Binocular saccadic eye movements in multiple sclerosis
Introduction
The diagnosis of multiple sclerosis (MS) is based on clinical criteria. In addition to neurological examination and magnetic resonance imaging (MRI), a wide range of paraclinical tests support the diagnosis, which rests predominantly on objective evidence concerning two separate lesions in the central nervous system (Poser et al., 1983). In case two clinically distinct lesions do not occur at the same time, detection of a second (possibly subclinical) lesion is of paramount importance in order to obtain a definite diagnosis. Because a rather large part of the central nervous system is involved in visual-oculomotor activity, a randomly located MS lesion will frequently cause (transient) visual or oculomotor disturbances. Therefore, a study of eye movements may assist in demonstrating neurological dysfunction attributable to lesions that are clinically silent as such. The literature shows that many MS patients develop some form of oculomotor dysfunction at some stage of the disease (Baloh et al., 1978; Mastaglia et al., 1979; Tackmann et al., 1980; Reulen et al., 1983; Müri and Meienberg, 1985; Meienberg et al., 1986; for review see Leigh and Zee, 1991).
The stereotyped nature of saccadic eye movements favors their reproducibility; therefore, measurement of saccadic parameters has been found to be preferable to the recording of smooth pursuit, which varies more as a function of effort and attention (Mastaglia et al., 1982; Meienberg et al., 1986). Several saccadic parameters can be traced to different brain structures. Latency between a change in the stimulus and the saccadic response reflects, among other things, the neural transmission time in both the visual and oculomotor system. Prolonged latencies have been shown to occur in a large percentage of MS patients (Reulen et al., 1983), but the possibility to assess this parameter reliably in routine testing has been discounted (Meienberg et al., 1986). Saccadic inaccuracy, especially hypermetria, is recognized as characteristic of cerebellar dysfunction (Meienberg et al., 1986). However, the most direct evidence of normal or abnormal generation of saccades at the brain stem level is provided by the internal, dynamic properties of the saccades. Normally, a tight relation, called the `main sequence', exists between the peak velocity and duration of saccades and their amplitude (see, e.g. Collewijn et al., 1988). Disturbances of these relations, such as a reduction of peak velocities, have often been found in multiple sclerosis. Very often, such disturbances have the form of an internuclear ophthalmoplegia (INO). This syndrome is characterized by a slowing of adduction, caused by an ipsilateral lesion in the medial longitudinal fasciculus. On attempted lateral gaze, the involved eye is unable to adduct properly; meanwhile the contralateral, abducting eye exhibits a dissociated nystagmus (Baloh et al., 1978).
Mild cases of internuclear ophthalmoplegia, that were clinically indistinct, were frequently evident in electro-oculography obtained from patients with definite multiple sclerosis (Mastaglia et al., 1979; Reulen et al., 1983). More accurate eye movement registration techniques, like infrared reflection oculography, confirmed these results. Meienberg et al. (1986)studied the incidence of internuclear ophthalmoplegia in a large group of patients with multiple sclerosis. In approximately one-third of the cases, an internuclear ophthalmoplegia could be detected by recording the eye movements; only about half of these cases were recognized by clinical examination. Recently, Ventre et al. (1991), using electro-oculography, were able to further improve the detection of subtle forms of INO by introducing a `versional disconjugacy index', i.e. the inter-ocular ratio of abduction and adduction peak velocity. Despite the questionable absolute values that could be obtained with electro-oculography, this ratio appeared to be quite robustly elevated in a group of patients with (probable) multiple sclerosis, compared to an age-matched control group. For diagnostic purposes, this index proved a more useful parameter than the mere analysis of saccadic peak velocity in each eye separately. Ventre et al. (1991)proposed that such binocular saccadic indices might be used as a grading system to quantify the extent of an internuclear ophthalmoplegia. The strength of this approach is that it relies on an internal comparison between the eyes, and thereby circumvents intra- and inter-individual variability in saccadic profiles. Previously, Meienberg et al. (1986)noticed the value of assessing interocular differences instead of absolute peak velocities because, normally, differences between individuals are larger than differences between the two eyes of one individual. The potential of this approach has been further supported by recent work by Bains et al. (1992), who showed that even on a trial-to-trial basis within single normal individuals, variability in profile between saccades made simultaneously by the two eyes is much smaller than variability between successive saccades.
In recent years, the introduction of high resolution imaging techniques such as MRI has detracted from the impact of oculomotor functional assessment on the diagnosis of MS. MRI is, however, not outstanding in visualizing the (sub)structures of the brainstem (Tedeschi et al., 1989). Therefore, `brainstem specific' saccadic parameters, such as `main sequence' data, may still be regarded as a potentially sensitive diagnostic tool for detecting subtle brainstem dysfunction. Notwithstanding the relative practical advantages of electro-oculography, this must be considered an inferior technique in situations in which precise recording of the ocular movements is required. Apart from the general problems with inaccuracy, noise and drift, it distorts the subtle abduction-adduction asymmetry that exists even in normal subjects (Meienberg et al., 1986; Collewijn et al., 1988). Moreover, it does not allow a reliable recording of vertical (saccadic) eye movements. Consequently, there is an absolute shortage of data on vertical eye movements, and the value of the analysis of vertical saccadic eye movements in the diagnosis of multiple sclerosis is unknown.
The present study evaluates binocular saccadic parameters in MS patients, using a highly precise and accurate scleral induction coil method to measure the eye movements (Robinson, 1963; Collewijn et al., 1975). Our attention was mainly focused on the functional integrity of the medial longitudinal fasciculus, and in the light of the developments in the literature described above we emphasized interocular comparison of saccadic parameters on a saccade to saccade basis. The excellent signal-to-noise ratio of our recordings enabled us to study not only the first derivative of eye position, velocity, but also the second derivative, eye acceleration, which is an even more direct index of the development of muscular force than eye velocity. Our aim was to facilitate the detection of INO-pathology, in particular at an early stage at which an INO might escape detection in a clinical examination. We found that the ratio between the peak accelerations of the abducting and abducting eye during horizontal saccades proved to be a very sensitive parameter in detecting INOs that were not diagnosed in routine clinical examination. A brief, preliminary communication of some of our results has appeared (Flipse et al., 1996).
Section snippets
Subjects
Out of 35 patients selected for this study, 26 were successfully recorded. The results of the remaining nine patients could not be used due to technical shortcomings (such as breakage of a coil during the session). The 26 successfully recorded patients were classified into clinically definite (n=21) or probable (n=5) multiple sclerosis according to the criteria of Poser et al. (1983). Their ages ranged from 20 to 67 years (mean 42 years). Clinical examination of eye movements for
Control group
Position, velocity and acceleration profiles of a typical, rightward saccade between targets that were 20° apart, made by a control subject, are shown in Fig. 1. This figure illustrates the characteristic abduction-adduction asymmetries of normal, horizontal saccades. Amplitude, peak velocity and peak acceleration were all slightly larger in the abducting eye than in the adducting eye; concomitantly, saccadic durations were slightly shorter for the abducting eye. For example, for gaze-shifts
Discussion
In the generation of conjugate horizontal saccades, activity of the burst neurons in the paramedian pontine reticular formation is relayed directly to the motoneurons in the abducens nucleus and the lateral rectus muscle of the abducting eye; the motoneurons of the medial rectus muscle of the contralateral, adducting eye are activated through internuclear neurons in the abducens nucleus, the axons of which cross and then ascend in the contralateral MLF to the contralateral oculomotor nucleus (
References (21)
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2022, Journal of the Neurological SciencesCitation Excerpt :This finding is then to be supported by absent OKN quick phases in the diagnostic criteria. One area that has been studied with regard to clinical detection of abnormal saccadic velocities relates to the presence of adduction lag (i.e., pathological slowing of adducting saccades relative to abducting saccades) in internuclear ophthalmoplegia (INO) [51,59–63]. A study investigating the accuracy of clinician detection of INO, as compared to quantitative eye tracking data, revealed that severe INOs fully manifested by impaired adduction range and abducting nystagmus in the contralateral eye were incorrectly identified only 6% of the time by clinicians [9].
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2019, Journal of the Neurological SciencesCitation Excerpt :Furthermore, the versional dysconjugacy index (VDI) of the AUC and Pv/Am were determined. The VDI is the ratio of the abducting eye value to the adducting eye value and is used for quantifying an INO [15,26,27]. As INO is direction dependent, the mean VDI of leftward saccades and the mean VDI of rightward saccades were investigated separately.
A model-based study of internuclear ophthalmoparesis and ocular-motor fatigue in multiple sclerosis
2019, Progress in Brain ResearchCitation Excerpt :However, our results emphasize that a component of horizontal disconjugacy in INO is due to a delayed delivery of the saccadic pulse to the affected eye. While controls show physiological delay in saccade onset between the two eyes of < 2 ms, with saccade onset calculated based on a 40°/s velocity threshold, our results show that this pulse time delay (PTDo) in INO patients is significantly higher, with average values of 10 ms. Also, while other studies have considered the interocular time difference in occurrence of saccadic peak acceleration not a sensitive way to distinguish between INO and healthy controls (Flipse et al., 1997), our results show that PTD calculated as such difference (PTDa) is at least two times greater (average 5–6 ms) than in controls (< 2 ms). Adding measures of PTD to INO modeling may provide an adjunctive study outcome when testing for therapies that improve axonal transmission along the MLF tracts.
Eye Movement Abnormalities in Multiple Sclerosis
2010, Neurologic ClinicsCitation Excerpt :Various metrics from eye movement recordings have been used to quantify INO. These include the versional dysconjugacy index (VDI), which compares the peak velocities for abduction in one eye to adduction in the other.20,21 This measure has the benefit of cancelling intra- and interindividual variations of absolute saccade velocities (caused by fatigue, for example).
Vestibular testing and multiple sclerosis
2010, Handbook of Clinical NeurophysiologyCitation Excerpt :Mild forms of INO can be overlooked on clinical examination and may only be evident with formal oculographic recording. ( Solingen et al., 1977; Muri and Meinberg, 1985; Cipparrone et al., 1989; Flipse, 1997; Frohman et al., 2002; Versino et al., 2002; T. C. Frohman et al., 2003). In one large cohort of patients with multiple sclerosis the accuracy of clinical detection (by 279 physician observers) of INO was compared with that of quantitative infrared oculography.
Quantitative ocular-motor tests analysis in Multiple Sclerosis
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