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). Because vascular contact with the sensory or motor nerve roots is a relatively common finding in cadavers and asymptomatic controls, vascular contact alone may be insufficient to cause trigeminal neuralgia (Masur et al., 1995; Yousry et al., 2004). Compression or indentation of the nerve root is likely necessary, with resultant axonal loss and demyelination (Miller et al., 2009). See Chapter 69 for additional discussion of trigeminal neuralgia and other facial pain syndromes. Table 70.2, available in the online version of this chapter at www.ExpertConsult.com, outlines current treatments for facial palsy and trigeminal and glossopharyngeal neuralgia.

Table 70.2 Facial Palsy, Trigeminal Neuralgia, and Glossopharyngeal Neuralgia Treatments

Classic trigeminal neuralgia must be differentiated from symptomatic trigeminal neuralgia secondary to an underlying neoplastic, inflammatory, or meningitic cause, with which the pain characteristics may be clinically indistinguishable. It must also be carefully differentiated from other causes of trigeminal neuropathy with differing qualitative and temporal pain qualities and sensory deficits on examination. Cerebellopontine angle acoustic schwannomas frequently involve the sensory nerve root, causing ipsilateral facial sensory symptoms accompanied by ipsilateral tinnitus, deafness, and vertigo from vestibulocochlear nerve involvement.

Trigeminal Ganglion: Herpes Zoster Ophthalmicus

Middle cranial fossa malignant infiltration, compressive neoplastic lesions, and autoimmune inflammation are among the most common causes of trigeminal ganglion pathology. The trigeminal ganglion is a location in which the varicella-zoster virus (VZV) often lies latent, sometimes reactivating along the course of the trigeminal ophthalmic branch later in life to cause herpes zoster ophthalmicus. Identification of skin lesions along the side of the nose (Hutchinson sign) corresponding to the nasociliary branch of the ophthalmic division strongly predict subsequent ocular complications (Nithyanandam et al., 2010).

Trigeminal Nerve Branches

Dysfunction of the ophthalmic branch results in numbness or paresthesias in the anterior scalp, forehead, and supraorbital regions, and an abnormal corneal reflex. A lesion of the maxillary branch affects the cheek, lower eyelid, and upper lip. A lesion of the mandibular branch affects the lower lip, chin, and lateral face anterior to the ear. Motor involvement in a trigeminal nerve lesion is often clinically undetectable. Although it is tempting to localize a trigeminal nerve lesion based on symptom distribution, the complex branching pattern and organization of the trigeminal nuclei and ganglion prohibit such simple localization. It is common for lesions proximal to the nerve branches to evoke symptoms in a single trigeminal branch distribution.

Lesions of a single branch may result from inflammation, compression, or neoplasm. Damage to small distal branches may occur after dental interventions. The ophthalmic branch may be involved in Gradenigo syndrome in combination with the abducens and facial nerves from a lesion at the petrous apex, most common clinically as inflammation following otitis media in children (see Table 70.1). Both the ophthalmic and maxillary branches may be affected by a cavernous sinus lesion, in which setting dysfunction of the oculomotor, trochlear, and abducens nerves is often present.

Two particularly ominous clinical scenarios are (1) insidious development of facial numbness or paresthesias in a patient with a history of facial skin malignancy and (2) the “numb chin” or “numb cheek” syndromes. In the first situation, perineural invasion of the trigeminal branches is likely (Chang et al., 2004; Warden et al., 2009). This is most frequently seen with head and neck adenoid cystic carcinoma, squamous cell carcinoma, and melanoma (Boerman et al., 1999). The numb chin syndrome results from involvement of the mental nerve branches of the mandibular division and is most commonly due to focal metastatic nerve infiltration within the mandible, most often from breast, lung, prostate, or hematological malignancies. This syndrome may rarely be the presenting manifestation of malignancy but more often represents recurrence or progression of known disease (Laurencet et al., 2000). The numb cheek syndrome occurs when branches of the maxillary division are involved.

Abducens Nucleus

Because the abducens nucleus contains the interneurons destined to ascend in the contralateral MLF to the contralateral oculomotor medial rectus subnucleus to permit conjugate horizontal gaze, abducens nuclear lesions cause conjugate horizontal gaze palsy toward the side of the lesion (Muri et al., 1996). Rare cases of isolated horizontal gaze palsy are reported (Miller et al., 2002), but accompanying ipsilateral facial palsy with lower motor neuron facial weakness is typically present. Lesions involving both the abducens nucleus and ipsilateral MLF cause the one-and-a-half syndrome, with an ipsilateral conjugate gaze palsy and impaired adduction of the contralateral eye (see Chapter 19). Brainstem lesions include ischemia, hemorrhage, demyelination, infectious and noninfectious inflammation, and neoplasm (Barr et al., 2000). Periventricular necrosis from Wernicke encephalopathy also frequently results in horizontal gaze or abducens palsy from involvement of the abducens nucleus or fascicle, respectively.

Abducens Palsy Appearance

Abducens nerve dysfunction results in impaired ipsilateral abduction of the eye and deviation of the eyes toward one another (esotropia) (Fig. 70.6 and Videos 70.5 and 70.6 [available at www.ExpertConsult.com]). Binocular horizontal diplopia and the esotropia are worse with gaze in the direction of the abduction deficit.

Fig. 70.6 Right microvascular abducens palsy. A, Central position with esotropia (deviation of eyes toward one another). B, Right gaze with impaired abduction of right eye. C, Normal left gaze.

Brainstem Fascicle

The original Foville syndrome was the combination of an ipsilateral abducens palsy, ipsilateral lower motor neuron facial palsy, and contralateral hemiparesis from corticospinal tract involvement (see Table 70.1). It is now more commonly applied to ipsilateral abducens and facial palsies with contralateral ataxia, ipsilateral Horner syndrome, ipsilateral deafness, and ipsilateral loss of taste and facial sensation. Millard-Gubler syndrome is the combination of ipsilateral abducens and facial palsies with contralateral hemiparesis (see Table 70.1). Raymond syndrome is the combination of ipsilateral abducens palsy and contralateral hemiparesis (see Table 70.1). Brainstem lesions include ischemia, hemorrhage, demyelination, infectious and noninfectious inflammation, and neoplasm. Isolated abducens palsy is rarely the presenting manifestation of demyelination or paraneoplastic brainstem encephalitis (Barr et al., 2000; Hammam et al., 2005).

Quantitative assessment of the velocity of abducting saccades via eye movement recordings may help differentiate a central fascicular abducens lesion from a peripheral abducens palsy. With an acute abducens palsy (<1 month), saccadic velocities are reduced in both fascicular and peripheral lesion locations. However, after 2 months, saccadic velocities return to normal with peripheral lesions and remain impaired with fascicular lesions (Wong et al., 2006).

Subarachnoid Space

An abducens palsy may occur in isolation or in combination with other cranial nerve palsies from infectious, inflammatory, or neoplastic meningitis. The abducens nerve is in close approximation with the clivus and the basilar and vertebral arteries in this location and may be affected by a neoplastic or inflammatory clivus process or compressed by an aneurysm or dolichoectatic artery (Zhu et al., 2005).

The abducens nerves are particularly prone to dysfunction from alterations in intracranial pressure. Abducens palsies may be seen with spontaneous or post–lumbar puncture intracranial hypotension and with intracranial hypertension from any cause, the latter often accompanied by papilledema. It has been suggested historically that the abducens nerve is prone to such injury because of its long intracranial course; however, it has a shorter course than the trochlear nerve, which is the longest intracranial nerve and not prone to injury from raised intracranial pressure. Rather, it is probably the tethered nature of the abducens nerve at the pontomedullary sulcus and at the point of entry into the Dorello canal that predisposes the abducens subarachnoid portion to stretch and distortion injury with alterations in intracranial pressure (Hanson et al., 2004).

Dorello Canal

Abducens palsy is common in Gradenigo syndrome in combination with trigeminal ophthalmic division and facial nerve involvement from a lesion at the petrous apex (see Table 70.1). This is most commonly seen clinically as inflammation following otitis media in children.

Cavernous Sinus

An abducens palsy in this location may occur in isolation or accompanied by dysfunction of the oculomotor and trochlear nerves, the first and second divisions of the trigeminal nerve, and sympathetic fibers. The combination of an abducens palsy and ipsilateral Horner syndrome is highly suggestive of an ipsilateral cavernous sinus lesion, because the sympathetic fibers join the abducens nerve briefly in the posterior cavernous sinus (Tsuda et al., 2005). Inflammation, neoplasms, carotid-cavernous fistulas, and compression from an intracavernous internal carotid artery aneurysm or meningioma may occur.

Orbital Apex

Abducens dysfunction is typically accompanied by dysfunction of neighboring structures including the trochlear and oculomotor nerves, the first division of the trigeminal nerve, and the optic nerve. 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.

Isolated Abducens Palsy

An isolated painful abducens palsy may represent microvascular ischemia, especially in older patients with vascular risk factors (Brazis, 2009) (see Fig. 70.6). Spontaneous resolution over 8 to 12 weeks is typical. In the absence of complete spontaneous resolution, neuroimaging is essential (Chi and Bhatti, 2009). Head trauma, even if mild, is another relatively common cause of abducens palsy (Dhaliwal et al., 2006). Impaired ability to abduct the eye past midline or bilateral presentation predict poor spontaneous recovery (Holmes et al., 2001). The abducens nerve is the cranial nerve most commonly affected bilaterally in isolation. This occurs most often from trauma and increased intracranial pressure (Keane, 2005).

Facial Palsy Appearance

Facial nerve dysfunction results in unilateral upper and lower facial weakness manifested by flattening of the nasolabial fold, an asymmetrical smile, poor eyebrow elevation, decreased forehead wrinkling, and weak eye closure (Fig. 70.8 and Video 70.7 [available at www.ExpertConsult.com]). The palpebral fissure is widened on the affected side, and deviation of the eye upward and laterally with attempted eye closure (Bell phenomenon) may become visible because of orbicularis oculi weakness. Attention to adequacy of corneal coverage with provision of appropriate lubrication and protection will minimize the risk for permanent corneal damage from exposure due to incomplete eye closure. Lesions proximal to the greater superficial petrosal nerve increase the risk for corneal damage by impairing lacrimal secretion (for treatments, see Table 70.2, available in the online version of this chapter at www.ExpertConsult.com).

Fig. 70.8 Left facial palsy with widened left palpebral fissure and left facial droop. Patient had a prior history of right facial palsy.

Although it is theoretically possible to localize the facial nerve lesion to a specific nerve portion with specialized tests of tear production, stapedial muscle reflex, salivation, and taste, the primary clinical manifestation of facial nerve dysfunction is facial weakness. This must be distinguished from upper motor neuron facial weakness that causes only lower facial weakness because of the bilateral supranuclear innervation to the upper facial muscles, which may originate from upper facial cortical motor representation outside the primary motor cortex in the cingulate gyrus (Morecraft et al., 2001). Upper motor neuron facial weakness may also result in selective facial weakness for either volitional or emotional facial movements, whereas lower motor neuron facial weakness from facial nerve palsy affects both equally.

Facial Nucleus and Fascicle

Although isolated lower motor neuron weakness occasionally occurs from a brainstem lesion, accompanying brainstem signs, such as horizontal gaze palsy from sixth nerve nuclear involvement, are typically present. The original Foville syndrome was the combination of an ipsilateral abducens palsy, ipsilateral lower motor neuron facial palsy, and contralateral hemiparesis from corticospinal tract involvement (see Table 70.1). It is now more commonly applied to ipsilateral abducens and facial palsies with contralateral ataxia, ipsilateral Horner syndrome, ipsilateral deafness, and ipsilateral loss of taste and facial sensation. Millard-Gubler syndrome is the combination of ipsilateral abducens and facial palsies with contralateral hemiparesis (see Table 70.1). Brainstem lesions include ischemia, hemorrhage, demyelination, infectious and noninfectious inflammation, and neoplasm. Continuous twitching of individual facial muscles, called facial myokymia, is most commonly seen with demyelination and brainstem gliomas.

Nerve Root: Hemifacial Spasm

Hemifacial spasm (HFS) is characterized by involuntary episodic contractions of the muscles innervated by the facial nerve (see Video 70.7, available at www.ExpertConsult.com). It is most often unilateral and may be caused by compression and indentation of the facial motor nerve root at its brainstem exit by an aberrant vascular loop or dolichoectatic artery (Ho et al., 1999). HFS infrequently results from neoplastic compression or inflammation of the nerve root or from intrapontine lesions such as tumor or demyelination (Han et al., 2009). Facial weakness in isolation or in combination with other cranial nerve palsies may result from infectious, inflammatory, or neoplastic meningitis. Cerebellopontine angle mass lesions such as meningioma or acoustic schwannoma may cause facial nerve involvement. The facial nerve and vestibulocochlear nerves form a complex as they exit the brainstem, and sensorineural hearing loss is nearly always the primary feature of acoustic schwannomas. Acoustic schwannomas may be difficult to differentiate from facial nerve schwannomas in the cerebellopontine angle, but the latter tend to have earlier clinical facial weakness and the radiological appearance of a “labyrinthine tail” as the facial schwannoma extends into the facial canal in the temporal bone (Marzo et al., 2009; Wiggins et al., 2006).

Intratemporal Facial Nerve and Geniculate Ganglion: Bell Palsy

Bell palsy is a self-limited, typically monophasic facial nerve palsy of acute-subacute onset (see Fig. 70.8 and Table 70.1). Pain accompanies facial weakness in 60% of patients, impaired lacrimation in 60%, taste changes in 30% to 50%, and hyperacusis in 15% to 30%. Ipsilateral facial sensory symptoms are not uncommon and are hypothetically explained by extension of inflammation from the facial nerve to the trigeminal nerve via the greater superficial petrosal nerve (Vanopdenbosch et al., 2005). Internal auditory canal MRI often reveals enhancement of the facial nerve, most commonly at the geniculate ganglion. Eighty-five percent of patients spontaneously recover normal facial function in 3 weeks (Peitersen, 2002). Bell palsy occurs with increased frequency during pregnancy, in which setting it is associated with a poorer recovery rate (Gillman et al., 2002). Residual abnormalities after acute Bell palsy occur in 12% of patients and include persistent severe facial weakness in 4% and synkinetic contraction and twitching of the upper and lower facial muscles in 17% (Beurskens et al., 2010; Kanaya et al., 2009) (see Video 70.7, available at www.ExpertConsult.com). Acutely, the nasolabial fold is flattened and the palpebral fissure is widened on the affected side; however, with chronicity, the affected side often becomes hypercontracted, with a deepened and prominent nasolabial fold and a narrowed palpebral fissure. Aberrant regeneration involving the lacrimal gland may result in tearing with facial muscle contraction (syndrome of “crocodile tears”), particularly during eating. Electromyographic presence of spontaneous fibrillation in facial muscles 10 to 14 days after onset of facial weakness is predictive of poor outcome (Sittel and Stennert, 2001). Bell palsy may be recurrent, but alternative causes such as Lyme disease or sarcoidosis must be considered. Bilateral facial weakness is also common with acute inflammatory demyelinating polyneuropathy, Lyme disease, sarcoidosis, and Epstein-Barr virus infection (Coddington et al., 2010; Morris et al., 2002).

Although Bell palsy is considered idiopathic, herpes simplex virus and VZV reactivation in the geniculate ganglion have been implicated in its pathogenesis. High-quality evidence of treatment effect was lacking until recently, but early administration of corticosteroids and antiviral agents was common practice. Evidence now demonstrates a clear benefit in preventing unsatisfactory recovery for oral corticosteroids alone. Treatment with antiviral agents alone is not associated with a reduced risk of unsatisfactory recovery, although co-administration of corticosteroids and antiviral agents may provide added benefit over corticosteroids alone (Almeida et al., 2009; Thaera et al., 2010).

Ramsay Hunt syndrome consists of facial nerve palsy accompanied by a vesicular otic or oral rash due to VZV, with or without vestibulocochlear symptoms (see Table 70.1). The vesicular outbreak may occur before, after, or simultaneously with the facial weakness. Diagnosis is confirmed by a rise in serological VZV titers or positive VZV polymerase chain reaction (PCR). Serological detection or positive VZV PCR in facial palsy without a vesicular rash suggests zoster sine herpete. Facial weakness is more severe and spontaneous recovery less common in Ramsey Hunt and zoster sine herpete compared to idiopathic Bell palsy. Early diagnosis and initiation of corticosteroid and antiviral treatment significantly improves recovery (Furuta et al., 2000; Murakami et al., 1997).

Intratemporal facial nerve schwannomas within the facial canal, traumatic fractures and occult skull-based neoplasms of the temporal bone, and complicated otitis media with mastoiditis may also affect the facial nerve and should be considered when the onset of facial weakness is insidious and the course is progressive and accompanied by hearing loss (i.e., because of the proximity of the vestibulocochlear nerve). Gradenigo syndrome results from inflammation of the petrous apex and causes facial nerve palsy in combination with trigeminal and abducens nerve impairment (see Table 70.1). Traumatic temporal bone fractures may cause immediate or delayed facial nerve palsy (Nash et al., 2010).

Facial Nerve Branches

Parotid neoplasms, surgical procedures, and infiltration of facial skin cancers along facial motor nerve branches may result in weakness of individual facial nerve innervated muscles. Taste changes and hyperacusis do not typically occur with these lesions, given their distal nature, and either the upper or lower facial muscles may be affected in isolation. This may lead to diagnostic confusion with an upper motor neuron lesion when only the lower facial musculature is involved. Peripheral branches may also be affected by Lyme disease and sarcoidosis in the absence of meningeal inflammation. Melkersson-Rosenthal syndrome is a rare granulomatous disease with a triad of facial nerve palsy, facial edema, and tongue fissures (see Table 70.1). The complete triad occurs in only a quarter of patients.

Glossopharyngeal Palsy Appearance

Glossopharyngeal dysfunction results in loss of the gag reflex ipsilateral to the lesion and poor pharyngeal elevation with speaking and swallowing, which appears clinically as dysarthria and dysphagia. Taste in the posterior tongue may be impaired, and patients may complain of a dry mouth from decreased salivary secretory functions.

Nerve Root: Glossopharyngeal Neuralgia

Glossopharyngeal neuralgia is characterized by paroxysmal severe episodes of unilateral stabbing pain in the tongue base, tonsilar fossa, pharynx, or middle ear. It is often triggered by oropharyngeal movements such as chewing, swallowing, or yawning. It may very rarely be associated with syncope when vascular compression of the glossopharyngeal and vagus nerve roots together result in dysfunction of the glossopharyngeal-vagal reflex arc, with precipitation of bradycardia or asystole (Takaya et al., 2003). Glossopharyngeal neuralgia is much less common than trigeminal neuralgia, but like trigeminal neuralgia, neurovascular compression of the nerve root is likely a common etiology, and surgical neurovascular decompression may result in symptom relief (see Chapter 69) (Spengos et al., 2005) (for treatments, see Table 70.2, available at www.ExpertConsult.com).

Compressive lesions of the nerve root (e.g., cerebellopontine angle neoplasms, Chiari I malformations) may also cause glossopharyngeal neuralgia. Brainstem pathology such as tumor and demyelination is an infrequent cause (Minagar and Sheremata, 2000). Eagle syndrome from compression of the glossopharyngeal nerve by an elongated styloid process or ossified stylohyoid ligament may mimic glossopharyngeal neuralgia, but the pain tends to be more persistent and dull in nature (Mendelsohn et al., 2006; Piagkou et al., 2009) (see Table 70.1).

Petrosal Ganglion and Jugular Foramen

Neoplasia, blunt and penetrating trauma, inflammation, and internal carotid artery dissections may affect glossopharyngeal function at the jugular foramen. Vernet syndrome is a pure jugular foramen syndrome with involvement of the glossopharyngeal, vagus, and spinal accessory nerves (see Table 70.1). Since the jugular foramen is in close proximity to the hypoglossal canal that houses the hypoglossal nerve, simultaneous involvement of cranial nerves IX through XII is not uncommon. When accompanied by Horner syndrome from sympathetic involvement, the combination is called Villaret syndrome (posterior retropharyngeal) and is most commonly due to internal carotid artery dissection or neoplasm (see Table 70.1). In the absence of Horner syndrome, the combination is called Collet-Sicard syndrome (see Table 70.1), which may occur with carotid dissection, neoplasm, inflammation, or trauma (Rees et al., 1997).

Glomus jugulare tumors of the jugular bulb are the most common tumors in the jugular foramen (Fayad et al., 2010). They are slow-growing, hypervascular, benign paragangliomas that present with a neck mass, pulsatile tinnitus, lower cranial nerve dysfunction, and hearing loss from extension into the middle ear (Karaman et al., 2009). Examination of the lower cranial nerves reveals the deficits to be strictly unilateral, and skull-base imaging will reveal the lesion. Glomus tumors may also occur in the middle ear tympanic plexus, on the vagus nerve, and in the carotid body. Schwannomas, meningiomas, and metastases also occur in the jugular foramen. Glossopharyngeal schwannomas more often present with vestibulocochlear dysfunction than glossopharyngeal involvement (Vorasubin et al., 2009).

Glossopharyngeal Nerve Branches

Direct pressure or stretch injury of the branches may occur from surgical intervention, particularly with suspension laryngoscopy and tonsillectomy (Ford and Cruz, 2004). Postoperative taste changes and impaired swallowing are usually transient (Rosen et al., 2005). Reflex otalgia, or referred middle ear pain, occurs with oropharyngeal neoplasms owing to the anatomical neural connections between the oropharyngeal and tympanic branches. It is generally a poor prognostic sign that increases the likelihood of tumor recurrence after treatment (Thoeny et al., 2004). Syncope in a patient with a history of head and neck cancer may be an ominous harbinger of recurrent disease (Nakahira et al., 2002). Carotid hypersensitivity syndrome (syncope provoked by carotid massage), glossopharyngeal neuralgia with syncope, and parapharyngeal space-lesion syncope syndrome (syncope in the absence of neuralgia or carotid massage) are all occasionally seen from focal neoplastic infiltration of the glossopharyngeal nerve and the glossopharyngeal-vagal reflex arc.

Vagus Palsy Appearance

Vagus dysfunction results in unilateral loss of pharyngeal and laryngeal sensation, unilateral loss of sensation in the external ear, dysphagia, hoarseness of the voice, unilateral paralysis of the uvula and soft palate, and deviation of the uvula contralateral to the lesion. Otolaryngological examination reveals unilateral paralysis of the vocal cords.

Vagus Nucleus

Nuclear lesions may result from ischemia, hemorrhage, infectious and noninfectious inflammation, neoplasm, and demyelination. Wallenberg syndrome from lateral medullary ischemia affects the nucleus ambiguus, causing dysphagia with bilateral impairment of pharyngeal and laryngeal function, likely explained by involvement of bilateral cortical prenuclear inputs into each nucleus (Aydogdu et al., 2001) (see Table 70.1). Swallowing impairment is accompanied by hoarseness of the voice, decreased gag reflex, facial pain from trigeminal involvement, limb ataxia from cerebellar peduncle involvement, Horner syndrome, contralateral body impaired pain and temperature sensation from spinothalamic tract involvement, and vertigo from vestibular involvement. Opalski syndrome is a variant of the lateral medullary syndrome accompanied by ipsilateral hemiparesis due to extension of the lesion into the cervical spinal cord, affecting corticospinal fibers caudal to the pyramidal decussation. Ipsilateral palatolaryngeal paresis in combination with contralateral hemiparesis (Avellis syndrome) occurs most commonly from medullary pathology, although the initial description of the syndrome was secondary to extramedullary vagus nerve involvement, presumably from a large lesion causing ventral brainstem compression with hemiparesis (Krasnianski et al., 2003) (see Table 70.1). Nuclear involvement in multisystem atrophy and Lewy body disease may explain the cardiovagal failure and gastrointestinal symptoms in these diseases (Benarroch et al., 2006). Motor neurons in the nucleus ambiguus are preferentially affected in amyotrophic lateral sclerosis.

Nodose Ganglion and Jugular Foramen

Neoplasm, blunt and penetrating trauma, inflammation, and internal carotid artery dissection may affect vagus function at the jugular foramen. Vernet syndrome is a pure jugular foramen syndrome with involvement of the glossopharyngeal, vagus, and spinal accessory nerves (see Table 70.1). Simultaneous involvement of cranial nerves IX through XII is common because of the proximity of the jugular foramen and hypoglossal canal. As noted earlier, when accompanied by Horner syndrome, the combination is called Villaret syndrome (posterior retropharyngeal) (Rees et al., 1997); in the absence of Horner syndrome, the combination is called Collet-Sicard syndrome; and the combination of vagus and hypoglossal nerve lesions is called Tapia syndrome (see Table 70.1), although the original description was of a patient with a brainstem lesion and contralateral hemiparesis.

Glomus jugulare tumors of the jugular bulb were described earlier in this chapter in the section on Glossopharyngeal Nerve (Cranial Nerve IX), Petrosal Ganglion and Jugular Foramen.

Vagus Nerve Branches

Direct pressure or stretch injury of the branches may occur from surgical intervention, particularly recurrent laryngeal nerve injury with thyroid or esophageal surgery, or vagus nerve stimulator placement for treatment of epilepsy or refractory depression. Peripheral branches may be affected by herpes zoster, paragangliomas, thoracic lymphadenopathy, and neoplasms. Referred ear pain may occur with chest neoplasms, owing to direct infiltration or compression of nerve branches connected via the trigeminal nuclear system to sensory vagus nerve branches to the ear.

Spinal Accessory Palsy Appearance

Spinal accessory nerve dysfunction results in weakness of contralateral head turning and ipsilateral shoulder elevation. Unilateral atrophy of the sternocleidomastoid and trapezius occurs with chronic lesions (Fig. 70.10). Scapular winging with active external shoulder rotation may be seen (Chan and Hems, 2006). Pain in the neck or shoulder is common.

Fig. 70.10 A, Normal left sternocleidomastoid muscle with forceful thrust of chin to the right. Note prominent left sternocleidomastoid muscle. B, Same maneuver shown in A but to the left, showing loss of bulk of right sternocleidomastoid muscle.

Spinal Accessory Nucleus

Amyotrophic lateral sclerosis preferentially involves the spinal accessory and other motor neurons in the ventral horns of the spinal cord. Intrinsic spinal cord pathology such as neoplasm or syrinx may affect these motor neurons in combination with other spinal tracts.

Jugular Foramen

Vernet, Villaret, and Collet-Sicard syndromes are described earlier and in Table 70.1.

Spinal Accessory Nerve Branches

Iatrogenic injury during lymph node biopsy or dissection for head and neck cancers is the most common cause of spinal accessory nerve dysfunction. Variations in individual branch anatomy make the nerve particularly prone to difficult identification and traction or ischemic injury. Involvement of the dominant arm, scapular winging, and limited arm elevation are poor prognostic indicators (Friedenberg et al., 2002). Spinal accessory branches may be intentionally injured in treatment for cervical dystonia. Trauma and isolated peripheral neoplasms occur rarely.

Hypoglossal Palsy Appearance

Hypoglossal nerve dysfunction results in atrophy and fasciculation of the ipsilateral tongue muscles and ipsilateral deviation of the tongue upon protrusion from the mouth (Fig. 70.12).

Fig. 70.12 Axial computed tomography scan through tongue in patient with right hypoglossal palsy. Note tongue atrophy on right side (black arrow).

(Courtesy Miral Jhaveri, MD.)

Hypoglossal Nucleus and Fasciculus

The medial medullary syndrome of Dejerine consists of ipsilateral tongue weakness, contralateral hemiplegia from pyramidal tract involvement, and contralateral hemisensory loss from medial lemniscal involvement (see Table 70.1) (Bassetti et al., 1997). More common than isolated medial medullary syndrome is the hemi-medullary syndrome of Babinski-Nageotte that combines Dejerine and Wallenberg syndromes: swallowing impairment, hoarseness of the voice, decreased gag reflex, facial pain, limb ataxia, Horner syndrome, contralateral hemibody impaired pain and temperature sensation, and vertigo (see Table 70.1). As with the other cranial nerves, there are multiple etiologies, including amyotrophic lateral sclerosis. Although neurovascular compression as the hypoglossal nerve roots exit the brainstem is not classically considered a cause of hypoglossal palsy, recently reported cases suggest this as a diagnostic possibility (Osburn et al., 2010; Straube and Linn, 2008).

Hypoglossal Canal

Neoplasm, blunt and penetrating trauma with occipital condyle fractures, inflammation, and postradiation injury may affect hypoglossal function at the hypoglossal canal. Since the hypoglossal canal is in close proximity to the jugular foramen, simultaneous involvement of cranial nerves IX through XII is not uncommon. Villaret, Collet-Sicard, and Tapia syndromes are described earlier and in Table 70.1.

Hypoglossal Peripheral Branches

Mechanisms of hypoglossal branch disease are similar to those in the hypoglossal canal. Hypoglossal dysfunction is an ominous clinical finding; 50% of cases are caused by neoplasm, typically malignant (Keane, 1996). Nasopharyngeal carcinoma and skull-based metastatic disease are among the most common malignancies affecting the hypoglossal nerve. The combination of hypoglossal dysfunction with an abducens palsy is highly suggestive of an aggressive clival malignancy (Keane, 2000). Retropharyngeal mass lesions other than malignancy include granulomatous inflammation and abscess. Hypoglossal palsy may be the presenting manifestation of carotid artery dissection or aneurysm and may occur iatrogenically after carotid endarterectomy, occasionally disclosing underlying hereditary neuropathy with liability to pressure palsy (Corwin and Girardet, 2003; Mokri et al., 1996).