Oculomotor Nucleus

In addition to potentially causing ipsilateral weakness of the medial rectus, inferior rectus, and inferior oblique muscles, an oculomotor nuclear lesion may result in bilateral superior rectus weakness. Ipsilateral subnucleus involvement affects the contralateral superior rectus. This occurs because of the completely crossed nature of superior rectus innervation, with a single superior rectus subnucleus containing fibers destined to decussate to the contralateral side. A unilateral oculomotor nuclear lesion may affect these unilateral originating fibers destined for decussation and those fibers that originated contralaterally and have already decussated. If the single midline levator palpebrae superioris subnucleus is involved in an oculomotor nuclear lesion, bilateral ptosis results. Isolated bilateral ptosis or isolated paresis of a single extraocular muscle are also possible from a small focal nuclear lesion, given the functional division of the subnuclei (Rabadi and Beltmann, 2005). Involvement of the rostral and dorsally located Edinger-Westphal nucleus will lead to pupil involvement. Common brainstem lesions include ischemia, hemorrhage, demyelination, infectious and noninfectious inflammation, and neoplasm.

Oculomotor Palsy Appearance

Identification of a complete third nerve palsy is straightforward on examination, with an ipsilateral eye that is deviated inferiorly and laterally, ipsilateral ptosis, and an ipsilateral enlarged and nonreactive pupil (Fig. 70.2). Great emphasis is placed on the presence of pupil involvement versus pupil sparing with regard to potential lesion etiology. Pupillary fibers are located superomedially near the surface of the nerve and are particularly prone to compression by a PCOM aneurysm. An enlarged, poorly reactive pupil is a key diagnostic feature helpful in distinguishing this entity from an intrinsic nerve lesion such as microvascular ischemia. Relative pupil involvement with an average of 0.8 mm of anisocoria may be seen in up to a third of patients with microvascular oculomotor nerve ischemia, but the pupil generally remains reactive in this scenario (Jacobson, 1998). In rare patients with microvascular ischemia, anisocoria of up to 2 mm may be present, prompting urgent evaluation (Chou et al., 2004). Relative pupil involvement is also commonly seen with mass lesions compressing the nerve (Jacobson, 2001).

Fig. 70.2 Traumatic left oculomotor palsy 3 months following a motor vehicle accident with closed head injury and loss of consciousness. Patient initially had complete left ptosis and complete absence of adduction, elevation, and depression. Results of magnetic resonance imaging and magnetic resonance angiography were normal. A, Central position with slight left ptosis, exotropia (outward deviation), and left pupillary enlargement. B, Impaired adduction of left eye with right gaze. Note aberrant regeneration with anomalous elevation of left lid upon adduction of left eye. C, Normal left gaze. D, Significant impaired elevation of left eye with upgaze. E, Impaired depression of left eye with downgaze.

Brainstem Fascicle

Claude syndrome is the combination of an ipsilateral oculomotor nerve palsy and contralateral ataxia (Liu et al., 1994) (Table 70.1 and Videos 70.1 and 70.2 [available at www.ExpertConsult.com]). Although historically thought to involve the oculomotor fascicle and the red nucleus, the ataxia is likely due to involvement of the superior cerebellar peduncle at the caudal end of the red nucleus (Seo et al., 2001). Nothnagel syndrome is the combination of ipsilateral oculomotor nerve palsy and ipsilateral cerebellar ataxia from involvement of the oculomotor fascicle and superior cerebellar peduncle (see Table 70.1). Weber syndrome is the combination of an ipsilateral fascicular oculomotor nerve palsy and contralateral hemiparesis from cerebral peduncle involvement (see Table 70.1). Benedikt syndrome involves the oculomotor fascicle and red nucleus, causing an ipsilateral oculomotor nerve palsy and contralateral chorea or tremor (see Table 70.1). Common brainstem lesions include ischemia, hemorrhage, demyelination, infectious and noninfectious inflammation, and neoplasm.

Table 70.1 Named Cranial Nerve Syndromes

↓, Decreased.

* Descriptions of named syndromes vary slightly depending on reference used.

Interpeduncular Fossa and Subarachnoid Space: PCOM Aneurysm

The most common etiology of oculomotor dysfunction in this region is compression by a PCOM aneurysm (Trobe, 2009). Identification of a pupil-involving oculomotor palsy requires urgent evaluation for a PCOM aneurysm, given the high risk for subarachnoid hemorrhage and mortality if left undiagnosed and untreated. Involvement of all oculomotor-supplied muscles in the setting of a normal pupil is very unlikely to result from aneurysmal compression; however, the presence of incomplete or partial impairment of the oculomotor muscles even in the setting of a normal pupil should prompt investigation for an aneurysm (Chou et al., 2004). Some patients with an aneurysmal incomplete third nerve palsy will lack pupillary involvement at initial presentation, but the majority will progress to pupillary involvement within 1 week. Spontaneous improvement in third nerve function preceding aneurysm treatment is reported and should not preclude diagnostic testing. Onset of oculomotor dysfunction following minor trauma should also prompt investigation for an underlying aneurysm (Levy et al., 2005; Walter et al., 1994) (see Fig. 70.2). Magnetic resonance angiography (MRA) and computed tomographic angiography (CTA) have largely supplanted conventional cerebral angiography as the preferred diagnostic tests for aneurysm detection, but expert interpretation of these studies requires a high level of experience, skill, and time (Chaudhary et al., 2009; Elmalem et al., 2011). Neither MRA nor CTA is known to be 100% sensitive, and the risks of conventional angiogram are still warranted when strong clinical suspicion for a PCOM aneurysm is present.

In the subarachnoid space, the oculomotor nerve passes in close proximity to the medial temporal lobe. Herniation of the temporal lobe uncus secondary to increased intracranial pressure may result in compression of the oculomotor nerve, manifested clinically as sudden enlargement and poor reactivity of the ipsilateral pupil—the Hutchison pupil. Oculomotor nerve involvement in the interpeduncular fossa and subarachnoid space may also occur secondary to inflammatory or neoplastic meningitis. Enlargement and enhancement of the nerve are usually present on MRI in ophthalmoplegic migraine (see Chapter 69). Oculomotor palsy in meningitis may occur in isolation or be accompanied by signs of meningeal inflammation such as meningismus or additional cranial nerve palsies.

Cavernous Sinus: Tolosa-Hunt Syndrome

An oculomotor palsy in this location may occur in isolation or accompanied by dysfunction of other structures located here, including the abducens and trochlear nerves, the first and second divisions of the trigeminal nerve, and sympathetic fibers. Tolosa-Hunt is a painful syndrome of idiopathic self-limited inflammation of the cavernous sinus, typically responsive to corticosteroids (see Table 70.1 and Videos 70.3 and 70.4 [available at www.ExpertConsult.com]). Cavernous sinus infiltration by metastatic disease is clinically and radiographically identical to Tolosa-Hunt syndrome and should be suspected in older patients. Cavernous sinus lymphoma is typically steroid responsive and should be considered, especially if disease recurs with corticosteroid taper. Inflammation associated with systemic rheumatological disease, nasopharyngeal neoplastic infiltration, carotid-cavernous fistulas, and compression from an intracavernous internal artery aneurysm or meningioma may also cause a cavernous sinus syndrome (Nallasamy et al., 2010). Pituitary apoplexy should be considered in the differential diagnosis for sudden-onset painful unilateral or bilateral oculomotor palsies, with or without accompanying visual loss (Dubuisson et al., 2007).

Orbital Apex

Oculomotor dysfunction in this location is typically accompanied by dysfunction of neighboring structures including the abducens and trochlear nerves, the first division of the trigeminal nerve, and the optic nerve. Features of orbital disease such as proptosis, chemosis, and conjunctival injection may be present. Idiopathic inflammation (orbital inflammatory pseudotumor), infection (particularly aspergillosis and mucormycosis in diabetic or immunosuppressed patients), neoplastic infiltration, and compression from a sphenoid sinus mucocele should be considered. As in cavernous sinus idiopathic inflammation (Tolosa-Hunt syndrome) versus lymphoma, idiopathic orbital inflammatory pseudotumor and lymphoma at the orbital apex are both likely to be steroid responsive, and lymphoma should be considered, especially if disease recurs with corticosteroid taper. Anatomical division of the oculomotor nerve into superior and inferior branches occurs just before this location, and isolated involvement of either branch is not uncommon.

Isolated Oculomotor Nerve Palsy

Isolated oculomotor dysfunction may occur from any lesion along the course of the nerve (Brazis, 2009). A pupil-sparing oculomotor palsy may represent microvascular ischemia to the nerve, especially in older patients with vascular risk factors. The actual location of ischemia may be anywhere along the course of the nerve but is typically peripheral and often considered to be in the cavernous sinus, although it is not visible with neuroimaging. Pain in the ipsilateral brow and eye is present in two-thirds of patients and may be severe (Wilker et al., 2009). Spontaneous resolution over 8 to 12 weeks is typical. A small percentage of such patients will ultimately be found to have an underlying structural lesion, and neuroimaging should be considered (Chou et al., 2004). In the absence of complete spontaneous resolution, neuroimaging is essential.

Elevation of the eyelid or constriction of the pupil during adduction or depression of the eye is suggestive of aberrant regeneration (anomalous axon innervation). When aberrant regeneration develops following an acute oculomotor palsy, a PCOM artery aneurysm or traumatic etiology is highly probable (see Fig. 70.2, B). When it develops spontaneously without a preexisting acute palsy, a cavernous sinus meningioma or internal carotid artery aneurysm is likely, although this may rarely occur with an unruptured PCOM aneurysm (Carrasco et al., 2002). Aberrant regeneration should not occur following a microvascular oculomotor palsy.

Trochlear Nucleus and Fascicle

It is difficult to differentiate a trochlear nuclear lesion from a fascicular lesion because of the short course of the trochlear fascicle in the brainstem and the predecussation location of both structures. Both locations will result in paresis of the contralateral superior oblique muscle. Isolated nuclear or fascicular involvement occurs rarely; other brainstem signs are usually present (Thomke and Hopf, 2000). Brainstem lesions include ischemia, hemorrhage, demyelination, infectious and noninfectious inflammation, and neoplasm (Jacobson et al., 1999).

Trochlear Palsy Appearance

Trochlear nerve dysfunction results in elevation of the affected eye (hypertropia) and vertical diplopia. The diplopia and hypertropia are worse with downgaze when the eye is in an adducted position, as this is the direction of action of the superior oblique muscle. Impaired depression of the affected eye in the adducted position may be seen but is often subtle (Fig. 70.3). A resting head tilt in the direction away from the paretic eye (e.g., right trochlear palsy, left head tilt) may be present and is considered a sign of chronicity. Because the superior oblique is an intortor of the eye, diplopia is minimized when a contralateral head tilt places the affected eye in an extorted position. Congenital trochlear palsy is relatively common, and identification of a long-standing head tilt in old photographs of the patient can help confirm this diagnosis.

Fig. 70.3 Right trochlear palsy from a large right petroclival meningioma. Patient also had decreased hearing in right ear and cerebellar truncal ataxia. A, Note impaired depression of right eye in adducted position. B, Preoperative T1-weighted coronal magnetic resonance imaging with gadolinium reveals an extensive mass in the pontine cistern, with significant brainstem compression.

Evaluation for superior oblique paresis in the setting of oculomotor nerve dysfunction with impaired adduction from medial rectus paresis is best assessed with the affected eye in an abducted position, where intact intorsion during downgaze suggests intact trochlear function.

Subarachnoid Space

At the point of trochlear nerve decussation, the nerves are near the tentorium cerebelli and are prone to unilateral or bilateral traumatic injury (Keane, 2005). Unlike traumatic oculomotor neuropathy, which usually occurs following severe head trauma with loss of consciousness, the trochlear nerves are injured more easily by minor degrees of head trauma (Dhaliwal et al., 2006).

Trochlear nerve involvement in isolation or accompanied by signs of meningeal inflammation (e.g., meningismus, additional cranial nerve palsies) may occur secondary to inflammatory or neoplastic meningitis. Enhancement of the nerve as it travels dorsally to ventrally around the midbrain may be present on MRI. An increasingly recognized cause of such enhancement in the setting of normal cerebrospinal fluid is trochlear nerve schwannoma (Elmalem et al., 2009; Feinberg and Newman, 1999) (Fig. 70.4).

Fig. 70.4 T1-weighted axial magnetic resonance imaging with gadolinium at level of inferior colliculus shows enhancing lesion consistent with a schwannoma (arrow) on right trochlear nerve as it courses ventrally around brainstem.

Cavernous Sinus

Trochlear palsy in this location is generally accompanied by dysfunction of other structures including the abducens and oculomotor nerves, the first and second divisions of the trigeminal nerve, and sympathetic fibers. Idiopathic inflammation, inflammation from systemic rheumatological disease, metastatic or nasopharyngeal neoplastic infiltration, carotid-cavernous fistulas, and compression from an intracavernous internal artery aneurysm or meningioma are common causes. Pituitary apoplexy very rarely results in isolated trochlear paresis (Petermann and Newman, 1999).

Orbital Apex

Trochlear dysfunction in this location is typically accompanied by dysfunction of neighboring structures including the abducens and oculomotor nerves, the first division of the trigeminal nerve, and the optic nerve. Features of orbital disease such as proptosis, chemosis, and conjunctival injection may be present. Inflammation, infection (particularly aspergillosis and mucormycosis in diabetic or immunosuppressed patients), neoplastic infiltration, and compression from a sphenoid sinus mucocele should be considered.

Trigeminal Nucleus

The extension of the trigeminal nuclear complex throughout the entire brainstem renders it susceptible to involvement from any pathological brainstem process. Trigeminal lesions are particularly common with demyelinating disease, may involve either the nuclei or sensory root, and may be clinically silent or symptomatic (Mills et al., 2010). Ischemia, hemorrhage, infectious and noninfectious inflammation, and neoplasm are other causes of trigeminal brainstem involvement. Additional brainstem signs are frequently present. Wallenberg syndrome from lateral medullary ischemia typically causes ipsilateral facial numbness and impaired pinprick sensation secondary to descending spinal tract and nucleus involvement (see Table 70.1).

Sensory and Motor Roots: Trigeminal Neuralgia

Classic trigeminal neuralgia is characterized by seconds-long stereotyped episodes of intensely painful electric-like shocks along one or more of the trigeminal nerve branches. Pain is often elicited by sensory stimuli on the face, such as shaving or wind. There is no accompanying sensory loss in the affected distribution on examination. The second and third branches are most commonly affected, with less than 5% of patients experiencing involvement of the ophthalmic division. Many cases are attributable to compression of the sensory nerve root by a vascular structure, most often the superior cerebellar artery, and are amenable to surgical decompression (Lorenzoni et al., 2009