Ocular gaze disorders

INTRODUCTION — Abnormalities in eye movements can be caused by palsy of isolated ocular muscles, palsy of conjugate movements (gaze), or both [1].

Gaze disorders are reviewed in this topic. Palsies of isolated extraocular muscles are discussed separately:

●(See "Third cranial nerve (oculomotor nerve) palsy in adults".)

●(See "Third cranial nerve (oculomotor nerve) palsy in children".)

●(See "Fourth cranial nerve (trochlear nerve) palsy".)

●(See "Sixth cranial nerve (abducens nerve) palsy".)

TERMINOLOGY — The control of eye movement has three components:

●The supranuclear pathway (from the cortex and other control centers in the brain to the ocular motor nuclei in the brainstem)

●The ocular motor nuclei

●The infranuclear pathway from the ocular motor nuclei to the peripheral nerve, neuromuscular junction, and extraocular muscles (table 1)

Supranuclear structures coordinate the action of extraocular muscles and muscle groups and control two types of eye movements: conjugate version movements, in which both eyes move in the same direction, and vergence movements, in which both eyes move in opposite directions, turning either in (convergence) or out (divergence).

●Gaze palsy – A gaze palsy is an eye movement abnormality in which the two eyes move together but have limited movement in one direction. Gaze palsies are caused by malfunction of one of the "gaze centers" (cortical and brainstem regions responsible for conjugate gaze) or by interruption of the pathways leading from them.

●Nuclear gaze palsy – A gaze palsy that is caused by a lesion in the brainstem gaze center is called a nuclear gaze palsy

●Supranuclear gaze palsy – A gaze palsy caused by a lesion in the cortical gaze center is called a supranuclear gaze palsy.

The patient with supranuclear palsy is unable to move both eyes past the midline in one direction, and the eyes usually are held fixed and turned toward the opposite side by the opposing extraocular muscles.

DISTURBANCES OF HORIZONTAL GAZE

Anatomy — The signal for horizontal gaze originates in the contralateral frontal lobe for fast eye movements (saccades) and in the ipsilateral parieto-occipito-temporal region for smooth pursuit. The supranuclear pathway extends to the ipsilateral sixth nerve (abducens) nucleus. The final common pathway for horizontal gaze consists of the pontine reticular formation (PPRF) and the sixth nerve nucleus. The sixth nerve nucleus receives supranuclear and vestibular input to initiate horizontal eye movements.

The sixth nerve nucleus contains two types of neurons: motor neurons and internuclear neurons. The axons of the internuclear neurons cross to the contralateral side in the lower pons and, after ascending in the medial longitudinal fasciculus (MLF), synapse in the portion of the third nerve (oculomotor) subnucleus that innervates the medial rectus muscle. Thus, horizontal gaze involves synchronous activation of the lateral rectus muscle of one eye and the medial rectus muscle of the other, via the MLF. This final common pathway for horizontal gaze is controlled by the vestibular, optokinetic, smooth-pursuit, and saccadic systems [2-7].

A lesion anywhere along the supranuclear or nuclear pathways that control horizontal eye movements can cause a horizontal gaze palsy (table 2). Horizontal pursuit, saccades, or both may be impaired depending upon the location of the lesion. A horizontal gaze palsy to the ipsilateral side occurs in pontine lesions affecting the abducens nucleus and/or the PPRF. Lesions of the MLF result in internuclear ophthalmoplegia (INO), whereas lesions of the MLF plus the ipsilateral abducens nucleus and/or PPRF result in the one-and-a-half syndrome.

Horizontal gaze palsy: Clinical features and causes — Horizontal gaze palsy usually is caused by a contralateral frontal or ipsilateral pontine lesion (table 2).

●Causes – Horizontal gaze palsies are caused by ischemia and infarction, hemorrhage, vascular malformations, tumors, demyelination, trauma, or infections [2,3,8-10].

●Clinical features – Patients with horizontal gaze palsy typically are unable to move either eye beyond the midline in one direction. The eyes are deviated constantly to the opposite side, and patients must turn their head toward the side with the gaze palsy to fixate on an object that is directly in front of them.

Frontal lobe lesions may impair ipsilateral horizontal smooth pursuit, and lesions of the posterior parietal cortex or parieto-occipito-temporal region decrease the amplitude and velocity of smooth-pursuit eye movements toward the side of the lesion.

In patients with pontine lesions involving the PPRF or sixth nerve nucleus, the eyes may be deviated away from the side of the lesion. Thus, patients who are unable to move either eye beyond the midline to the left may have a left pontine lesion, and the eyes are deviated to the right. Patients may have partial horizontal gaze movement if the damage to the pontine structures is only partial.

●Evaluation – At the bedside, pontine lesions usually can be differentiated from supranuclear lesions in the frontal lobe by associated neurologic findings (table 2). The oculocephalic or doll's eye maneuver is helpful. Passive horizontal rotation of the head directly stimulates the sixth nerve nucleus via the vestibuloocular reflex and will overcome gaze palsies induced by frontal lobe lesions but will not overcome gaze palsies caused by pontine nuclear and infranuclear lesions.

Neuroimaging studies should be performed with attention given to the dorsal pons. Magnetic resonance imaging (MRI) usually is the procedure of choice. However, computed tomography (CT) is an acceptable alternative in the acute setting, in patients with altered levels of consciousness, or in patients in whom MRI is contraindicated (eg, patients with pacemakers).

An electroencephalogram (EEG) is indicated to exclude a seizure disorder in patients with clinical seizure activity or intermittent conjugate gaze deviation, or in obtunded or comatose patients.

Internuclear ophthalmoplegia — INO is characterized by adduction weakness on the side of the MLF lesion and nystagmus in the opposite eye (the abducting eye in attempted horizontal gaze) (figure 1). Convergence (ie, both eyes turning in, necessary for near fixation) usually is preserved.

INO is caused by lesions located in the MLF between the sixth nerve nucleus and the contralateral third nerve nucleus (figure 2). Such lesions permit the horizontal gaze center to communicate with the sixth nerve nucleus but not the contralateral third nerve nucleus.

INO is discussed in detail separately. (See "Internuclear ophthalmoparesis".)

One-and-a-half syndrome — Patients with the one-and-a-half syndrome have horizontal gaze palsy when looking to one side (the "one") and impaired adduction (INO) when looking to the other (the "and-a-half").

The one-and-a-half syndrome is caused by a unilateral lesion of the dorsal pontine tegmentum, involving the ipsilateral PPRF, internuclear fibers of the ipsilateral MLF, and, usually, the abducens nucleus.

One-and-a-half syndrome is discussed in detail separately. (See "Internuclear ophthalmoparesis", section on 'One-and-a-half syndrome'.)

DISTURBANCES OF VERTICAL GAZE

Anatomy — The frontal lobes (for saccades), the parietooccipital lobes (for pursuit), and their connections to the brainstem constitute the supranuclear pathway for vertical gaze. The presumed vertical gaze center in the rostral midbrain includes the rostral interstitial nucleus of the medial longitudinal fasciculus (MLF) and the interstitial nucleus of Cajal (INC). The ocular motor neurons concerned with vertical gaze and torsional eye movements originate in the oculomotor and trochlear nuclei, and the third and fourth cranial nerve nuclei, respectively. These nuclei receive afferents from the vestibular, smooth-pursuit, optokinetic, and saccadic systems.

Vertical gaze palsy — A lesion located anywhere along the supranuclear or nuclear pathways that control vertical eye movements can cause a vertical gaze palsy (table 3).

●Causes – Multiple conditions, including midbrain strokes, pineal and metastatic tumors, vascular malformations, hydrocephalus (including shunt failure), inflammation, infection, and demyelinating disorders such as multiple sclerosis, are associated with vertical gaze abnormalities [11,12]. In addition, numerous metabolic disorders, including Bassen-Kornzweig syndrome (abetalipoproteinemia), Niemann-Pick C disease, Tay-Sachs disease, Gaucher disease, maple syrup urine disease, hyperglycinuria, hexosaminidase A deficiency, Wilson disease, kernicterus, and Wernicke syndrome, can produce vertical gaze palsy [13-15]. (See appropriate topic reviews.)

●Clinical features – Paralysis of upward vertical gaze is the most common vertical gaze palsy, followed by paralysis of both upward and downward gaze, and finally paralysis of downward gaze alone.

A patient with paralysis of upward gaze can move the eyes together in all directions, except above the midline. The head usually is tilted backward. The individual may have partial movement of the eyes if the paralysis is incomplete.

●Differential diagnosis – Myasthenia gravis can mimic a vertical gaze paresis and ptosis; symptoms of variability or fatigue should prompt an evaluation for myasthenia gravis. (See "Clinical manifestations of myasthenia gravis".)

●Evaluation – In the absence of a generalized metabolic or degenerative process, magnetic resonance imaging (MRI) with attention given to the mesencephalon, thalamus, and ventricular system is required in patients with vertical gaze palsy. A lumbar puncture should be performed to look for infectious etiologies if MRI is normal and signs suggestive of meningeal irritation are present, or if MRI with contrast reveals diffuse meningeal enhancement.

Parinaud syndrome — The constellation of neuroophthalmologic findings seen with pretectal lesions (including abnormalities of vertical gaze and convergence) (table 4) has been variously called Parinaud syndrome, the Sylvian aqueduct syndrome, the pretectal syndrome, the dorsal midbrain syndrome, and the Koerber-Salus-Elschnig syndrome (picture 1) [16-19].

●Causes – In one study of 206 patients, the etiology was hydrocephalus in 80 patients, stroke in 53, and tumor in 45 [16].

The development of a dorsal midbrain syndrome in a patient with shunted hydrocephalus typically indicates dysfunction of the shunt, and revision of the shunt should be considered even if neuroimaging is normal [17]. (See "Hydrocephalus in children: Management and prognosis", section on 'Shunt malfunction'.)

●Clinical features – In the case series described above, abnormal pupils were found in 198 patients, vertical gaze limitation in 180, disjunctive horizontal eye position in 90, disjunctive vertical eye position in 79, lid retraction in 83, and convergence-retraction nystagmus in 71 [16].

●Differential diagnosis – Bilateral light-near dissociation (seen in Parinaud syndrome), in which the pupils constrict poorly to light but react to accommodation (near response), distinguishes lid retraction related to Parinaud syndrome (Collier sign) from lid retraction related to thyroid disease. (See "Clinical features and diagnosis of thyroid eye disease", section on 'Evaluation'.)

Skew deviation — The term "skew deviation" is reserved for vertical misalignment resulting from supranuclear derangements in the posterior fossa. These lesions disrupt the vestibuloocular connections and may be constant or transient. Otolith inputs to the INC from the contralateral vestibular nuclei, and motor outputs from the INC to cervical and ocular motor neurons, probably are involved [20]. Stimulation of the semicircular canal can produce skew deviation in normal subjects [21].

●Causes – Skew deviation can accompany lesions in different areas of the brainstem (mesencephalon to medulla) or cerebellum. It usually is caused by acute hydrocephalus, tumors, strokes, and multiple sclerosis [22,23].

●Clinical features – Skew deviation consists of downward and inward rotation of the eye on the side of the lesion and upward and outward rotation of the eye on the opposite side. Patients typically manifest other posterior fossa signs (eg, other cranial neuropathies, hemisensory loss, or hemiparesis). In some patients, skew deviation may be associated with ocular torsion and head tilt (a triad of findings known as the ocular tilt reaction). The head tilt represents a compensatory response to the perceived tilt of the subjective visual vertical.

The vertical separation can be tested by placing a red lens over one eye, shining a white point-light at the patient, and asking the patient to note the relative position of the red spot to the white spot. The light should be moved from side to side to see how the separation changes with lateral and vertical gaze. Skew deviation often is "comitant," meaning that gaze direction has little effect upon the distance between the images. When it is incomitant, it needs to be differentiated from other problems, such as fourth cranial nerve palsy. (See "Fourth cranial nerve (trochlear nerve) palsy", section on 'Differential diagnosis'.)

●Differential diagnosis – Superior and inferior oblique palsy also can present with downward deviation, cyclotorsion, and head tilt [21,22,24]. However, in patients with skew deviation, the direction of torsion usually is inconsistent with that of superior or inferior oblique palsy, and additional posterior fossa signs typically are present [22,24]. In addition, cyclotorsion and vertical misalignment are position dependent in skew deviation (decreasing with position change from upright to supine), whereas they are relatively unaffected by position change in superior oblique palsy [25,26]. A positive upright-supine test (vertical strabismus decreases by ≥50 percent with position change from upright to supine) is highly specific (100 percent) and sensitive (80 percent) for skew deviation [26].

SUMMARY

●Terminology – Patients with a gaze palsy are unable to move both eyes past the midline in one direction. The eyes usually are held fixed and turned toward the opposite side by the opposing extraocular muscles. (See 'Terminology' above.)

●Anatomy – Lesions anywhere along the supranuclear or nuclear pathways that control horizontal eye movements can cause a horizontal gaze palsy (table 2). Horizontal pursuit, saccades, or both may be impaired, depending upon the location of the lesion. (See 'Disturbances of horizontal gaze' above.)

●Horizontal gaze palsies – Horizontal gaze palsies may be caused by ischemia and infarction, hemorrhage, vascular malformations, tumors, demyelination, trauma, or infections. (See 'Horizontal gaze palsy: Clinical features and causes' above.)

●Vertical gaze palsies – Lesions anywhere along the supranuclear or nuclear pathways that control vertical eye movements can cause a vertical gaze palsy (table 3).

Paralysis of upward vertical gaze is the most common vertical gaze palsy, followed by paralysis of both upward and downward gaze, and finally paralysis of downward gaze alone. (See 'Vertical gaze palsy' above.)

Vertical gaze abnormalities may be associated with multiple conditions, including midbrain strokes, pineal and metastatic tumors, vascular malformations, hydrocephalus (including shunt failure), inflammation, infection, demyelinating disorders such as multiple sclerosis, and metabolic disorders. (See 'Vertical gaze palsy' above.)