Disorders of the Ocular Motor Cranial Nerves and Extraocular Muscles

Lid Function

Ptosis can be quantified using the following methods:

• 1.

  Measure the distance between the upper lid margin and the midcorneal reflex when the globe is in normal primary position. Ptosis is present when this distance is <2 mm or varies by more than 2 mm between the eyes.

• 2.

  Measure the amount of the superior portion of the cornea covered by the upper lid when the globe is in primary position; normal is approximately 2 mm. With ptosis, more than 4 mm of cornea is covered.

• 3.

  Measure the vertical width of the palpebral fissure; it is normally approximately 9–15 mm.

Pupil

Assess pupil size and reactivity. If anisocoria is present, it should be observed under varied illumination; in Horner syndrome, the anisocoria is more apparent in darkness and a lag in pupillary dilation may be observed, whereas with pupillary constrictor paresis, the difference is more evident under bright light. A relative afferent pupillary defect, indicating optic nerve dysfunction, is detected by swinging a bright light source from one pupil to the other, watching for dilation in the affected eye. Slit lamp examination may identify sectoral irregularities in the iris, an indication of reinnervation.

Ocular Alignment

Assess ocular alignment by the alternate cover test or Maddox rod testing. A patient with a phoria prefers to fixate with one eye and will shift eye position only when the preferred eye is covered; if a tropia is present, fixation will shift when either eye is occluded. The degree of horizontal or vertical misalignment can be quantified using prisms. The Bielschowsky three-step test is valuable for identification of trochlear nerve palsies (see “Trochlear Palsy (CN IV)” section). Information as to whether ocular misalignment is long-standing may be obtained via stereoacuity tests.

Ductions

Assess ductions by having the patient follow a hand-held target to all cardinal positions of gaze; observe the range, speed, and smoothness of these movements in each eye, as well as whether the two eyes move conjugately. The examiner can best observe both eyes simultaneously by fixating on the patient’s nose. When there is limitation of movement to a given position of gaze, it may be difficult to distinguish between weakness of an EOM (e.g. lateral rectus) and restriction or overaction (or both) of its antagonist (medial rectus). The speed and smoothness of movement may serve as a clue; sudden slowing toward the end of an excursion suggests restriction of the antagonist. The definitive tests, however, are those of forced duction and active force generation. Forced duction testing is performed by grasping the anesthetized extraocular muscle, tendon, or globe itself, and pulling it through its range of motion; the examiner directly feels any mechanical restriction. In young children, this procedure often requires general anesthesia. Active force generation requires the alert patient’s cooperation to attempt eye movements while the examiner grasps muscle, tendon, or globe and senses muscle force.

Horizontal and Vertical Saccades

Assess horizontal and vertical saccades by asking the patient to rapidly switch fixation between the examiner’s nose and targets held in each extreme of the visual field. Slow saccades suggest muscle weakness or, in the case of the medially directed saccades, an internuclear ophthalmoplegia; saccades that begin rapidly but slow toward the end of their excursion suggest restriction of the opposing EOM. Repeated saccades may reveal the fatigability associated with myasthenic syndromes. Hyper- or hypometric saccades suggest cerebellar disease. Occasionally, disturbances in smooth pursuit suggest a particular pattern of EOM involvement—for example, the upshoot seen during medial pursuit in Duane’s syndrome (see below). Both horizontal and vertical head thrusts take advantage of vestibular input to indicate the true range of motion of the eyes where voluntary maneuvers fail to do so; in addition, they provide helpful information about central control of eye movements. Identification of nystagmus indicates central dysfunction but may also provide an indirect indication of limitation, such as with the abducting nystagmus seen when medial deviation of the opposite eye is limited.

Finally, additional general ophthalmologic testing assists in identifying visual pathway dysfunction that may affect ocular motility. This testing may include assessment of visual acuity at far and at near, color perception, the visual fields, and the funduscopic appearance of the optic nerves and the central and peripheral retina. The latter also may be particularly helpful to identify complex neurologic syndromes of which abnormal EOMs are a single component.

Anatomy

The oculomotor nucleus consists of a series of closely associated subnuclei arranged along the dorsal-ventral and rostral-caudal dimensions of the tectum of the midbrain (see Figure 46.3 ). A midline dorsal and caudal subnucleus provides bilateral innervation to the levator palpebri. Together with the contralateral axons from the superior rectus subnucleus, these axons form the superior division of the nerve. All EOMs other than the superior recti are innervated ipsilaterally via the inferior division of the nerve. Pupillary fibers emerge from the single midline Edinger-Westphal nucleus in the complex, and run superficially within the nerve fascicle to the ipsilateral ciliary muscle and iris sphincter.

Localizing Syndromes

The anatomy of the oculomotor nuclei and nerve produces clinical features helpful in the localization of oculomotor palsies. Third nerve palsies can be localized to the nucleus if they include contralateral involvement of the superior rectus and bilateral involvement of the levator palpebri (and probably also of the medial recti). They may localize to the nerve if ptosis and ophthalmoplegia are ipsilateral, and to only the superior division of the nerve if the ophthalmoplegia is limited to vertical limitations as seen in CFEOM (see the following). Given the close proximity of the oculomotor nucleus to other brainstem structures, acquired nuclear lesions are often associated with other neurologic signs such as somnolence and hemiplegia. Lesions affecting the oculomotor nerve fascicle cause ipsilateral signs because the axons serving the superior recti have already decussated within the nuclear complex. Because the oculomotor nerve fibers pass through the reticular formation, red nucleus, and substantia nigra, a lesion along their course may lead to ipsilateral ataxia (dentatorubrothalamic tract) or contralateral hemitremor, hemichorea, or hemiballismus (red nucleus and substantia nigra). In the interpeduncular cistern, CN III may be subject to compression from aneurysms, although this is very rare in childhood. Early involvement of the pupil in oculomotor palsies points to compressive lesions, as the dorsomedial placement of the pupillary fibers in the nerve fascicle renders them susceptible to compression.

Just before entering the cavernous sinus, the third nerve is susceptible to compression at the free edge of the tentorium and the clivus. Uncal herniation generally causes an ipsilateral, and rarely a contralateral, oculomotor palsy in which the pupil is involved early. Ipsilateral involvement of CN III, CN IV, and CN VI localizes to the cavernous sinus or orbital apex. Involvement of the trigeminal nerve is often more extensive with cavernous sinus lesions, whereas the presence of proptosis or visual loss from optic neuropathy, or both, defines the orbital apex syndrome. In the cavernous sinus, the nerve lies dorsally and deep in the lateral wall, superior to the trochlear nerve; as it enters the superior orbital fissure, it divides into superior and inferior divisions. The superior division innervates the superior rectus and levator palpebrae superioris, whereas the inferior division innervates the inferior and medial recti, inferior oblique, and ciliary ganglion. Thus, an isolated superior division palsy causes globe depression and ptosis, whereas an isolated inferior division palsy results in abduction, elevation, and mydriasis. Lesions at the apex or within the superior orbital fissure typically produce divisional palsies, but because the fibers are segregated within the nerve along much of the fascicular course, more proximal lesions can also produce these findings.

Fundamental Signs and Symptoms

Oculomotor palsies classically present with ptosis, mydriasis, and external ophthalmoplegia. With a complete third nerve palsy, the pupil is large and does not constrict to light or vergence efforts, and near accommodation is impaired. The affected eye is depressed and abducted, and limited in adduction and elevation. Ptosis is severe. Correspondingly, patients complain of ptosis, blurred vision especially at near (due to inability to accommodate sufficiently), and diplopia.

Although the major clinical features are the same in congenital and acquired forms of oculomotor palsy, subtle differences in presentation (e.g. presence of amblyopia, synkinesis, pupillary involvement, or fluctuating symptomatology) may help distinguish the two forms.

Etiology

Third nerve palsies are rare, and less common than fourth or sixth nerve palsies in childhood. About ⅔ are partial, and ⅓ complete. As many as 47% of all pediatric oculomotor palsies are congenital. Acquired causes include trauma (12–37%), infection and other inflammation (6–21%), tumor (3–17%), and migraine (3–9%). Aneurysms and other vascular events account for 3% to 11%. The cause remains undetermined less often in children (2–14%) than in adults (25–32%).

Acquired CN III Palsies

Acquired oculomotor palsies are more often partial than complete, and may be isolated or associated with more generalized neuromuscular processes ( Table 46.2 ). The most common causes of oculomotor palsies are trauma (up to 72%), neoplasm (5–31%), inflammation or infection (9–25%), migraine (7–19%), and other vascular pathologies (3–13%). As many as 20% of cases are cryptogenic. Painful ophthalmoplegia often involves more than one cranial nerve, and suggests acquired conditions such as infection, tumor, orbital pseudotumor, hemorrhage, thrombosis, aneurysm, or Tolosa-Hunt syndrome. In contrast, synkinesis or sparing of the pupil suggests a more benign cause. Diplopia in acquired oculomotor palsy is usually oblique in primary position, but varies with the relative degree of weakness in each muscle, and may be obscured if ptosis is severe enough to occlude the paretic eye. Although intorsion due to inferior oblique involvement is not often detected clinically, the patient may perceive a tilted sense of vertical (not always in the paretic eye or in the expected direction).

Table 46.2

Etiology of Acquired Ocular Motor Palsies in Childhood

Etiology	III Cranial Nerve	IV Cranial Nerve	VI Cranial Nerve
TRAUMA	25–72%	8–50%	20–42%
Diffuse axonal injury	+
Ischemic	+
Shearing forces	+	+	+
Subdural hematoma	+		+
Cavernous sinus thrombosis	+	+	+
Postoperative	+	+	+
NEOPLASIA	5–31%	Rare	17–39%
Cavernous sinus
Meningioma	+	+	+
Schwannoma	+	+	+
Pituitary fossa
Pituitary adenoma	+	+	+
Craniopharyngioma	+	+	+
Dermoid/epidermoid	+	+	+
Teratoma	+	+	+
Sellar germ cell tumor	+	+	+
Cerebellar
Astrocytoma		+	+
Medulloblastoma		+	+
Brainstem glioma	+	+	++
Other neoplasms
Pinealoma		+	+
Meningioma		+	+
Schwannoma		+	+
Acoustic neuroma		+	+
Ependymoma		+	+
Nasopharyngeal carcinoma		+	+
Clivus chordoma
Infiltrating neoplasms
Leptomeningeal sarcoma	+	+	+
Lymphoma	+	+	+
Carcinomatous meningitis	+	+	+
Mesencephalic cyst	+
VASCULAR	3–13%		1–2%
Subdural hemorrhage	+	+
Aneurysm	+	+	+
Cavernous hemangioma	+	+	+
Arteriovenous malformation	+	+
Carotid-cavernous fistula			+
INFECTION	9–25%
Meningitis	+	+	+
Encephalitis	+	+	+
Mastoiditis, Gradenigo’s syndrome			+
INFLAMMATORY
Sarcoidosis	+	+	+
Tolosa-Hunt syndrome	+	+	+
Orbital pseudotumor	+	+	+
RHEUMATOLOGIC/AUTO-IMMUNE
Polyarteritis nodosa	+
Multiple sclerosis, ADEM	+	+	+
Guillain-Barré syndrome	+	+	+
Sjögren’s syndrome		+
OTHER
Migraine	7–19%		+
Toxins	+	+
Increased intracranial pressure		+	+
Thyroid eye disease	+	+	+
Iatrogenic	+	+
Cryptogenic	<20%	0–21%	9–36%

ADEM=acute disseminated encephalomyelitis.

Acquired partial oculomotor palsies suggest pathology at extremes of the oculomotor nerve: either discrete lesions in the midbrain, involving an oculomotor subnucleus, or focal intraorbital lesions. Nuclear causes include focal metastasis, ischemia, or demyelination, while orbital causes include myasthenia gravis, trauma, tumor, or inflammation.

Recurrent transient oculomotor palsies in childhood are most commonly due to ophthalmoplegic migraine. This uncommon inflammatory cranial neuropathy is much more frequent in children than adults. Onset is generally before age 10. Each episode typically begins with a severe ipsilateral hemicranial headache, with ophthalmoplegia developing within hours to days (rarely up to 14 days), and generally resolving after 3 to 4 days. Deficits rarely persist as long as a month, and synkinesis may develop. Although a complete oculomotor palsy is most frequent, isolated pupillary involvement can occur, and involvement of the fourth and sixth cranial nerves, oculomotor divisions, and levator palpebrae are also reported in ophthalmoplegic migraine. Rarely, recurrent ophthalmoplegia may occur in the absence of headache, in what may represent a migraine equivalent. Magnetic resonance imaging (MRI) studies commonly show enlargement and contrast enhancement of the interpeduncular portion of the oculomotor nerve during, and occasionally following, ophthalmoplegic migraines ( Figure 46.4 ), while the CSF examination is normal.

Tolosa-Hunt syndrome is an acute syndrome of orbital pain and ophthalmoplegia caused by granulomatous inflammation within the cavernous sinus or orbit, which responds rapidly and dramatically to oral steroids but may recur. Myasthenia gravis should be suspected whenever ptosis or diplopia fluctuate in severity.

Anatomy

The trochlear is the only cranial nerve to emerge from the dorsal aspect of the brainstem, the only one to cross completely, and the longest and thinnest of the ocular motor nerves. The trochlear nucleus is located ventral and lateral to the Sylvian aqueduct at the level of the inferior colliculus, dorsal to the medial longitudinal fasciculus and caudal to the oculomotor nuclear complex. The nerve fascicle leaves the nucleus, courses along the aqueduct, crossing in its roof inferior to the inferior colliculus, and exits the dorsal midbrain contralateral to the nucleus. The cisternal portion travels laterally around the midbrain to its ventral aspect, then passes along the free edge of the tentorium and along the lateral aspect of the clivus to enter the cavernous sinus. Here, it lies in the lateral wall just inferior to the oculomotor nerve, entering the orbit through the superior orbital fissure and running medially across the superior rectus muscle to the superior oblique muscle.

Localizing Syndromes

Associated neurologic signs aid localization of fourth nerve lesions. The dorsal midbrain syndrome, or Parinaud syndrome, may include trochlear palsy with upgaze weakness, downgaze limitation, convergence spasm, convergence-retraction nystagmus, lid retraction, light-near dissociation, or a combination of these symptoms. A contralateral Horner syndrome or intranuclear ophthalmoplegia indicates involvement of the fourth nerve within the midbrain. Ipsilateral limb ataxia or contralateral sensory loss may reflect involvement of the cerebellar peduncle or sensory lemniscus, respectively. Concurrent involvement of the third and fourth nerves may localize to the midbrain, the cavernous sinus or orbital apex, where the trigeminal nerve may also be affected.

Fundamental Signs and Symptoms

In children, fourth nerve palsy often presents with a head tilt away from the affected eye. This helps neutralize the vertical diplopia and rotation of the image from the paretic eye that the patient will perceive with the head erect and gaze in primary position. In addition to the direction of head tilt, the patient’s perception in primary position, as well as version testing, will localize the paretic eye. Viewing a horizontal edge, the patient may perceive two images of the edge tilted with respect to one another, and intersecting as if forming an arrow that points to the paretic side. This is less common in children than adults and is not found in congenital trochlear palsies.

The Bielschowsky Three-Step Test helps to differentiate between trochlear palsy and its mimickers, such as dissociated vertical deviation, skew deviation, and double elevator palsy ( Table 46.3 ).

Etiology

Most trochlear palsies are congenital (refer to Congenital Cranial Dysinnervation Disorders section below) or arise as a result of trauma. Differentiation between congenital and acquired trochlear palsy may be difficult because the congenital form is often well compensated and thus asymptomatic prior to adolescence or adulthood, when it may decompensate and be mistaken for an acute palsy. Review of photographs from infancy may reveal a long-standing head tilt, suggesting a congenital lesion. Facial asymmetry, with retrusion and upslanting of the mouth on the side of the head tilt, is also indicative of chronicity. Children with congenital trochlear palsy do not generally perceive a tilted image, presumably due to a combination of the head tilt and more complex central physiologic mechanisms. Similarly, amblyopia is rare because the compensatory head tilt enables fusion of the images from both eyes. MRI findings can also be helpful in distinguishing congenital and acquired trochlear palsies . Finally, forced duction testing reveals decreased resistance of the superior oblique in congenital palsies, and normal resistance in acquired forms.

Up to 50% of acquired pediatric trochlear nerve palsies are due to trauma or neurosurgery (see Table 46.2 ). Orbital fractures may damage the nerve, tendon, trochlea, or the muscle itself. Trauma may also cause decompensation of a congenital palsy. Acquired bilateral trochlear palsy is most often due to trauma, and is thought to result from injury at the fascicular decussation. Such cases usually present with a chin-down head position, rather than a head tilt, and with a right hypertropia in left gaze and a left hypertropia in right gaze (alternating adducting hypertropia). A V-pattern esotropia is generally present, and is often large.

Inflammatory and infectious causes of trochlear palsies include the Tolosa-Hunt and Guillain-Barré syndromes, Herpes zoster ophthalmicus, and, less commonly, sarcoidosis and even tetanus. Recurrent CN IV weakness may be seen in the Tolosa-Hunt syndrome, sarcoidosis, ophthalmoplegic migraine (see earlier discussion), and a familial syndrome involving multiple recurrent cranial nerve palsies.