Classification & Examination of Eye Movements
Eye movements are either fast or slow. Fast eye movements include voluntary or involuntary refixation movements (saccades) and the fast phases of vestibular and optokinetic nystagmus (see later in the chapter). The fast eye movement system is tested by command refixation movements and by the fast phase of vestibular and optokinetic nystagmus.
Slow eye movements include pursuit movements, which track a slowly moving target once the saccadic system has placed the target on the fovea and which are tested by asking a patient to follow a slow, smoothly moving target, the slow phase movements generated by vestibular stimuli, the slow phase of optokinetic nystagmus, and vergence movements, which, unlike all the other forms of eye movements, involve dysconjugate movements of the two eyes.
Under physiologic conditions, vestibular stimulation occurs from head movements. The resulting slow eye movements, known as the vestibulo-ocular responses (VOR), compensate for the head motion such that the position of the eyes in space remains static and steady visual fixation can be maintained. The doll's head maneuver is a clinical method of testing the VOR. The patient is asked to fixate on a target while the examiner moves the head in a horizontal or vertical plane. If the VOR is deficient, the compensatory eye movements are insufficient and must be supplemented by saccadic movements to maintain fixation. The head motion must be rapid; otherwise, pursuit mechanisms dominate the ocular motor response. In the unconscious patient, the doll's head maneuver is used to assess brainstem function. Since the pursuit and saccadic systems are not operative, the head movements can be slow. Absence of the VOR leads to failure of the eyes to move within the orbit. Other methods of vestibular stimulation are whole body rotation and caloric testing (see later in the chapter).
Abnormalities of Eye Movements
Owing to the multiplicity of pathways involved in the supranuclear control of eye movements, with origins in different areas of the brain and an anatomic separation in the brainstem of the horizontal and vertical eye movement systems, disorders of the supranuclear pathways characteristically produce a dissociation of effect upon the various types of eye movements. Thus, the clinical clues to a supranuclear lesion are a differential effect on horizontal and vertical eye movements or upon saccadic, pursuit, and vestibular eye movements. In diffuse brainstem disease, such features may not be apparent, and differentiation from disease at the neuromuscular junction or within the extraocular muscles on clinical grounds can be difficult.
Disease of the internuclear pathways results in a disruption of the conjugacy of eye movements. In infranuclear disease, the pattern of eye movement disturbance usually complies with that expected of a lesion involving one or more cranial nerves or their nuclei.
Lesions of the Supranuclear Pathways
A seizure focus in the frontal lobe may cause involuntary turning of the eyes to the opposite side. Destructive lesions cause transient deviation to the same side, and the eyes cannot be turned quickly and voluntarily (saccadic movement) to the opposite side. This is called frontal gaze palsy, and recovery occurs when the opposite frontal eye field substitutes. Ocular pursuit to the opposite side is retained. There is no diplopia.
Smooth ocular pursuit may be lost with posterior lesions of the hemispheres. The patient is unable to follow a slowly moving object in the direction of the gaze palsy. The command (fast) eye movement is not lost, so pursuit is “saccadic.”
Phenytoin can significantly affect saccades. Sedative agents and carbamazepine can alter smooth pursuit eye movements.
Lesions of the posterior commissure of the midbrain cause impairment of conjugate upgaze. Lesions dorsal and medial to the red nuclei produce a downgaze paresis.
Dorsal midbrain syndrome (Parinaud's syndrome) is characterized by loss of voluntary upward gaze, convergence-retraction nystagmus, pupillary light-near dissociation, and eyelid retraction (Collier's sign). There may also be insufficiency or spasm of convergence and/or accommodation, and loss of voluntary downward gaze. Conjugate horizontal ocular movements are usually not affected. The syndrome results from tectal or pretectal lesions affecting the periaqueductal area. Pineal tumors, hydrocephalus, midbrain infarcts or arteriovenous malformations, and trauma may be responsible.
Lesions of the paramedian pontine reticular formation produce an ipsilateral horizontal gaze palsy affecting saccadic and pursuit movements. Vestibular slow-phase movements are preserved owing to the direct pathway from the vestibular nuclei to the abducens and oculomotor nuclei.
Lesions of the brainstem that cause gaze palsies include vascular accidents, arteriovenous malformations, multiple sclerosis, tumors (pontine gliomas, cerebellopontine angle tumors), and encephalitis.
Spasm of the Near Response
Spasm of the near response, also known as convergence or accommodative spasm, is usually caused by functional disease, but it may be caused by a midbrain lesion. It is characterized by convergent strabismus with diplopia, miotic pupils, and spasm of accommodation (induced myopia).
In functional disease, the features are usually intermittent and provoked by eye movement examination. Cyclopentolate 1%, one drop in each eye twice daily, with reading glasses to compensate for loss of accommodation may be helpful. Psychiatric consultation may be indicated.
Convergence insufficiency is characterized by diplopia for near vision in the absence of any impairment of adduction on monocular testing, refractive error, particularly presbyopia, having been excluded. It is caused by functional disease or dysfunction of the supranuclear pathway for convergence in the midbrain. In organic lesions, pupillary miosis still occurs when convergence is attempted, whereas in functional disease, it does not.
The medial longitudinal fasciculus is an important fiber tract extending from the rostral midbrain to the spinal cord. It contains many pathways connecting nuclei within the brainstem, particularly those concerned with extraocular movements. The most common manifestation of damage to the medial longitudinal fasciculus is an internuclear ophthalmoplegia, in which conjugate horizontal eye movements are disrupted owing to failure of coordination between the abducens nerve nucleus in the pons and the oculomotor nerve nucleus in the midbrain. The lesion in the brainstem is ipsilateral to the eye with the adduction failure and contralateral to the direction of horizontal gaze that is abnormal. In the mildest form of internuclear ophthalmoplegia, the clinical abnormality is restricted to a slowing of saccades in the adducting eye, producing transient diplopia on lateral gaze. In the most severe form, there is complete loss of adduction on horizontal gaze, producing constant diplopia on lateral gaze (Figure 14–12). Convergence is characteristically preserved in internuclear ophthalmoplegia except when the lesion is in the midbrain, when the convergence mechanisms may also be affected. Another feature of internuclear ophthalmoplegia is nystagmus in the abducting eye on attempted horizontal gaze, which is at least in part a result of compensation for the failure of adduction in the other eye. In bilateral internuclear ophthalmoplegia, there may also be an upbeating nystagmus on upgaze due to failure of control of gaze holding in the upward direction, and the eyes may be divergent; this is known as the wall-eyed bilateral internuclear ophthalmoplegia (WEBINO) syndrome.
Internuclear ophthalmoplegia may be due to multiple sclerosis (particularly in young adults), brainstem infarction (particularly in older patients), tumors, arteriovenous malformations, Wernicke's encephalopathy, and encephalitis. Bilateral internuclear ophthalmoplegia is most commonly due to multiple sclerosis.
A horizontal gaze palsy combined with an internuclear ophthalmoplegia, due to a lesion of the abducens nucleus or paramedian pontine reticular formation extending into the ipsilateral medial longitudinal fasciculus, affects all horizontal eye movements in the ipsilateral eye and adduction in the contralateral eye. This is known as a “one-and-a-half syndrome,” or paralytic pontine exotropia.
Nuclear & Infranuclear Connections
Ocular Motor Nerve Palsies
Ocular motor nerve palsies result in impairment of eye movements, the pattern being determined by which extraocular muscles are involved, ocular misalignment, which at least in the acute stage also varies in severity with different gaze positions according to which muscles are paretic, and ptosis if there is palsy of the levator palpebrae superioris muscle. Misalignment of the visual axes results in diplopia, unless there is suppression, which more commonly develops in children than adults. Dizziness or disequilibrium may be associated but disappears with monocular patching. Abnormal head posture may develop. In sixth nerve palsy, there is head turn to the side of the palsy, and in fourth nerve palsy, there is head tilt to the opposite side. Paresis of an extraocular muscle can be simulated by restriction of action of the yoke muscle, for example limitation of abduction may be due to medial rectus restriction rather than lateral rectus paresis. Assessment of saccadic velocity may be helpful, but forced duction tests may need to be performed. Saccadic velocity may also help identify which muscle is paretic, for instance in differentiating superior oblique from inferior rectus palsy.
There is wide variation in the site of damage and etiology in ocular motor nerve palsies. Nuclear lesions have specific localizing features. Fascicular lesions within the brainstem resemble peripheral nerve lesions but usually can be differentiated on the basis of other brainstem signs. Any extraocular muscle palsy that occurs with minor head trauma (subconcussive injuries) should be investigated for an intracranial lesion. In ischemic (microvascular) palsies, recovery by 4 months is the rule. Palsies that have not started to recover by then—especially those involving the sixth nerve—should be evaluated for another cause, particularly a structural lesion. Urgent investigation should be undertaken when there is evidence of multiple cranial nerve dysfunction or for any extraocular muscle palsy in a young adult. Assessment of any ocular motor nerve palsy must include assessment of second, fifth, and seventh cranial nerve function.
The motor fibers arise from a group of nuclei in the central gray matter ventral to the cerebral aqueduct at the level of the superior colliculus. The midline central caudal nucleus innervates both levator palpebrae superioris muscles. The paired superior rectus subnuclei innervate the contralateral superior rectus. The efferent fibers decussate immediately and pass through the opposite superior rectus subnucleus. The subnuclei for the medial rectus, inferior rectus, and inferior oblique muscles are also paired structures but innervate the ipsilateral muscles. The fascicle of the oculomotor nerve courses through the red nucleus and the inner side of the substantia nigra to emerge on the medial side of the cerebral peduncles. The nerve runs alongside the sella turcica, in the outer wall of the cavernous sinus, and through the superior orbital fissure to enter the orbit. The superior branch innervates the levator palpebrae and superior rectus muscles and the inferior branch of all other muscles and the sphincter.
The parasympathetics arise from the Edinger–Westphal nucleus just rostral to the motor nucleus of the third nerve and pass via the inferior division of the third nerve to the ciliary ganglion. From there the short ciliary nerves are distributed to the sphincter muscle of the iris and to the ciliary muscle.
Lesions of the third nerve nucleus typically affect the ipsilateral medial and inferior rectus and inferior oblique muscles, both levator muscles, and both superior rectus muscles. There will be bilateral ptosis and bilateral limitation of elevation as well as limitation of adduction and depression ipsilaterally.
From the fascicle of the nerve in the midbrain to its eventual termination in the orbit, third nerve palsy produces purely ipsilateral dysfunction. The exact pattern depends on the extent of the palsy, but in general the ipsilateral eye is turned out by the intact lateral rectus muscle and slightly depressed by the intact superior oblique muscle. The eye may only be moved laterally. (Incyclotorsion from the action of the intact superior oblique muscle can be observed by watching a small blood vessel on the medial conjunctiva as depression of the eye is attempted.) There can be a dilated fixed pupil, absent accommodation, and ptosis of the upper lid, often severe enough to cover the pupil. The pattern of pupil abnormality may be influenced by concomitant Horner's syndrome (sympathetic paresis) resulting in a relatively small unreactive pupil or aberrant regeneration (see later in the chapter).
Ischemia, intracranial aneurysm, head trauma, and intracranial tumors are the most common causes of third nerve palsy in adults. Causes of ischemic (microvascular) palsy include diabetes mellitus, hypertension, hyperlipidemia, and systemic vasculitis. Aneurysm usually arises from the junction of the internal carotid and posterior communicating arteries. Intracranial tumor may cause oculomotor palsy by direct damage to the nerve or due to mass effect. Pupillary dilation, initially unilateral and then bilateral, is an important sign of herniation of the medial temporal lobe through the tentorial hiatus (tentorial herniation) due to a rapidly expanding supratentorial mass. Bilateral peripheral third nerve palsies can be caused by interpeduncular lesions, such as basilar artery aneurysm.
A useful guide clinically is that in ischemic lesions the pupillary responses are spared, whereas in compression, including aneurysmal, the pupil is involved, initially loss of reactivity and then also dilation. Less than 5% of vascular third nerve palsies are associated with complete pupillary palsy, and in only 15% there is partial pupillary palsy. Painful isolated third nerve palsy with pupillary involvement necessitates emergency investigation for ipsilateral posterior communicating artery aneurysm. Such investigation may also be indicated in painful isolated third nerve palsy without pupillary involvement and in young patients with painless isolated third nerve palsy with pupillary involvement.
Monocular elevator paralysis—inability to elevate one eye in both abduction (superior rectus) and adduction (inferior oblique)—can be due to paresis of the superior division of the third nerve (tumor, sinusitis, postviral) but also occurs as a congenital defect or in thyroid ophthalmopathy, orbital myositis, orbital floor fracture, myasthenia gravis, and midbrain stroke.
Third nerve palsies in children may be congenital or may be due to ophthalmoplegic migraine, meningitis, or postviral.
Oculomotor Synkinesis (Aberrant Regeneration of the Third Nerve)
This phenomenon is characterized by inappropriate activation of muscles innervated by the oculomotor nerve, including (1) lid dyskinesias due to inappropriate activation of levator palpebrae superioris either on horizontal gaze (eyelid elevates on attempted adduction) or on vertical gaze (eyelid elevates on attempted depression (“pseudo-Graefe's sign”); (2) adduction or retraction on attempted upgaze due to inappropriate activation of medial rectus or inferior rectus; (3) pupillary constriction on attempted adduction or depression; and (4) a monocular vertical optokinetic nystagmus response (due to coactivation of superior rectus, inferior oblique and inferior rectus muscles fixing the involved eye, allowing only the normal eye to respond to the moving target).
Oculomotor synkinesis most commonly occurs in congenital third nerve palsy or during recovery from acute third nerve palsy due to trauma or aneurysmal compression (secondary oculomotor synkinesis). It may also occur as a primary phenomenon in chronic compression, usually due to an internal carotid aneurysm or meningioma in the cavernous sinus. Oculomotor synkinesis is not a feature of ischemic oculomotor palsy.
Cyclic oculomotor palsy can complicate congenital third nerve palsy; it is a rare, predominantly unilateral event, with a typical third nerve palsy showing cyclic spasms every 10–30 seconds. During these intervals, ptosis improves and accommodation increases. This phenomenon continues unchanged throughout life but decreases with sleep and increases with greater arousal.
Marcus Gunn Phenomenon (Jaw-Winking Syndrome)
This rare usually congenital condition consists of elevation of a ptotic eyelid upon movement of the jaw. Acquired cases occur after damage to the oculomotor nerve with subsequent innervation of the lid (levator palpebrae superioris) by a branch of the fifth cranial nerve.
Motor (entirely crossed) fibers arise from the trochlear nucleus just caudal to the third nerve at the level of the inferior colliculus; they then run posteriorly, decussate in the anterior medullary velum, and wind around the cerebral peduncles. The fourth nerve travels near the third nerve along the wall of the cavernous sinus to the orbit, where it supplies the superior oblique muscle. The fourth nerve is unique among the cranial nerves in arising from the dorsal brainstem.
Congenital trochlear palsy is probably not usually neurogenic in origin but due to developmental anomaly within the orbit. It may present in childhood with an abnormal head posture (see later in the chapter) or in childhood or adult life with eyestrain or diplopia due to reduced ability to overcome the vertical ocular deviation (decompensation). Acquired trochlear palsy is commonly traumatic. The nerve is vulnerable to injury at the site of exit from the dorsal aspect of the brainstem. Both nerves may be damaged by severe trauma as they decussate in the anterior medullary velum, resulting in bilateral superior oblique palsies. Acquired trochlear palsy may also be ischemic (microvascular) or secondary to posterior fossa surgery. Rarely, posterior fossa tumors may present with an isolated trochlear palsy.
Superior oblique palsy results in upward deviation (hypertropia) of the eye, which increases when the patient looks down and to the opposite side. In addition, in acquired palsy, there is excyclotropia; therefore, one of the diplopic images will be tilted with respect to the other. Thus, torsional diplopia indicates an acquired palsy and lack of torsional symptoms indicates a congenital palsy. Tilting the head toward the involved side increases the vertical ocular deviation (Bielschowsky head tilt test). Tilting the head away from the side of the involved eye may relieve the diplopia, and patients frequently adopt such a head tilt. History of an abnormal head posture during childhood, which may be confirmed by review of family photographs and a large vertical prism fusion range, are strong clues that a trochlear palsy is congenital. In bilateral traumatic palsy, there is usually a chin-down head posture. Strabismus surgery is effective in decompensated congenital palsy not controlled by prisms and for unresolved acquired palsy.
Superior Oblique Myokymia
Contrary to its name, this is an uncommon acquired tremor of the superior oblique muscle, affecting only one eye. The patient complains of episodes of torsional and/or vertical oscillopsia or double vision, which may be precipitated by looking down, such as when reading. Various anticonvulsants, typically carbamazepine, or β-blocker eye drops can be beneficial. Superior oblique muscle surgery may be undertaken. The cause may be compression of the trochlear nerve by an aberrant artery, for which intracranial surgery may be successful.
Motor (entirely uncrossed) fibers arise from the nucleus in the floor of the fourth ventricle in the lower portion of the pons near the internal genu of the facial nerve. Piercing the pons, the fibers emerge anteriorly, the nerve running a long course over the tip of the petrous portion of the temporal bone into the cavernous sinus. It enters the orbit with the third and fourth nerves to supply the lateral rectus muscle.
The abducens nucleus contains the motor neurons to the ipsilateral lateral rectus and the cell bodies of interneurons innervating the motor neurons to the contralateral medial rectus. It is the final common relay point for all horizontal conjugate eye movements, and a lesion within the nucleus will produce an ipsilateral horizontal gaze palsy affecting all types of eye movement, including vestibular movements. This contrasts with a lesion of the paramedian pontine reticular formation, in which vestibular movements are preserved.
Abducens Nerve Palsy (See Also Chapter 12)
This is the most common single extraocular muscle palsy. Abduction of the eye is reduced or absent; esotropia is present in the primary position and increases with distance fixation and upon gaze to the affected side. Ischemia (arteriosclerosis, diabetes, migraine, and hypertension) is a common cause. However, increased intracranial pressure, in which the abducens palsy is a false localizing sign, intracranial tumors, particularly at the base of the skull, trauma, meningitis, demyelination, dural arteriovenous fistula, and intracranial hypotension including after lumbar puncture are other causes. Infections can produce sixth nerve palsy from direct involvement, as in middle ear infection, ischemia, or meningitis. Arnold–Chiari malformation (congenital downward displacement of the cerebellar tonsils) can produce sixth nerve palsy due to traction but can also produce a distance esotropia without limitation of abduction due to cerebellar dysfunction. A child with a sixth nerve palsy should be evaluated for a brainstem tumor (glioma) or inflammation if trauma was not present or if trauma was minimal. Möbius' syndrome (congenital facial diplegia) can be associated with a sixth nerve or conjugate gaze palsy. Pseudo-sixth nerve palsies can occur in Duane's syndrome, spasm of the near response, thyroid eye disease, myasthenia, or long-standing strabismus and in medial rectus entrapment by an ethmoid fracture.
Duane's syndrome is uncommon (<1% of cases of strabismus) and in almost all cases congenital. It is a stationary, nearly always unilateral condition characterized by complete or partial deficiency of abduction, with retraction of the globe and narrowing of the lid fissure on adduction. Congenital absence of the sixth nerve with coinnervation of the lateral rectus by a branch of the third nerve is the likely cause in most cases and other congenital anomalies are common. The visual handicap is seldom severe. Visual acuity is usually normal. Unless there is a marked abnormal head posture, strabismus surgery is best avoided.
Gradenigo's syndrome is characterized by pain in the face (from irritation of the trigeminal nerve) and abducens palsy. The syndrome is produced by disease of the tip of the petrous bone and most often occurs as a rare complication of otitis media with mastoiditis or petrous bone tumors.
Syndromes Affecting Cranial Nerves III, IV, & VI
Superior Orbital Fissure Syndrome
All the ocular motor nerves pass through the superior orbital fissure and can be affected by tumor, inflammation, or trauma involving the fissure.
This syndrome is similar to the superior orbital fissure syndrome with the addition of optic nerve signs and usually greater proptosis. It is also caused by tumor, inflammation, or trauma.
Sudden Complete Ophthalmoplegia
Complete ophthalmoplegia of sudden onset can be due to extensive brainstem vascular disease, Wernicke's encephalopathy, Fisher's syndrome, bulbar poliomyelitis, pituitary apoplexy, basilar aneurysm, meningitis, diphtheria, botulism, or myasthenic crisis.
The cerebellum has an important modulating influence on the function of the neural integrators. Thus, it is involved in gaze holding and the control of saccades, particularly the relationship between the pulse and the step of saccade generation. Cerebellar dysfunction produces gaze-evoked nystagmus, by its influence on gaze holding, and abnormalities of saccades, including saccadic dysmetria in which the saccadic amplitude is inaccurate, and postsaccadic drift due to a mismatch between the pulse and step of the saccade.
The cerebellum is also important in the control of pursuit eye movements, and cerebellar dysfunction may thus result in broken (saccadic) pursuit. It may also result in ocular misalignment, vertical due to skew deviation or horizontal.