In the cavernous sinus, the oculomotor nerve is located dorsal to the trochlear nerve, and both nerves lie in the deep layer of the lateral wall of the sinus. In the anterior cavernous sinus, the nerve divides into superior and inferior trunks, which become distinct near the orbital apex. The superior division is smaller and supplies the superior rectus and the levator palpebrae superioris. The inferior division sends branches to the medial rectus, inferior rectus, inferior oblique, and ciliary ganglion. Although divisional palsies are usually caused by superior orbital fissure or orbital lesions, it is now well established that more proximal fascicular lesions can also produce divisional paralysis, because the segregation of oculomotor fibers is maintained at the fascicular level.204,370 The only location in which a divisional palsy cannot occur is in the nucleus.369

Clinical Features

Injury to the oculomotor nerve may result in complete or partial weakness of any or all of the muscles it innervates. In complete oculomotor palsy, the eye is markedly exotropic and mildly hypotropic with complete ptosis and pupillary dilation. There is no elevation, depression, or adduction, and a characteristic intorsion on attempted downgaze reveals the residual presence of superior oblique function. Ptosis is often the most prominent clinical sign and the first to resolve. Contrary to earlier beliefs and anecdotal observations,274,584 a dedicated study found that relaxation of the rectus muscles in oculomotor and abducens palsies does not produce measurable proptosis.246 Nevertheless, we have seen patients in whom unilateral oculomotor palsy produced a slight proptosis, thereby simulating an orbital lesion.

The vertical rectus muscles are the primary elevators and depressors and remain so even in adduction. A pathological process that is uniformly distributed across the fibers of the oculomotor nerve causes little vertical deviation of the affected eye in its exotropic position because the superior oblique muscle has a primarily torsional action in this position. Therefore, a significant hypotropia in this position suggests that the inferior divisional fibers are preferentially affected. As the eye moves into adduction, the depression vector of the superior oblique muscle becomes more prominent, and the eye may become increasingly hypotropic. When the inferior division of the third nerve is primarily affected, the eye lies in an exotropic position due to involvement of the medial rectus muscle and be hypertropic due to inferior rectus paresis (Fig. 6.1). If the superior division is injured, the eye is hypotropic in any position of gaze. Injury to the inferior oblique muscle causes intorsion of the globe, which may produce torsional diplopia and disrupt fusion once ocular alignment is re-established.53

Unilateral oculomotor palsy also leads to central adaptations in the vestibulo-ocular reflex, such as reduced abduction and incyclotorsional gains. These secondary adaptations function to reduce asymmetrical movement of the retinal images during head motion, reduce retinal image disparity, and prevent nystagmus.602

Partial Forms of Oculomotor Palsy

Isolated Inferior Rectus Muscle Palsy

Isolated inferior rectus palsy is a well recognized condition thathasasurprisinglybroaddifferentialdiagnosis443,464,526,558,575 (Table 6.1). The child with inferior rectus palsy usually complains of vertical diplopia that increases in downgaze. On examination, the child manifests an incomitant hypertropia that increases in downgaze. Although some children show a classic three-step test (Fig. 6.2), von Noorden and Hansell575 have stressed that the three-step test should not be relied upon to confirm the diagnosis of inferior rectus palsy. Children with acquired inferior rectus palsy may show either incyclotropia of the involved eye or excyclotropia of the opposite eye when tested with the Double Maddox Rod, while children with congenital inferior rectus palsy may have an absence of subjective cyclotropia.575

The infrequent occurrence of isolated inferior rectus palsy reflects the complex neuroanatomy of the oculomotor nerve.464 Most compressive, ischemic, and inflammatory third nerve lesions affect the portion of the nerve located between the oculomotor nucleus in the dorsal midbrain and its bifurcation into superior and inferior divisions in the anterior cavernous sinus, where axons destined to innervate all extraocular muscles served by the oculomotor nerve are closely bundled. Such injuries generally produce divisional or incomplete palsies.

Neuroanatomically, there are two sites in which a third nerve injury can produce an isolated paralysis of the inferior rectus muscle.523 One site is the oculomotor nucleus, where cell bodies of neurons for each muscle are segregated into distinct subnuclei. A focal vascular, demyelinating, or metastatic lesion involving the inferior rectus subnucleus can result in isolated inferior rectus palsy. The orbit is the second site, where an injury or disease process involving either the branch of the inferior oculomotor division destined for the inferior rectus muscle, the myoneural junction, or the muscle itself could produce an isolated inferior rectus palsy.523 Myasthenia gravis is the primary diagnostic consideration in a child with unilateral inferior rectus palsy and no history of orbital trauma. With the use of orbital MR imaging, cases of unilateral inferior rectus aplasia are increasingly recognized.

Fig. 6.1  Inferior divisional paresis of right oculomotor nerve

Table 6.1  Differential diagnostic considerations of unilateral inferior rectus palsy in childhood

Myasthenia gravis

Orbital disease (blowout fracture, orbital inflammation, or tumor) Iatrogenic (following retrobulbar injection, inferior oblique myectomy,

blepharoplasty) Nuclear third nerve palsy Congenital

Idiopathic

Isolated Inferior Oblique Muscle Palsy

Isolated inferior oblique palsy is rare. Most children who present with a limitation of elevation in adduction have a congenital restriction involving the superior oblique tendon (Brown syndrome). The distinction between inferior oblique palsy and Brown syndrome is primarily based on three features: (1) In inferior oblique palsy, there is marked overaction

of the antagonist superior oblique muscle with correllary intorsion of the affected eye; while in Brown syndrome, there is little, if any, superior oblique muscle overaction or associated torsion. (2) In inferior oblique palsy, there is a large A pattern; while in Brown syndrome, the eyes remain horizontally aligned until the patient looks into far upgaze, where a large exotropia develops (Y pattern). (3) Inferior oblique palsy is usually associated with a negative forced duction test, whereas a positive forced duction test is considered the sine qua non of Brown syndrome.

The three-step test in a right inferior oblique palsy would show a right hypotropia that is worse in left gaze and when the head is tilted to the left. Jampolsky252 has found a tight superior rectus muscle to be a common cause of a positive forced head tilt test. An isolated tight left superior rectus muscle produces a pattern on the three-step test that is indistinguishable from a right inferior oblique palsy. However, it may be impossible to determine whether the tight contralateral superior rectus muscle is the primary problem or a secondary consequence of inferior oblique palsy. Inferior adhesions following trauma or surgery can also produce restrictive changes that simulate inferior oblique palsy.249 A report of a transient isolated inferior oblique paresis accompanied by mydriasis and accommodative palsy in a 15-year- old boy after sinus surgery was probably attributable to damage to the inferior division of the oculomotor nerve.43

Pollard437 reported a series of 25 cases of presumed inferior oblique palsy seen over a 17-year period. No systemic

cause was identified, and most underwent successful surgery. Most patients with inferior oblique palsy can be successfully treated with a weakening procedure (spacer, tenotomy or recession) of the antagonist superior oblique muscle, with a low risk of postoperative trochlear nerve palsy. If intraoperative forced duction testing reveals a tight contralateral superior rectus muscle, consideration should be given to recessing this tight muscle instead of superior oblique weakening. Khawam et al279 have used ipsilateral superior oblique tenotomy or tenectomy in combination with recession of the contralateral superior rectus muscle.

Since pupillary fibers are known to travel with the nerve to the inferior oblique muscle, how can an isolated inferior oblique palsy occur in the absence of pupillary involvement? Within the oculomotor nucleus and fascicle, neurons and corresponding axons destined for the inferior oblique muscle are situated most laterally, while those destined for the pupil are situated medially.95 Isolated inferior oblique paresis has been documented to arise from lateral fascicular injury to the oculomotor nerve.95 Selective involvement could of the inferior oblique fibers occur in the region of the nucleus or fascicle, or in the orbit after the pupillary fibers branch off to the ciliary ganglion. Despite prevailing doubts and the existence of simulating conditions, the recent finding of reduced inferior oblique muscle diameter on MR imaging suggests that isolated inferior oblique palsy (or hypoplasia) is indeed a distinct entity.154

Isolated Internal Ophthalmoplegia

Intermittent unilateral pupillary mydriasis can occur in the absence of other motility deficits in the setting of an otherwise uncomplicated migraine headache.369 However, when headache and mydriasis are accompanied by extraocular muscle paresis or ptosis, an intracranial aneurysm must be ruled out.77 Compressive lesions of the oculomotor nerve occasionally produce unilaterally impaired accommodation as the initial symptom. The finding of intermittent exotropia in the child with isolated internal ophthalmoplegia should lead to suspicion of early oculomotor palsy.21

Cholinergic supersensitivity of the iris sphincter may develop in any oculomotor palsy with pupillary involvement.245 Other clinical signs usually attributed to postganglionic damage (light-near dissociation, segmental sphincter palsy) may also be seen;245,247 however, these signs arise too quickly to be explained by transsynaptic degeneration and are now believed to be a direct consequence of sphincter denervation.247 The presence of supersensitivity is not related to the severity of the third cranial nerve dysfunction or to the time between onset and testing, but to the extent of the associated iris sphincter palsy and to the extent of anisocoria.247

Isolated internal ophthalmoplegia has many causes.21 In one patient who sustained head trauma, biopsy demonstrated selective tearing of the medial aspect of the third cranial nerve.342 Wilhelm et al590 described a 19-year-old woman with isolated internal ophthalmoplegia, diagnosed as Adie’s pupil, who was found 14 years later to have an oculomotor neurinoma. Werner et al590 described a 10-month-old infant with internal ophthalmoplegia and cholinergic supersensitivity as the only sign of third cranial nerve compression by a cisternal endodermal cyst.

Isolated Divisional Oculomotor Palsy

Most cases of superior branch oculomotor palsy have been reported in adults.67,141,159,204,266,304,350 Isolated superior division oculomotor palsy is extremely rare in children. Saeki et al479 described a 10-year-old boy who developed a superior division oculomotor palsy 1 week after a flu-like illness. The palsy spontaneously resolved over 2 months. Isolated inferior divisional oculomotor nerve palsy is usually reported in adults as a posttraumatic or idiopathic phenomenon.130,486,538

Oculomotor Synkinesis

Oculomotor synkinesis, or aberrant reinnervation, can arise a few weeks to months following an oculomotor nerve injury.

Oculomotor synkinesis most frequently results from trauma, tumors, and aneurysms, which involve the physical disruption of axons; however, it also accompanies some congenital cases.589 It is not a feature of ischemic oculomotor palsy. The major signs of aberrant regeneration of the oculomotor nerve169 include:

•Pseudo-von Graefe sign: retraction of the eyelid on attempted downgaze;

•Horizontal gaze eyelid synkinesis: elevation of the eyelid on attempted adduction of the affected eye;

•Limitation of elevation and depression of the eye, with occasional retraction of the globe on attempted vertical movements;

•Adduction of the affected eye on attempted elevation or depression;

•Pseudo-Argyll Robertson pupil: the affected pupil reacts poorly and irregularly to light stimulation but will constrict on adduction;

•Monocular vertical optokinetic responses: the normal eye responds normally, but the involved eye shows poor vertical responses.

Three mechanisms have been proposed to explain abnormal muscular synkinesis.37,327 These include peripheral misdirection at the site of injury, ephaptic transmission, and central reorganization of motoneurons and their inputs.

In peripheral misdirection, neuronal sprouts grow indiscriminately from the motor nucleus or proximal portion of the nerve following an acute injury. These nerve fibers make erroneous alignments in peripheral nerve sheaths and, thereby, arrive at a muscle that does not correspond to the musculotopic localization of their cell bodies. Bielschowsky52 suggested that peripheral misdirection may cause oculomotor synkinesis, and contemporary investigators continue to consider it the most common mechanism.

Neuroanatomical tracer studies have been conducted in an experimental model of oculomotor nerve injury, which documents anomalous connections between the somatic motoneurons of the oculomotor nucleus and the ipsilateral superior rectus muscle.515 The superior rectus muscle in this model (cat) is normally 98% innervated by the contralateral nucleus, as is the case in primates. These studies show that after oculomotor injury and partial recovery, neurons terminating in the superior rectus muscle originate from regions of the ipsilateral oculomotor nucleus that previously innervated the inferior rectus, medial rectus, and inferior oblique muscles, thus supporting the peripheral misdirection hypothesis. Similar studies have been conducted on skeletal muscle and in facial synkinesis with similar conclusions.33,82 Naturally occurring facial nerve injury with motor synkinesis in a primate has also been shown to be due to peripheral misdirection by tracer studies.33

Ephaptic transmissions denote a propagation of neural impulses between adjacent cells by an electrotonic mechanism,