible to peripheral targets by the two groups of cerebellar patients. Patients with spinocerebellar ataxia 2 maintained accuracy using slow saccades with longer duration. This reflects prevalent degenerative processes affecting the pontine burst generator and leading to saccade velocity failure. On the other hand, patients with late-onset cerebellar ataxia reached the target with a number of fast inaccurate, mostly hypometric saccades. Different degrees of cerebellar oculomotor vermis involvement may account for differences in optimizing the trade-off between velocity and accuracy in the two groups. In addition, as suggested by spinocerebellar patients having slow saccades that are no longer ballistic, visual feedback might be continuously available during the movement execution to guide the eye to its target.

Saccadic dysmetria is seen in patients with cerebellar diseases as well as in monkeys whose vermis and fastigial nucleus are experimentally lesioned. We investigated the oculomotor signs of the vermis by blocking cerebellar impulses with bicuculline injections into the fastigial nucleus. The oculomotor abnormalities associated with the bicuculline treatment (in effect, functional as well as reversible, unilateral decortication of the vermis) were hypometric saccades toward the injection side and gaze deviation toward the opposite side. These oculomotor signs disappeared with the withdrawal of the bicuculline effect.

This study examined the effect of attention in young infants on the saccadic localization of peripheral stimuli. Infants ranging in age from 5 to 14 weeks were tested using a peripheral stimulus detection paradigm. The presence of a central fixation stimulus decreased detection probability, particularly if attention was engaged with the central stimulus. Peripheral stimulus localization usually was accomplished with a single eye movement. When localization was accomplished by multiple eye movements, corrective saccades occurred most frequently and fixed-amplitude hypometric saccades occurred less frequently. A decrease in the slope of the linear component of the main sequence was found from 5 to 11 weeks of age, and this decrease was independent of attention.

PURPOSE. To investigate saccade dynamics as a function of age to determine whether they follow the pattern of development and decline predicted by Weale's model of aging. METHODS. One hundred ninety-five participants between the ages of 3 and 86 years made visually guided horizontal prosaccades ranging in size from 1° to 60° in response to dot stimuli. Eye movements were recorded binocularly with a video-based eye tracker, sampling at 120 Hz. Saccadic latency, accuracy, and velocity were measured and analyzed as a function of age. RESULTS. Mean saccadic latency decreased from 439 ms at 3 years to 172 ms at 14 years, followed by a period of relative stability to age 50 and finally, gradually increased to 264 ms at ≥80 years. For saccadic accuracy (amplitude gain), there was a statistically significant (P < 0.05) interaction between saccade size and age. Participants made increasingly hypometric saccades as age and saccade size increased. Average age group saccadic asymptotic peak velocity (v max ) increased during childhood from 446 deg/s at age 3, to a peak of 610 deg/s at 14 years and then gradually declined with age to approximately 345 deg/s for participants ≥80 years. CONCLUSIONS. Age affected saccadic latency, accuracy, and velocity. For each parameter there was a different pattern of development and decline probably related to the way in which the portion of the brain that controls each function develops and ages.

We report on a 50-year-old woman who presented with an 8-year history of involuntary movements, unsteadiness, and cognitive decline. Examination revealed multidomain cognitive deficits, jerky ocular pursuit movements, hypometric saccades, gaze impersistence, dysarthria, upper limb dystonia, and widespread chorea. TATA-binding protein gene test revealed trinucleotide expansion allele sizes of 47 and 39 repeats, confirming the diagnosis of spinocerebellar ataxia type 17 (SCA-17). Magnetic resonance imaging (MRI) showed marked cerebellar atrophy and putaminal rim hyperintensity. This is the first case of SCA-17 reported to show MRI signal change in the basal ganglia, and extends the phenotypic manifestation of SCA-17.

Four patients suffering from primary cerebellar degeneration and healthy matched controls undertook a test of functional mobility that demanded precise foot placement at each step. Vertical and horizontal eye movements were measured (using a head mounted eye tracking system) together with footfall patterns. Healthy subjects stepped accurately onto all targets and produced a clear pattern of saccadic eye movements, fixating each target in the sequence just prior to footlift. Still video frames, showing direction of gaze while walking, provide direct visual confirmation that these saccades serve to transfer gaze between successive targets in the walkway sequence. The planning of the saccade to the next target probably provides the locomotor control system with information useful for planning the corresponding (and shortly following) step. Cerebellar patients showed characteristic locomotor and oculomotor deficits. Dysmetric saccades to fixate footfall targets were seen in 39% of steps. Analysis confirms that these multi-saccadic eye movements include an initial hypometric saccade, which undershoots the target, followed by one or more additional saccades in the same direction. Direct visualisation of gaze at the end of a saccadic sequence confirms that these additional saccades are indeed corrective resulting in a foveal image of the footfall target.

To investigate the brain stem control of saccadic eye movements, the paramedian pontine reticular formation (PPRF) in rhesus monkeys was temporarily and partially inactivated with the local anesthetic lidocaine. The influence on ipsilesional, contralesional, and upward saccades was examined. While the effects of the inactivation on contralesional and upward saccades were inconsistent and small, consistent and marked modifications were observed for ipsilesional movements. For ipsilesional, horizontal saccades, all lidocaine injections caused a decrease in peak velocity and a proportional increase in duration, which substantially altered the shape of the velocity profile. The rise in duration usually fell short of preventing hypometric saccades at the peak of the effect. However, as the lidocaine effect dissipated, the amplitude often returned to control, even though the velocity and duration remained compromised. For ipsilesional, oblique saccades, the effect of lidocaine on the horizontal component was similar to that for horizontal saccades. The vertical component of oblique saccades was also influenced, albeit to a much lesser extent: the duration of the vertical component typically increased, while the vertical peak velocity either decreased or exhibited no significant change. These results were compared with simulations of three prominent models for cross-coupling oblique saccades. In general, these results of the temporary inactivation of PPRF are consistent with the predictions of local feedback models for saccadic control.

Oculomotor dysfunction in Parkinson's disease (PD) is mainly characterized by a fragmentation of memory-guided gaze shifts (target is reached by several hypometric saccades). Since this phenomenon can also be observed in normal subjects, we scrutinized its pathophysiological significance in PD patients. We recorded horizontal eye movements in eleven mildly- or moderately-affected PD patients and eleven control subjects. A quantitative assessment of gaze shift fragmentation was made possible by increasing its incidence over a sequence of two visually- and two subsequent memory-guided gaze shifts. Basic saccade measures (latency, velocity, etc.) were similar in the two subject groups as well as in fragmented versus non-fragmented gaze shifts. Fragmentation probability is increased in the second memory-guided gaze shift, and this clearly more so in patients than in controls. The fragmentation shows a typical gain pattern (uniform increase of gain of saccadic amplitudes across correction saccades towards 1.0 with the last saccade of the gaze shift) independent of subject group, stimulus mode, and fragmentation degree. Gaze shift fragmentation represents a physiological phenomenon, which has thus far been overlooked. It reflects a robust correction mechanism, which assures that target is reached even if the pre-oculomotor drive through the basal ganglia to the superior colliculus becomes abnormally weak or under inadequately strong inhibition – as is postulated for PD. Thus, only the abnormally high incidence of fragmentation, and of the associated amplitude reduction of the primary saccades, rather than the phenomenon per se, can be used as a diagnostic criterion in early stages of PD.

Schizophrenic patients and their relatives exhibit a genetically increased probability of impaired smooth pursuit eye movements (Levy et al. 1993). It is less clear whether also saccadic eye movements are affected. Abnormalities such as hypometric tracking of target steps or saccadic intrusions during fixation have been reported by some groups (e.g., Cegalis et al. 1982; Mather and Putchat 1983) and denied by others (e.g., Yee et al. 1987). A number of studies considering both patients and their first degree relatives, which were carried out by our group either in a hospital environment or at the patients’ or their relatives’ homes, demonstrated an increased rate of hypometric saccades (gain < 0.75) of up to 35% as compared to about half that rate (18%) in controls (Schreiber et al. 1995, 1997). However, a hypometria incidence of 18% in controls is much higher than what is observed in a standard laboratory environment (complete darkness except visual targets), and a recent examination of juveniles at risk of schizophrenia conducted by our group under such laboratory conditions revealed no significant increase of hypometria. We therefore asked whether differences in background structure or target step timing could be responsible for these discrepancies. We argued that there might be particular experimental sets in which the saccadic tracking system is challenged to a degree where it would operate at the limits of its capability in normal subjects and would disclose otherwise unnoticeable impairments in patients.

Ocular lateropulsion is common in lateral medullary infarcts.1,2 It is assumed to be due to damage to fibers that project from the contralateral inferior olivary nucleus via the inferior cerebellar peduncle to the Purkinje cells in the cerebellar cortex.3 Disinhibition of the Purkinje cells leads to decreased activity of the ipsilateral fastigial nucleus in the vermis. The fastigial nucleus projects, via the uncinate fasciculus in the superior cerebellar peduncle, upon the medial and superior vestibular nuclei and the paramedian pontine reticular formation of the contralateral side and accelerates contralateral saccades. Its inhibition results in a motor bias of horizontal eye movements toward the side of the lesion.3,4 The eyes tend to move conjugately to the side of the infarct while there is no limitation in ductions or versions, as opposed to gaze palsy. The ocular drift can be seen as a continuous tendency of the eyes to look ipsilaterally during primary gaze or—in its mild form—can be observed as gaze deviation followed by a corrective movement to the midline when the eyes are opened following lid closure. On saccade testing, the patient performs hypermetric saccades to the side of the stroke and hypometric saccades contralaterally.2 We describe a patient with an old right homonymous hemianopia due to a left temporo-occipital stroke who reported improved vision after a left lateral medullary infarction that caused left ocular lateropulsion. A 49-year-old man was admitted because of sudden onset of vertigo, dysphagia, vertical diplopia, and loss of coordination in the left limbs. His medical history comprised non-insulin-dependent diabetes mellitus. …

Multiple hypometric (undershooting) saccades are generally reported as a compensatory strategy in adults with homonymous hemianopia. However, hypermetric (overshooting) saccades have been reported to develop spontaneously as a beneficial strategy in response to predictable targets. We examined the saccades of 10 children (aged 5 to 16 years) with homonymous hemianopia to determine the type of compensatory eye-movement strategies employed 6 months to 16 years after hemianopia onset. Homonymous hemianopia was identified using perimetry and/or pattern visual evoked potentials and supported with results of neuroimaging. Eye movements were recorded using bitemporal electrooculography. Saccades were elicited to a red light source in a semipredictable paradigm. We found that hypermetria was not a consistent compensatory strategy in our patients. In spite of the predictability of our paradigm and the long follow-up period, multiple hypometric saccades into the blind field appeared to be the preferred strategy.

In this study, the execution of delayed saccades in 15 DSM-III-R-schizophrenic patients and 15 normal subjects was investigated. While looking at a central fixation cross, a peripheral target was randomly presented at 10 degrees eccentricity. Subjects were instructed to saccade to the target when the fixation cross was switched off after 500 ms. Two experiments were conducted: (a) a delayed-saccade task and, (b) a memory-guided saccade task, that is, the peripheral target was switched off together with the fixation cross. In the delayed-saccade task, amplitudes of regular saccades did not differ between schizophrenic patients and normals. In the memory-guided saccade task, schizophrenic subjects showed marked hypometric saccades. Incorrect delayed saccades (while the fixation cross was on) were also hypometric in schizophrenics, but not in normal controls. The final eye position, i.e., the position reached after the execution of correction saccades, however, did not differ between patients and controls. This means that schizophrenics show a deficit in the programming of primary saccades, if the fixation point and the peripheral target are (a) both visually presented or (b) both memorized. The results support the hypothesis that these saccades are the result of an averaging effect between the fixation point and the peripheral target. It is further hypothesized that these deficits might be explained by a lack of prefrontal inhibition of ocular fixation areas.

Background Depression in people aged 65 and more appears to be a major public health problem. Efficient mechanisms of inhibition are important to communicate with other people and to interact with the environment but seem to be deficient in young depressed patients. This function needs to be evaluated in late life depression which has specific features. Method Twenty inpatients (mean age = 70.4) meeting DSM-IV criteria for major depressive disorder were compared to forty seven healthy controls. They performed a neuropsychological and psychiatric assessments and two eye movement tasks: a prosaccades task to obtain basic parameters of eye movements and an antisaccade task to evaluate the inhibition capacities. Results In comparison with healthy subjects, depressed patients showed impaired performances in both oculomotor tasks. Concerning the prosaccade trial, depressed patients had higher reaction times and error rates than healthy controls. In both populations, hypometric saccades are the main kind of error. In the antisaccade task, reaction times and error rates were also higher in depressed patients than healthy subjects. However, the two populations showed similar correction rates. Conclusion The results of this study offer new insight on the inhibition impairment of aged major depressive patients by two simple eye movement tasks. The findings indicate psychomotor retardation and inhibition impairment, consistent with the findings obtained in young depressed subjects.

Recent intensive neurophysiological experiments in the monkey have demonstrated the function of the cerebellum in the control of saccadic eye movements. Microstimulation studies on monkeys have determined that the cerebellar cortex, which is specifically involved in the control of saccades, is located in vermal lobules VIc and VII. The Purkinje-cell axons arising from this vermal area terminate almost exclusively in an ellipsoidal region which protrudes dorsocaudally from the fastigial nucleus. Saccade-related cells in the fastigial nucleus are located exclusively in the ellipsoidal region. Microstimulation of the vermis modulated the activity of saccade-related cells in the fastigial nucleus, and then produced dysmetric saccades. In this study, we investigated effects of cerebellar stimulation on saccade metrics in man using a transcranial magnetic stimulation (TMS) device. Focal TMS was applied over the posterior cerebellum at an area approximately 7 mm lateral and caudal to the inion during horizontal visually guided saccades in six normal subjects. The TMS device was triggered after the onset of saccades with a latency of 0, 20, 40 or 60 ms. We investigated the effect of TMS on the amplitude and velocity of saccadic eye movements. For visually guided saccades directed contralateral to the stimulation side, TMS of the posterior cerebellum with the latency of 0 ms produced hypometric saccades followed by corrective saccades. Transcranial magnetic stimulation with latencies of 20, 40 and 60 ms had no effect on saccade metrics. On the other hand, for ipsilateral saccades, TMS with latencies of 0, 20 and 40 ms produced hypermetric saccades followed by postsaccadic drift.(ABSTRACT TRUNCATED AT 250 WORDS)

Initial saccades to visual targets are generally not precise in either normal subjects or patients with saccadic dysmetria. Quantitative criteria have to be applied to clearly distinguish between normal and pathological saccadic dysmetria, which is often found in patients with cerebellar lesions. To establish these criteria, the accuracy of visually guided horizontal saccades (10 degrees and 20 degrees target steps) was studied in a group of 24 patients with lesions affecting the cerebellum or its connections, and compared with data from 17 normal subjects. Eye movements were recorded with infrared oculography. Saccades of normal subjects had an average gain of 0.92-0.95 depending on the stimulus condition. Centripetal saccades were significantly larger than centrifugal saccades, for 20 degrees target steps. Most patients (n = 15) had significantly larger saccadic amplitudes than normal subjects (hypermetria), at least in one direction. Saccades in the opposite direction could be either hypometric, hypermetric or normal. Two patients had hypometric saccades in both directions. For one of the patients with hypermetria, in addition, the amplitude difference between centrifugal and centripetal saccades was significantly larger than in the normal subjects. Five patients had no significant pathology of the initial (primary) saccade, but a pathological pattern of corrective saccades. Two patients had normal saccades under all conditions. The quantitative comparison with normal subjects allows the detection even of mild pathology. According to our results, a pathology can be assumed when the average gain of saccades in at least one direction is 1.0 or more, or when more than two out of 20 saccades are followed by two corrective saccades of which the last is in the direction opposite to the initial saccade (pathological pattern of corrective saccades). Target steps of 20 degrees reveal a pathological condition more often than 10 degrees target steps. The application of quantitative criteria might be useful to establish a diagnosis of pathologic saccadic dysmetria even in instances in which it is clinically not obvious.

SummaryIn a small (n = 15) clinically heterogeneous group of patients with dementia of the Alzheimer-type or vascular dementia, abnormally high frequency of saccadic intrusions during fixation was significantly correlated to the Mini-Mental-State-Examination (MMSE) scores. In addition, the latency of saccades and hypometric saccades also correlated significantly to MMSE-scores. The results point to the possible use of saccadic eye movement as a physiological marker of cognitive performance.

• Nine patients had a lateral medullary infarction. Examination during the acute phase of the lesion to determine oculomotor and oculovestibular functions showed that all patients had hypermetric saccades and increased gain of the vestibulo-ocular reflex (VOR) to the side of the lesion and hypometric saccades and decreased gain of the VOR to the side opposite the lesion. These abnormalities may be the consequence of the isolation of the vestibular nuclei from the flocculus, with loss of saccadic and vestibular gains by the cerebellum.

The eye movements of four patients with ataxia telangiectasia (AT), three of whom had an unusual neurological presentation, were studied. All had striking abnormalities of saccadic generation with markedly hypometric saccades, increased saccadic latency, but normal saccadic velocity. Three patients used head thrusts to aid refixation. In addition, there was absence of smooth pursuit and optokinetic nystagmus, and hyperactive vestibular responses. Two of the four patients had, in addition, periodic alternating nystagmus. This combination of an ocular motor apraxia with superadded cerebellar ocular motor abnormalities, and possibly periodic alternating nystagmus, should strongly suggest the diagnosis of AT, even if the clinical syndrome is otherwise atypical.

A case of Louis-Bar's syndrome (ataxia telangiectasia) in a 9-year-old girl was presented and * study was made of the nature and origin of oculomotor abnormalities in association with the syndrome. 1. Nature of the oculomotor abnormalities The following abnormalities were observed: 1) hypometric saccades; 2) difficulty of keeping eye position (notably non-central gaze); 3) coarse fixation jerks; 4) downward vertical nystagmus elicited on lateral gaze; 5) weak convergence; 6) suppression of optokinetic nystagmus; 7) disturbance of smooth following eye movements; 8) Roth-Bielschowsky sign; 9) flutter-like oscillations of the eye (Cogan). In addition to these, fixation nystagmus is also reported in the literature. To be noted is that the symptoms 3), 7) and 9) are entirely new additions to the ocular manifestations of this syndrome. 2. Origin Aside from these oculomotor abnormalities, conspicuous cerebellar symptoms were the only neurologic manifestations in the present case. Along with recent demonstration that the pathology of the central nervous system of the syndrome is characterized by diffuse atrophy occurring almost within the confines of the cerebellum or at least by the absence of significant lesions in the brain stem and cerebrum, it was suggested that the oculomotor abnormalities mentioned above are all of cerebellar origin. In this connection, special reference was made to the symptoms 5), 6), 8) and 9).

We quantified the horizontal pursuit and saccadic function of 14 parkinsonian patients and 10 normal subjects matched for age. Eight patients had mild, and 6 advanced disease. Ocular motor deficits were more marked in patients with advanced disease. Saccadic reaction times and postsaccadic refractory periods were prolonged. Peak saccadic velocities were significantly reduced. Slow saccades may be caused by inappropriate coactivation of opposing ocular muscles. Multiple step, hypometric saccades were abnormally frequent. Correct final eye position towards a brief target flash was attained without visual feedback. Brief corrective intervals occurred after hypometric saccades. They are attributed to internal (nonvisual) efference copy feedback of eye position errors. Frequent square wave jerks were also a feature of Parkinson's disease. Smooth pursuit gain was lowered in all patients while tracking sinusoidal targets at frequencies from 0.25 to 1 Hz. Pursuit gain was uniformly reduced at all target velocities at each frequency. This decrease in gain indicates that dysfunction of the gain element, rather than abnormal drop acceleration saturation is responsible for impaired smooth pursuit. The results indicate that Parkinson's disease damages structures involved in the regulation of the saccadic and pursuit systems. We infer that nigrostriatal pathways, known to be damaged in Parkinson's disease, control the latency, velocity and amplitude of saccades, and the gain element of smooth pursuit.