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|NI FEATURE: THE QUEST - COMMENTARY
|Year : 2016 | Volume
| Issue : 1 | Page : 121-128
Gaze disorders: A clinical approach
Pulikottil Wilson Vinny, Vivek Lal
Department of Neurology, Postgraduate Institute of Medical Education and Research, Chandigarh, Punjab and Haryana, India
|Date of Web Publication||11-Jan-2016|
Department of Neurology, Postgraduate Institute of Medical Education and Research, Chandigarh, Punjab and Haryana
Source of Support: None, Conflict of Interest: None
A single clear binocular vision is made possible by the nature through the oculomotor system along with inputs from the cortical areas as well their descending pathways to the brainstem. Six systems of supranuclear control mechanisms play a crucial role in this regard. These are the saccadic system, the smooth pursuit system, the vestibular system, the optokinetic system, the fixation system, and the vergence system. In gaze disorders, lesions at different levels of the brain spare some of the eye movement systems while affecting others. The resulting pattern of eye movements helps clinicians to localize lesions accurately in the central nervous system. Common lesions causing gaze palsies include cerebral infarcts, demyelinating lesions, multiple sclerosis, tumors, Wernicke's encephalopathy, metabolic disorders, and neurodegenerative disorders such as progressive supranuclear palsy. Evaluation of the different gaze disorders is a bane of most budding neurologists and neurosurgeons. However, a simple and systematic clinical approach to this problem can make their early diagnosis rather easy.
Keywords: Approach to gaze palsy; fixation; gaze; gaze palsy; internuclear ophthalmoplegia; saccade; smooth pursuit; vergence
|How to cite this article:|
Vinny PW, Lal V. Gaze disorders: A clinical approach. Neurol India 2016;64:121-8
| » Introduction|| |
Our world, as we see it, would be meaningless unless the object of interest is always correctly focused on the fovea, the area of central vision. Otherwise, the visual world would appear fuzzy similar to a photograph taken with a slow shutter speed while the camera is moving. This single clear binocular vision is made possible by nature through the oculomotor system via inputs from the cortical areas and their descending pathways to the brainstem. To achieve this goal, six systems of eye movements are brought into play. These are the saccadic system, the smooth pursuit system, the vestibular system, the optokinetic system, the fixation system, and the vergence system. Distinct anatomical substrates from the cortex to the brainstem, converging upon a final common pathway, define these movement systems. Sudden jerky eye movements (saccades) acquire a target by focusing it on the fovea. When the target is in motion, the smooth pursuit and vergence systems are brought into action. Smooth pursuit tracks the moving object horizontally or vertically while the vergence system tracks it in the anteroposterior axis. When the head is in motion, the vestibular system and the optokinetic systems play a help in keeping the target centered on the fovea. All these systems act via a supranuclear control which eventually projects to the final common pathway in the brainstem.
| » Final Common Pathway|| |
The same set of motor neurons and extraocular muscles are brought into action for all kinds of eye movements. This is often referred to as the final common pathway. The brainstem converts what begins as a retinal visual signal, proprioceptive impulse, volitional, and vestibular information into commands for vertical and horizontal eye movements by coding the information into signals for oculomotor nerves (cranial nerves III, IV, and VI). The final destination for the horizontal gaze circuits lies in parapontine reticular formation (PPRF) in the brainstem, which further projects to the abducens nuclear complex comprising the abducens nucleus and interneurons namely the medial longitudinal fasciculus (MLF) [Figure 1]. MLF interconnects the ipsilateral abducens nucleus with the contralateral medial rectus nucleus. Similarly, cells in the rostral interstitial MLF (riMLF) project to the oculomotor nuclei (obliques, superior, and inferior recti) to produce conjugate vertical movements.
|Figure 1: Schematic diagram depicting internuclear connections between the abducens and third nerve nuclei. PPRF - Para pontine reticular formation, VI - Abducens nucleus, MLF - Medial longitudinal fasciculus, IIIrd - Third nerve nucleus|
Click here to view
| » The Saccadic System|| |
The saccadic system exists to acquire a target of interest while exploring our visual world. The word saccade comes from the French word 'saquer'which refers to flicking the reins of a horse. Saccades are rapid, brief conjugate eye movements that are characterized by their ballistic nature and high velocity (400–800°/s). These redirect our line of gaze while trying to acquire a new object of interest, for example, when visually scanning a family photograph. Saccades have traditionally been classified on the basis of the behavioral context in which they are generated. Thus, a reflexive saccade is executed when a novel stimulus attracts enough attention for it to be clearly focussed on fovea, like a new patient with chorea entering the consultation room.
Similarly, voluntary saccades are executed following an internal decision to look in a particular direction like glancing at the clock on the wall after a long tiring day at work.
Voluntary saccades are further divided into memory-guided, predictive, endogenous saccades, and antisaccades.
The metrics used to characterize saccades are the latency, gain, peak velocity, and the final eye position. Latency refers to the length of time between the onset of target to the onset of saccade. Gain is the ratio of the initial saccade amplitude to the final target saccade amplitude. Peak velocity and final eye position are self-explanatory.
Several electrophysiological and inactivation studies have attempted to define various cortical centers for the aforementioned saccades. Based on these studies, the interparietal sulcus corresponds to the generation of reflexive saccades while the frontal eye fields (FEFs) control the voluntary saccades. Supplementary eye fields appear to be involved in generating voluntary saccades particularly in the face of conflicting motor programs. Similarly, the dorsolateral prefrontal cortex is involved in inhibiting inappropriate reflexive saccades and in generating the predictive saccades., Both frontal and parietal areas project to the superior colliculus directly. The frontal areas also project indirectly via the basal ganglia to the superior colliculus. Both the FEF and superior colliculus project to the contralateral PPRF and riMLF. Each FEF and superior colliculus generates contralateral saccades while vertical saccades require simultaneous activity in both FEF or superior colliculi [Figure 2].
|Figure 2: Schematic diagram depicting saccadic pathway. PC - Parietal cortex, FEF - Frontal eye field, DLPFC - Dorsolateral prefrontal cortex, SEF - Supplementary eye field|
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| » The Step, Pulse, and Neural Integrators|| |
To produce effective conjugate saccadic movements, the mechanical resistance of the orbit which is elastic by nature, must be overcome. The brainstem translates multiple cortical inputs into signals for the oculomotor nerves. These input signals are coded for velocity and position. The neural integrators achieve this by means of the pulse and step mechanism. The velocity command is the pulse while position command is the step. The pulse can also be considered to be the phasic component giving the torque needed to overcome the viscous drag of the orbital tissues, with the step being the tonic component giving the torque needed to overcome the elastic recoil forces. The velocity command (pulse) is executed by the burst cells and the position command (step) by the omnipause and the tonic neurons [Table 1]. The neural integrator helps in the smooth coordination between the velocity and the position commands [Figure 3].
| » The Pursuit System|| |
Unlike the saccadic system, the smooth pursuit system kicks into action while tracking an object of interest that is in motion. An apt example would be a spinner watching his delivery being hit for a six by the batsman or a bird flying across the sky. The smooth pursuit system cannot follow objects moving faster than 30–40°/s. Faster moving objects elicit saccades.
The smooth pursuit system is driven by the visual motion sensed by the striate cortex through pathways that connect the cortical centers in the temporal and the frontal lobe with pursuit-related areas in the brainstem and the cerebellum. In an animal experiment with monkeys, the perceived motion was first processed in the middle temporal (MT) and medial superior temporal (MST) areas in the superior temporal sulcus. Oculomotor signals for pursuit are generated here which then project to the dorsolateral pontine nuclei in the brainstem from where the fibers decussate to the vestibulocerebellum. Signal then passes to the vestibular nuclei and then decussates again to reach the final common pathway of the oculomotor nuclei. The smooth pursuit pathway, therefore, decussates twice generating pursuits to the ipsilateral side of its cortical origin [Figure 4]. The cerebellar flocculus maintains pursuit during steady state tracking while vermis plays a role when target velocity is changing. Areas MT, MST, and posterior parietal cortex have fibers reaching the FEFs. Vertical pursuits follow a similar pathway until the vestibular nuclei, from where the fibers project to the riMLF. Upward pursuit pathways decussate in the posterior commissure before projecting to the final common pathway. A lesion in the posterior commissure thus cause upward gaze palsy. Fibers for the downward gaze pass ventral to the cerebral aqueduct and are thus spared in posterior commissural lesions.,
|Figure 4: Schematic diagram depicting the smooth pursuit pathway. MT - Middle temporal area, MST - Medial superior temporal area, FEF - Frontal eye fields, DLPN - Dorsolateral pontine nuclei, VN - Vestibular nucleus|
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| » The Vestibular System|| |
The vestibular system is summoned to fixate objects of interest on fovea during brief head motions. This is achieved by compensatory eye movements of similar velocity to the head motion but in an opposite direction. This eye movement termed the vestibulo-ocular reflex (VOR) is produced by the labyrinth, vestibular nuclei, and flocculonodular lobe of the cerebellum.
| » The Optokinetic System|| |
The optokinetic system takes over from the vestibular system when the head movements are of large amplitude and too rapid in nature. The pathways are similar to that of the smooth pursuit system.
| » The Vergence System|| |
The vergence system kicks into play during the depth tracking of an object like a batsman watching a delivered ball fast approaching toward him. This system has its origins in the parietal, occipital, and frontal regions.
| » The Fixation System|| |
The fixation system is utilized in looking at a stationary object. Fixation system originates in the occipital lobe.
| » Clinical Evaluation of Gaze Disorders|| |
Abnormalities of eye movement can result from the following:
- Disease of one of the six muscles that move the eye
- Disease of the neuromuscular junction
- A lesion of the cranial nerves (nucleus or nerve fibers) that supply the extraocular muscles
- Anything affecting the mechanical properties of the eyeballs themselves (e.g., a soft tissue mass in the orbit restricting the movement of the eyeball)
- (All of the above are referred to as “nuclear” or “infranuclear palsy.”)
- A dysfunction of the highly specialized neural mechanisms encompassing the saccadic system, smooth pursuit system, vestibular system, optokinetic system, fixation system, and the vergence system that enable the eyes to move together to achieve binocular vision is referred to as “gaze palsy” or “supranuclear palsy.”
As a simple clinical memory aid, it helps to remember that horizontal eye movements are controlled in pons while vertical and torsional eye movements are controlled in the midbrain, with descending modulations from supranuclear structures. Common lesions causing gaze palsies include cerebral infarcts, demyelinating lesions, multiple sclerosis, tumors, Wernicke's encephalopathy, metabolic disorders, and neurodegenerative disorders such as progressive supranuclear palsy (PSP). Patients may present with blurred vision, decreased visual acuity, or oscillopsia. While examining a patient with gaze palsy, some of the parameters that need particular attention are fixation abnormalities, range of movement, saccades and smooth pursuit, ocular alignment, eccentric gaze holding, VOR, optokinetic nystagmus (OKN), and vergence.
| » Fixation|| |
The patient is asked to look straight ahead. Small amplitude saccadic jerks with intersaccadic interval, termed square wave jerks can be appreciated in patients of PSP. This causes the eyes to oscillate about the primary position. Ocular flutter and opsoclonus are eye jerks that occur without intersaccadic interval. While ocular flutter occurs in the horizontal direction, opsoclonus is characterized by its chaotic nature spanning all directions. They occur in brain stem encephalitis, posterior fossa tumors, and paraneoplastic syndromes.
| » Range of Movement|| |
In gaze disorders, lesions at different levels of the brain, spare some of the eye movement systems while affecting the others. The resulting pattern of eye movements helps to localize the lesions. Most unilateral horizontal gaze palsies are produced by lesions in the contralateral frontal or ipsilateral pontine lesions. During bedside examination, pontine lesions can usually be differentiated from the supranuclear lesion by the oculocephalic (doll's eyes) maneuver or the caloric tests and associated neurological signs. Oculocephalic reflexes will be able to overcome the gaze deviations induced by supranuclear lesion by means of preserved VOR while a gaze deviation due to a pontine lesion involving the abducens nuclei will not be overcome by the oculocephalic maneuvers or the caloric tests. Magnetic resonance imaging of the brain will help to further confirm the localization of the lesion. Seizures and myasthenia gravis should be kept in the differential diagnosis when neuroimaging is unrevealing, or when gaze deviations are intermittent, patient is obtunded or has clinical seizures [Figure 5]. In vertical gaze disorders, lack of neuroimaging findings must prompt a diagnostic workup for alternative etiologies including vitamin B12 deficiency, Whipple's disease, drug intoxication, neurosyphilis, and shunt malfunction [Figure 6]. Internuclear ophthalmoplegia (INO) is caused by a lesion in the MLF and is often characterized by adduction weakness on the side of MLF lesion associated with nystagmus of the abducting eye (contralateral eye). Convergence is usually preserved unless the lesion is high up in the midbrain. INO is evident during horizontal saccadic eye movements and while testing for OKN by the optokinetic drum or tape. When the abducens complex is also affected in addition to the MLF, one and a half syndrome results where the only movement spared is abduction in the contralateral eye [Table 2].
| » Saccades|| |
Saccadic eye movements are tested at the bedside by asking the patient to fixate alternately upon two targets 30–40° apart presented 40 cm in front of the midpoint between two eyes. An example would be the examiner's finger and the examiner's nose. Alternatively, the quick phases induced by the optokinetic drum or tape also assess the saccadic eye movements. While observing the saccades, the parameters studied are latency (time to onset of saccades), velocity (slow or fast), accuracy (overshoot or undershoot), square wave jerks, and antisaccades.
Abnormalities in saccades include square wave jerks, macrosquare wave jerks, ocular flutter, opsoclonus, impaired initiation of saccades, dysmetric saccades, and abnormal saccadic velocity.
Hypometric saccades (reaching short of the target) that are also slow in all directions are seen in neurodegenerative disorders. Isolated slowing of the saccades in the horizontal direction results from PPRF lesions in the pons. Ischemia, hemorrhage, pontine glioma, and Gaucher's disease are important etiological possibilities. Isolated slowing of the saccades in the vertical direction results from a midbrain riMLF lesion. Ischemia, PSP, and Niemann–Pick disease are possible etiologies [Table 3] and [Table 4].
|Table 4: Saccadic abnormalities associated with various lesions in neuraxis|
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| » Smooth Pursuit|| |
Bedside examination of the smooth pursuit system involves instructing the patient to track a pencil tip held at 1 m distance and moved with a uniform speed while keeping the head stationary. The patient should be able to fixate on the target. The examiner observes the amplitude, velocity, direction, and smoothness of the pursuit movements. Corrective saccades should be sought for indicating an inappropriate smooth pursuit gain. Smooth pursuit movements that are markedly asymmetric suggest a structural lesion [Table 5].
| » Convergence Movements|| |
Convergence or depth tracking movements can be tested by asking the patient to fixate his vision on a pencil held at 1 m and slowly moving the pencil toward the patient's nose. The point of maximum convergence is where one or both eyes lose fixation and deviate outward. This distance is usually 8–10 cm and usually increases with age.
Midbrain lesions produce convergence defects whereas pontine lesions produce divergence defects. Convergence paralysis can result from Parkinson's disease, PSP, midbrain tumors, hemorrhage, or infarctions among other rarer causes. The weakness of divergence is a manifestation of the lower pontine lesion after lumbar puncture, encephalitis, demyelinating disease, neurosyphilis, posterior fossa tumors, as an initial sign of Miller Fisher syndrome and with Machado–Joseph disease.
| » Optokinetic Nystagmus|| |
This system is tested clinically by means of a drifting visual stimuli across the patient's visual field. This is commonly achieved at the bedside by means of an optokinetic drum or a tape. Alternatively, one may use mobile applications available for this purpose both on the Android and iOS platforms. The optokinetic reflex is composed of two stages. In the first stage, the eye begins to move toward the moving scene rapidly attaining a fast velocity of movement through the smooth pursuit system. The second stage is that of an optokinetic after-nystagmus where the eye jerks back to acquire a new moving target. The examiner should watch for direction and symmetry of the response [Table 6].
| » Vestibular System|| |
The VOR is a type of conjugate eye movement which moves the eye equal and opposite to the head movement. The VOR is classified into vertical, horizontal, and torsional. Head impulse test is used to test the VOR. To test, patient's head is held between both hands, asking him to fixate on a target in front of his eyes followed by very rapidly turning the patient's head horizontally approximately 20–30°. Rapid conjugate eye movements opposite in direction to the head movements are noticed in healthy subjects. This ensures that the eyes remain in the same position irrespective of the head movements thus enabling the target to be always centered on the fovea. In labyrinthine dysfunction, refixation saccades are employed to re-acquire the target, suggesting a VOR deficit. Video-based head impulse testing allows for more accurate quantification of the VOR deficit.
The cancellation or suppression of VOR is a phenomenon which inactivates the VOR when the target is moving in the same direction of the head motion. Suppression of VOR is employed when an individual has to track a target in motion while the head is also moving in the same direction. An intact VOR is a prerequisite to test for cancellation of VOR. This can be tested by asking the patient sitting on a wheelchair to fixate on the extended thumbs of the outstretched arms with palms together in front of him. As the wheelchair is rotated by an assistant, the examiner looks for any refixation saccades. Such corrective refixation saccades during this test are indicative of impaired suppression of the VOR. This deficit usually occurs along with the smooth pursuit abnormalities and generally localizes the lesions to the cerebellum or cerebellar pathways. Alcohol, anticonvulsants, and sedatives can also impair suppression of the VOR by their effects on the cerebellum. If the VOR itself is not intact, for example, in cases of vestibular dysfunction, testing for VOR suppression is best avoided as it may spuriously appear normal.
| » Conclusion|| |
The prospect of evaluation of different gaze disorders often bring uneasiness to most budding neurologists and neurosurgeons. A sound understanding of the anatomical pathways and physiology behind various aspects of gaze is absolutely essential in deciphering the complex maze that constitutes gaze. A proper clinical examination of the various aspects of gaze will help in narrowing the anatomical localization of the culprit lesion. Since many treatable conditions can present with gaze disorders, it is particularly important to look for them to make an early diagnosis and institute timely treatment.
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Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]
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