ABDUCENS NERVE:CRANIAL NERVE VI
Signs and symptoms
Anatomy: clinical implications
Differential diagnosis and evaluation
TROCHLEAR NERVE: CRANIAL NERVE IV
Signs and symptoms
Anatomy: clinical implications
Evaluation and management
OCULOMOTOR NERVE:CRANIAL NERVE III
Signs and symptoms
Anatomy: clinical implications
Evaluation and management
MULTIPLE CRANIAL NEUROPATHIES
Anatomy: clinical implications
Evaluation and differential diagnosis
Cranial nerves (CNs) III (oculomotor), IV (trochlear), and VI (abducens) provide motor input to the extraocular muscles. The oculomotor nerve also innervates the levator of the upper eyelid and provides parasympathetic input to the pupillary sphincter. Disorders involving these cranial nerves can cause ocular misalignment and diplopia. Oculomotor palsies can also cause ptosis and anisocoria.
An overview of cranial nerve anatomy is provided in Figure 9–1. The three ocular motor cranial nerves originate as brainstem motor nuclei. The motor nuclei receive input from various supranuclear sources to coordinate movement of the eyes. Motor axons traverse the brainstem as fascicles, often passing through or near structures that can be simultaneously involved with brainstem disease. The axons then exit the brainstem, forming a peripheral cranial nerve, passing through the subarachnoid space and cavernous sinus to innervate the extraocular muscles. The cranial nerves can be affected by many disease processes along their course (Table 9–1). Neighboring structures along the course of each of the cranial nerves may be involved in cranial neuropathies, producing distinctive signs and symptoms that frequently allow localization and characterization of a lesion.
(A) The nuclei and course of cranial nerves (CNs) III, IV, and VI are shown. CN IV is the only cranial nerve to exit the dorsal brainstem. All three ocular motor nerves travel through the cavernous sinus to enter the orbit. (B) Cavernous sinus (coronal view). CNs III and IV travel in the lateral wall of the sinus, but CN VI occupies a more vulnerable mid-cavernous route. The first (ophthalmic) branch of the trigeminal nerve (V1) traverses the length of the sinus to enter the orbit through the superior orbital fissure; the second (maxillary) branch (V2) exits mid-cavernous sinus; and the third (mandibular) branch (V3) may variably have a brief appearance in the posterior cavernous sinus (not pictured).
CAUSES BY LOCATION OF OCULAR MOTOR CRANIAL NEUROPATHIES (CN III, IV, VI)
|Brainstem (nuclei and fascicles)
|MS, postviral, Miller Fisher variant of Guillain-Barré syndrome
|Stroke, hemorrhage, microvascular disease, dolichoectatic basilar arterie, arteriovenous malformation
|Toxoplasma gondii, abscess
|Infection (basilar meningitis)
|Tuberculosis, cryptococcosis, AIDS, syphilis, and occasionally bacterial infections
|Clivus chordoma, meningioma, carcinomatous meningitis, leukemia, subarachnoid metastasis from ependymomas, medulloblastoma, CNS lymphoma, other neoplasms
|Invasive extracranial neoplasms
|Adenoid cystic carcinoma, nasopharyngeal carcinoma
|Uncertain: subarachnoid space or cavernous sinus
|Microvascular (ischemic mononeuropathy)
|Diabetes, hypertension, collagen vascular disease, giant cell arteritis, atherosclerosis
|Cavernous sinus/superior orbital fissure
|Septic thrombosis Parasellar tumors
|Bacterial infection, mucormycosis, Aspergillus Meningioma, craniopharyngioma, pituitary adenoma, pituitary apoplexy, chordoma, neurilemmoma
|Myeloma, lymphoma, metastasis (breast, lung), tumor extension from paranasal sinus, bone tumors
|Carotid-cavernous fistula, intracavernous aneurysm
|Cavernous sinus, superior orbital fissure, or orbital apex
|Tolosa-Hunt syndrome, sarcoidosis, herpes zoster
|Idiopathic orbital inflammatory syndrome
|Variable or unknown location
ABDUCENS NERVE: CRANIAL NERVE VI
The abducens nerve (CN VI) innervates the lateral rectus muscle in the ipsilateral orbit. As its name describes, this cranial nerve is responsible for abduction of the eye, and paresis causes an abduction deficit.
Patients with a CN VI palsy describe horizontal diplopia, worse in gaze toward the palsied muscle. Diplopia may not be a problem at near because convergence moves the eye away from the field of action of the lateral rectus muscle; in other words, the lateral rectus is inhibited with convergence anyway, so a weak lateral rectus is not as likely to cause symptoms with near tasks such as reading.
The measured esotropia in CN VI disorders is incomitant and is much greater in the field of action of the palsied muscle (Figure 9–2). Patients may adopt a head turn posture, with the face turned toward the palsied eye, to minimize the strabismus. A small vertical deviation is often present with lateral rectus weakness, which should not be mistaken for a superimposed skew deviation.
Disorders that can affect CN VI, and the occurrence of associated neurological signs and symptoms, are a direct consequence of the local neuroanatomy.
The paired abducens nuclei are located in the brainstem at the level of the pons and fourth ventricle (Figure 9–3A). The nucleus contains two types of neurons: motor neurons whose axons form the ipsilateral sixth cranial fascicle and nerve, and internuclear neurons. The internuclear neurons send their axons across the midline to ascend in the contralateral medial longitudinal fasciculus (MLF), where they synapse with neurons in the contralateral medial rectus subnucleus to coordinate conjugate horizontal gaze (see Figure 10–2). Therefore, CN VI nuclear lesions produce an ipsilateral gaze palsy, not just an abduction defect. Involvement of the adjacent paramedian pontine reticular formation (PPRF) and MLF can result in a gaze palsies or a one-and-a-half syndrome (see Figure 10–6). The facial nerve (CN VII) nucleus lies ventrally with fascicles that loop superiorly over the abducens nucleus, forming a bump on the floor of the fourth ventricle (the facial colliculus). This anatomic landmark is useful in identifying the level of the abducens nucleus on axial magnetic resonance imaging (MRI) scans. Disorders affecting the abducens nucleus include brainstem gliomas, metastatic lesions, infarctions, and arteriovenous malformations.
Cranial nerve VI anatomy.
(A) Brainstem cross section at the level of the cranial nerve (CN) VI nucleus. Neighboring structures and associated signs and symptoms are identified. (B) Subarachnoid course. CN VI exits the brainstem at the pontomedullary junction into the subarachnoid space and climbs up the clivus, piercing the dura and turning toward the cavernous sinus under the petroclinoid ligament through Dorello canal.
Motor fascicles from the abducens nucleus travel ventrally through the pontine tegmentum toward the pontomedullary junction. Lesions that involve the CN VI fascicles frequently also affect adjacent pontine structures, including the facial nerve nucleus and fascicles, descending oculosympathetic fibers, trigeminal nucleus and fascicles, corticospinal tract, and others. Millard-Gubler syndrome is a CN VI paresis with an ipsilateral CN VII palsy and contralateral hemiparesis, implicating a ventral pontine lesion. Raymond syndrome is a CN VI paresis with contralateral hemiparesis. Foville syndrome occurs from a dorsal pontine lesion and consists of ipsilateral CN V, VII, and VIII palsies, with a horizontal gaze palsy and an ipsilateral Horner syndrome (see Figure 9–3A).
Infarction from vascular disease is the most common lesion involving the abducens fascicles in patients older than 50 years; demyelination from multiple sclerosis (MS) and brainstem gliomas can occur in younger patients. Cerebellar tumors can affect the abducens nucleus or fascicles by compression or extension into the pons.
CN VI exits the brainstem at the pontomedullary junction approximately 1 cm from the midline, entering the subarachnoid space within the cerebellopontine angle. This anatomic space is bounded by the cerebellum and brainstem and includes CN VII and CN VIII. Mass lesions in this area that involve CN VI frequently also affect the neighboring structures, resulting in a CN VI palsy, facial palsy, and hearing loss, frequently with papilledema (see Figure 9–3B). Acoustic neuromas, meningiomas, cerebellar tumors, and nasopharyngeal carcinoma can occur in the cerebellopontine angle.
After exiting the brainstem and traversing the subarachnoid space, CN VI ascends in close association with the dura of the clivus. Metastatic tumors to the clivus (especially prostate), meningiomas, and clivus chordomas can affect CN VI unilaterally or bilaterally in this region. As the nerve ascends toward the top of the clivus, it turns to follow a more level course and enters Dorello canal, passing beneath the petroclinoid (Gruber) ligament and over the petrous apex to enter the cavernous sinus. Because the inferior petrosal sinus also shares this confined space, CN VI palsies frequently accompany the venous engorgement that occurs with carotid-cavernous sinus fistulas or cavernous sinus thrombosis.
The subarachnoid portion of CN VI is firmly attached at the pontomedullary junction of the brainstem inferiorly and at Dorello canal in the skull base superiorly. Because of these tether points, the nerve is vulnerable to stretching injury from any downward movement of the brain relative to the skull base, as can occur with intracranial hypertension, as a result of lumbar puncture, or in closed head injury.
Gradenigo syndrome consists of severe facial pain and numbness, unilateral CN VI palsy, facial paresis, and decreased hearing, as the result of severe otitis media involving the petrous apex, where CN VI and CN VII are in close proximity. In the modern antibiotic era, otitis media in children rarely manifests this way. In adults, the syndrome complex suggests a cholesteatoma or nasopharyngeal carcinoma.
Basal skull fractures frequently involve the petrous apex and CN VI, also involving the facial nerve when the temporal bone is fractured. Associated signs include cerebrospinal fluid (CSF) otorrhea, blood in the external auditory meatus, and mastoid ecchymosis (Battle sign).
CN VI runs through the middle of the cavernous sinus just lateral to the carotid artery, unlike CN III and CN IV, which travel somewhat protected in the lateral wall of the sinus (see Figure 9–1B). This position of CN VI in the cavernous sinus makes the nerve vulnerable, and it is often the first cranial nerve to be affected by cavernous sinus disease processes, such as intracavernous aneurysms, carotid-cavernous fistulas, metastatic tumors, and laterally invasive sellar tumors. Sympathetic fibers from the carotid plexus condense and travel briefly on the abducens nerve in the cavernous sinus before joining the first division of CN V to enter the orbit. The combination of an oculosympathetic paresis (Horner syndrome) accompaning a CN VI palsy is highly suggestive of a cavernous sinus process.
Infarction of CN VI (ischemic cranial mononeuropathy) is common with diabetes mellitus, presumably occurring in the cavernous sinus. Associated periorbital pain is most likely caused by ischemia of the adjacent meninges. The nerve is capable of regenerating and regrows along its original course, guided by the myelin tunnel left behind after axonal degeneration. Normal function usually returns within 3 months.
CN VI enters the orbit through the superior orbital fissure, inside the annulus of Zinn (and within the muscle cone), and innervates the lateral rectus muscle, entering the muscle on its mesial surface. CN VI, III, and IV can be affected by inflammatory conditions affecting the superior orbital fissure and orbital apex (see Table 9–1).
The sudden onset of an isolated abduction deficit in a patient with known vascular disease or in a patient older than 50 years likely represents an ischemic mononeuropathy. The disease process can occur in younger patients, especially with systemic vascular risk factors such as diabetes mellitus or hypertension. Pain can occur but is usually slight and confined to the first week. Because ischemic cranial mononeuropathies can occur with vasculitis, laboratory evaluation should include a sedimentation rate and C-reactive protein. Patients with no known risk factors for ischemic disease should have a medical evaluation for diabetes mellitus, systemic hypertension, hypercholesterolemia, and atherosclerotic disease. Although recovery usually takes 6 weeks or more, reexamination of the patient in the first 2 to 4 weeks after onset is prudent. This follow-up visit is to ensure that the abduction deficit is not progressing and remains isolated, with no signs to suggest involvement of other cranial nerves (suggesting tumor) or variable signs and symptoms (suggesting myasthenia gravis). Most patients have resolution of diplopia by 3 months; those patients with persistent signs and symptoms beyond this time may need additional investigation (such as neuroimaging) for other possible causes.
Compressive lesions of CN VI are characterized by a progressive worsening of the abduction deficit, often with other associated cranial neuropathies or evolving neurological signs. An MRI is indicated if a CN VI palsy is slowly progressing, if the patient has a history of a brain or sinus tumor or potentially metastatic cancer, if other cranial nerves are involved, if the patient is experiencing unrelenting facial pain, or if other neurological symptoms are present. MRI of the brain with contrast allows a detailed view of the brainstem and the course of the nerve, which is not possible with computed tomography (CT) imaging. MRI of the orbit may need to be included if orbital processes (eg, orbital Graves disease) remain in the differential diagnosis.
Children may develop isolated unilateral or bilateral CN VI palsy as a postviral syndrome, presumably autoimmune in origin, with spontaneous recovery. Because brainstem gliomas and cerebellar tumors are a concern in this age group, neuroimaging and close observation for the development of other neurological signs (gaze palsies, cerebellar signs) are required. An otoscopic examination should be performed to address the possibility of middle ear infections.
Unilateral or bilateral CN VI palsies can occur with elevated intracranial pressure. The importance of examining the optic discs in this setting is obvious—and is a reminder to the physician of the importance of completing all the basic steps in the neuro-ophthalmic examination, even steps (eg, fundus examination) that appear unrelated to the complaint (eg, diplopia).
Divergence insufficiency is a poorly understood disorder consisting of an esotropia at distance and orthophoria at near in a patient with full ductions, usually identified in patients 60 years or older. Whether this disorder represents a microischemic vascular lesion in a divergence center in the brainstem or is a mild bilateral CN VI paresis is uncertain.
Patients with an abduction deficit should not be immediately labeled as having a CN VI paresis (Table 9–2). Restriction of the medial rectus from orbital Graves disease, traumatic medial rectus entrapment, and idiopathic orbital inflammatory syndrome (IOIS) (and other orbital causes) can also cause an abduction deficit. Ocular myasthenia gravis can produce virtually any ocular motility pattern, including an isolated abduction deficit. Congenital esotropia can usually be distinguished from bilateral CN VI palsies because it is comitant and associated with other findings, including latent nystagmus, oblique muscle dysfunction, and amblyopia.
DIFFERENTIAL DIAGNOSIS OF AN ABDUCTION DEFICIT
Convergence spasm can mimic bilateral CN VI palsies (Figure 9–4). When this condition occurs with dorsal midbrain syndrome, other signs are invariably present (see Table 10–1). Convergence spasm can be a component of latent hyperopia or presbyopia. Voluntary convergence (functional convergence spasm) is accompanied by miosis and cannot be sustained indefinitely.
Convergence (accommodative) spasm.
(A) A patient thought to have intermittent cranial nerve VI palsies is shown to have normal horizontal ocular motility by doll’s head maneuver. (B) However, attempts to perform ocular versions resulted in marked esotropia, with a pseudoabduction deficit. Note the miotic pupils, confirming that this is an accommodative/convergence spasm.
Duane syndrome is a congenital condition causing an ocular motility disorder that surprisingly may not be recognized until adulthood. Patients with an incidentally discovered horizontal strabismus may have Duane syndrome, but the physician must be confident that the patient does not have an acquired strabismus before attributing an abduction deficit to Duane syndrome. Duane syndrome is the result of congenital aplasia or hypoplasia of CN VI nucleus and nerve (unilateral, rarely bilateral), often with anomalous innervation of the lateral rectus muscle by CN III. Characteristics include narrowing of the fissure on attempted abduction from cocontraction and dynamic enophthalmos. Patients may have deficient abduction, adduction, or both (Figure 9–5). Amblyopia is rare. Patients may have a head turn to maintain binocularity.
(A) Duane type 1 is characterized by an abduction deficit and narrowing of the fissure on adduction, as seen in the left eye of this child. (B) Duane type 2 (right eye) is demonstrated in this patient’s clinical photographs: an adduction deficit in the right eye, and narrowing of the fissure on attempted adduction of the right eye. Duane type 3 (not shown) has both adduction and abduction deficits.
Möbius syndrome is a congenital malformation that involves multiple brainstem nuclei and results in bilateral abduction or gaze palsies, bilateral hypoglossal paralysis, and bilateral facial palsies (see Figure 12–6).
Treatment of CN VI palsy is determined by the underlying cause. Long-standing palsies that have no potential for spontaneous recovery may benefit from strabismus surgery. Spectacle prisms are occasionally helpful in allowing fusion in primary position when a chronic deviation is small. In traumatic CN VI palsies or other well-defined causes, injection of the antagonist medial rectus muscle with botulinum toxin may (temporarily) permit fusion in primary position and reduce the risk of medial rectus contracture.