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Cranial Nerves III, IV, and VI: Oculomotor, Trochlear, and Abducens Nerves: Ocular Mobility and Pupils
Cranial Nerve III: Oculomotor
Clinical Vignette
A 37-year-old woman presented with a 2-day history of “blurry” vision on upward gaze and headache. One month previously, when she had experienced the same symptoms, sinusitis was diagnosed, and an antibiotic was prescribed; symptoms had resolved in 5 days.
Examination demonstrated impaired upward, downward, and medial movement in the right eye. There was mild right-sided ptosis, and the right pupil was slightly larger and reacted poorly compared with the left.
Magnetic resonance imaging (MRI) yielded normal results, but catheter angiography demonstrated a posterior communicating artery (p-com) aneurysm. At craniotomy the same night, the neurosurgeon reported fresh and old clot around a 10-mm aneurysm compressing the right oculomotor nerve. The aneurysm was clipped, and patient had an uneventful recovery with gradual resolution of the neuro-ophthalmologic findings.
Oculomotor palsy is most often associated with microvasculopathy due to diabetes mellitus, hypertension, or advanced age, so that its pool of potential victims is large. It is sometimes the harbinger of urgent, dangerous disease such as an expanding berry aneurysm. Even in idiopathic cases, the diplopia it typically produces is not only distressing for the patient but also disrupts daily activities. Even in cases where ptosis is severe enough to eliminate diplopia by blocking the vision of the affected eye, the impact on patients, both on an emotional and practical level, is severe.
The oculomotor nerves course from the ventral midbrain to the orbits. CN-III provides the general somatic motor efferent innervation controlling upper lid elevation and most of the extraocular movements upward, medially, and downward. In addition, CN-III carries the general visceral motor (parasympathetic) efferent innervation responsible for pupillary constriction and accommodation (near focus) of the crystalline lens.
CN-III begins at its nucleus in the midline upper midbrain. The nucleus is a lepidopterous collection of nine subnuclei located in the center of the rostral midbrain at the level of the superior colliculi ( Fig. 6.1 ). The most ventral of these subnuclei is the central caudate nucleus, a midline structure that innervates both levator palpebrae muscles. Uniquely, axons from the medial subnuclei or columns decussate completely to innervate the contralateral superior rectus muscles. The other six subnuclei, three left-and-right pairs, innervate ipsilateral extraocular muscles. The ventral subnucleus, intermediate column, and dorsal subnucleus, respectively, control the medial rectus (eye adduction), inferior oblique (intorsion and some elevation), and inferior rectus (depression).
Sometimes considered a subnucleus of CN-III, the Edinger-Westphal nucleus abuts the others rostrodorsally, residing at the ventral edge of periaqueductal gray matter. The Edinger-Westphal nucleus supplies the cholinergic efferents producing pupillary constriction and ciliary muscle contraction (lens accommodation). Afferents from the pretectal nuclei mediate the pupillary light reflex, whereas inputs influencing pupil constriction and lens accommodation in response to near visual stimulus originate from striate and prestriate cortex and the superior colliculus. When the pupillary fibers join the oculomotor nerve, they move exteriorly and dorsally within the nerve, a clinical continuation of the spatial relation of the Edinger-Westphal nucleus to CN-III.
The CN-III nucleus receives numerous afferents, including inputs from the paramedian pontine reticular formation for horizontal eye movement, the rostral interstitial nucleus of the medial longitudinal fasciculus (MLF) for vertical and torsional movements, and the vestibular nuclei. Other afferents come from the superior colliculi, the occipital cortex, and the cerebellum.
Axons from the CN-III nucleus gather into a fascicle that sweeps ventrally in an arc curving toward the medial surface of the cerebral peduncle, then passes through the red nucleus.
The nascent oculomotor nerve emerges from the medial surface of the cerebral peduncle to enter the interpeduncular cistern. It crosses the cistern for approximately 5 mm, passing under the posterior cerebral artery. The fibers subserving pupillary constriction are located externally at the caudal aspect of the nerve and are less prone to microvascular changes as the deeper fibers are. This arrangement is thought to explain the pupil's resilience to ischemia affecting CN-III and to its susceptibility in compression. The nerve follows beneath the p-com for 10 mm and then pierces the dura underneath the p-com before it passes the internal carotid artery (ICA) en route to the cavernous sinus.
The cavernous sinus is part of the intracranial venous system. It receives blood from the ophthalmic vein and sphenoparietal sinus, transmitting this flow to the superior and inferior petrosal sinuses. The left and right cavernous sinuses are connected via the intracavernous plexus; they also communicate with the basilar sinus and the pterygoid and foramen ovale plexuses. The cavernous sinus resides lateral to the pituitary gland, resting atop the roof and lateral wall of the sphenoid sinus. Besides venous blood, the space contains the intracavernous portions of CN-III, -IV, and -VI; the ophthalmic branch of CN-V and its maxillary nerve posteriorly; the ICA; and the sympathetic nerve fibers investing the adventitia of the ICA. CN-III, -IV, and -VI and the ophthalmic nerve all leave the cavernous sinus to enter the orbit via the superior orbital fissure.
Given the confluence of multiple structures into this relatively small sinus, cavernous lesions are prone to produce multiple cranial nerve palsies, often with pain or numbness in the ophthalmic distribution of CN-V. If the pathologic process is extensive, signs of venous obstruction in the orbit also develop (proptosis and chemosis).
CN-III typically divides into superior and inferior branches within the anterior cavernous sinus, thus entering the orbit as two distinct structures. The superior branch supplies the superior rectus and levator palpebrae muscles. The inferior branch provides somatic innervation to the medial and inferior recti and the inferior oblique, and it supplies the parasympathetic pupillary input to the ciliary ganglion, located superolaterally to the optic nerve. The parasympathetic axons from the Edinger-Westphal nucleus synapse here, with the postsynaptic neurons providing visceral motor control to the iris sphincter and the ciliary muscles via the short ciliary nerves.
Etiology and Pathogenesis
Etiologies for CN-III are broadly divided into two groups: those due to microvascular nerve infarction (e.g., diabetes mellitus) and those due to compression. There are also other, less frequent etiologies.
In the patient presenting with acute, severe headache and pupil-involved CN-III palsy, an expanding aneurysm, usually of the p-com, is the most important cause ( Fig. 6.2 ). The location of these aneurysms is usually at the origin of p-com from the ICA ( Fig. 6.3 ) and 90% of these aneurysms present with CN-III palsy. Aneurysm in other nearby arteries can likewise present as CN-III palsy, with up to 30% of acquired CN-III palsies being caused by aneurysms.
However, the majority of acquired CN-III palsies will be due to vascular compromise of some portion of CN-III, commonly affecting patients with known risk factors for vasculopathy or microvascular disease. In 60%–80% of microvascular CN-III palsy cases the pupil is spared. Typically, these palsies have a favorable prognosis and uncomplicated recovery within 2–4 months. Although common vasculopathies secondary to diabetes and hypertension are seen most frequently, attention should be paid to the possibilities of other systemic vasculitides, temporal arteritis, clotting disorder, and infiltrative processes.
Third-nerve palsies due to lesions of the nucleus or fascicle within the midbrain are usually part of a larger midbrain syndrome (see below). The usual etiologies of such palsies are stroke for older patients and inflammatory or demyelinating disease (i.e., multiple sclerosis) in the young.
Open or closed head injuries may lead to traumatic oculomotor nerve palsy. The suspected mechanism is traction or shearing where the third-nerve root is relatively fixed at its origin and at its entrance into the dura.
Typically, traumatic CN-III palsy is associated with severe frontal deceleration impact with loss of consciousness and, usually, skull fracture (e.g., unrestrained occupant in a motor vehicle accident). In cases where pupil-involving CN-III palsy is discovered after seemingly trivial injury, neurovascular imaging should be performed to detect a possible underlying skull base tumor, meningioma, or aneurysm.
Cavernous sinus thrombosis may produce a cranial polyneuropathy that features CN-III palsy. Often it is a septic complication of central facial cellulitis and a dreaded clinical entity typically producing proptosis, ophthalmoplegia, and optic neuropathy. Septic phlebitis of the facial vein or pterygoid plexus is the usual intermediary between cellulitis and infectious thrombosis.
Tolosa-Hunt syndrome is a painful ophthalmoplegia caused by idiopathic cavernous sinus inflammation, with most instances considered within the spectrum of inflammatory pseudotumor. It typically involves multiple cranial nerves and varies in degree over days. MRI of the cavernous sinus is needed to confirm the diagnosis, and treatment with high-dose corticosteroids is indicated once tumor and infection have been excluded.
Intrinsic, extrinsic, and metastatic tumors can cause third-nerve palsy. Carcinomatous or granulomatous meningitis can affect multiple cranial nerves in succession, often simulating Tolosa-Hunt syndrome.
Clinical Presentations
The classic presentation of a complete CN-III palsy is unmistakable: because of the unopposed actions of the superior oblique and lateral rectus muscles, the eye is turned outward and usually down. Upper-lid ptosis often requires that the lid be held up by the examiner to assess ocular motility.
The presence or absence of ipsilateral mydriasis (“pupil-involvement” or “pupil-sparing,” respectively) has traditionally been considered a major diagnostic consideration. CN-III palsies of compressive origin have pupillary involvement in the vast majority of cases and, if acute with severe headache, strongly suggest aneurysm as the etiology. Pupil-sparing usually implies temporary CN-III palsy due to microvascular ischemia. Patients with microvascular oculomotor palsy may report a mild ache in the ipsilateral brow, but occasionally the pain can be severe.
Motor involvement of CN-III palsies are generally characterized as complete, incomplete (where the innervated muscles show subtotal palsy), and, since the CN-III divides into superior and inferior rami just before its entrance into the orbit, divisional. “Superior division” CN-III palsy involves ipsilateral dysfunction of the superior rectus and levator palpebrae muscles, whereas an “inferior division” palsy has impaired downgaze, medial gaze, and on occasion, loss of pupillary constriction. Divisional palsies would seem to imply an orbital or anterior cavernous sinus pathologic site; however, more proximal intracranial disease is often responsible. Many cases will have negative imaging and recover well and are then assumed microvascular in etiology.
Incomplete CN-III palsies show partial losses of up-, down-, and medial-gaze, along with partial ptosis with some CN-III–innervated muscles more affected than others. In such cases—as the clinical vignette illustrates—recognition that the patient's ocular misalignment is a form of third-nerve palsy can be challenging. It is generally agreed that the presence of the pupil-sparing in such cases does not rule out compressive etiology.
A patient with an isolated medial rectus dysfunction (inability to adduct the eye) should not be considered to have an incomplete CN-III palsy. Most often, this condition is caused by internuclear ophthalmoplegia (see below). It may also be seen in cases of myasthenia gravis or from orbital disease involving the horizontal rectus muscles.
When the origin of third nerve palsy is at the nucleus, the presentation is one of ipsilateral medial rectus, inferior rectus, and inferior oblique dysfunction, with contralateral superior rectus weakness because of the decussation of axons from the medial column subnucleus. Because of bilateral lid innervation by the central caudate subnucleus, the eyelids exhibit either bilateral blepharoptosis or are normal, depending on the extent of the insult. In clinical practice, such cases are exceedingly rare.
With insult to the third-nerve fasciculus, clinical localization is often aided by the presence of other signs of midbrain dysfunction. CN-III fasciculus lesions at the red nucleus present as oculomotor palsy with crossed hemitremor, Benedikt syndrome. If the lesion extends to the medial lemniscus, there is also contralateral hypesthesia. Similar lesions with caudal extension into the brachium conjunctivum produce contralateral cerebellar ataxia or Claude syndrome. When damage extends ventrally into the basis pedunculi and the corticospinal tract, hemiplegia contralateral to the CN-III palsy occurs (Weber syndrome).
In comatose patients, unilateral mydriasis ( “blown” or Hutchinson pupil ) is indicative of supratentorial increased intracranial pressure (ICP), sufficient to force the uncus of the temporal lobe laterally and caudally to compress the third nerve against the anterior edge of the tentorial foramen (uncal herniation). In fact, using oculocephalic maneuvers, additional evidence of compressive CN-III palsy can be uncovered. Pupil checks and oculocephalic maneuvers need to be monitored frequently in any unresponsive patient, since uncal herniation can be rapidly fatal if not detected and addressed at its earliest sign. The laterality of the blown pupil does not always correlate with the side of the lesion.
Although a few cases exist of mydriasis as a possible sign of compressive third-nerve palsy in patients who are awake and alert, this remains exceedingly unlikely without evolving signs of altered consciousness and usually indicates another etiology, such as pharmacologic pupillary mydriasis or Adie tonic pupil (below).
Whereas microvascular CN-III palsy is generally followed by full recovery, the prognosis for traumatic or postoperative compressive CN-III palsy is guarded. If recovery occurs, it is usually marked by aberrant regeneration and synkinesis. The best-known example is the pseudo–von Graefe sign: the branch of CN-III that normally innervates the inferior rectus now synkinetically innervates the levator palpebrae, causing the upper lid to lift on downward gaze (clinically simulating the lid lag, or von Graefe sign, of Graves orbitopathy). Internal motor efferents can likewise be involved, resulting in a change of pupil size as gaze is shifted.
Occasionally, primary aberrant regeneration (aberrant regeneration without history of prior palsy) will be encountered. This finding is due to chronic compression of the third nerve, typically within or near the cavernous sinus usually due to meningioma and occasionally from an aneurysm of the intracavernous ICA. Adie tonic pupil is another example of aberrant regeneration affecting a facet of CN-III function with a probable intraorbital location within the ciliary ganglion and is discussed further in the section pertaining to pupils.
As opposed to the preceding discussion of isolated CN-III disease, the oculomotor nerve can be involved in cranial polyneuropathies, in which case the accompanying deficits typically help localize the etiology. Cavernous sinus syndrome typically affects CN-III, -IV, and -VI and the ophthalmic branch of CN-V. When the intracavernous carotid artery wall is also involved, sympathetic pupil dysfunction (Horner pupil) will result, producing miosis; the Horner pupil will be unnoticeable if CN-III–related mydriasis obscures it. The clinical history in the case of slowly expanding tumor in the cavernous sinus often includes chronically increasing diplopia, sometimes with pain or numbness in the CN-V ophthalmic distribution; in cases of inflammation or infection, the onset is usually dramatic and painful. Superior orbital fissure syndrome is often indistinguishable from cavernous sinus syndrome.
Lesions producing diminished vision, external ophthalmoplegia, orbital pain, and corneal hypesthesia and proptosis characterize orbital apex syndrome. In simplified terms, this syndrome is clinically characterized by findings of superior orbital fissure syndrome with a concomitant compressive optic neuropathy. It must be distinguished from pituitary apoplexy where sudden, painful visual loss due to chiasmal compression by pituitary hemorrhage is often accompanied by unilateral or bilateral CN-III palsy as impingement upon the adjacent cavernous sinuses evolves.
Differential Diagnosis
Myasthenia gravis, a disorder of somatic neuromuscular junction failure that does not affect the pupil, will occasionally simulate pupil-sparing third-nerve palsy. A history of diurnal variability, findings of inducible fatigability, and resolution of the “palsy” during intravenous administration of edrophonium chloride (Tensilon) is often sufficient to expose the diagnosis, which can then be confirmed by serum antibody testing and electromyography.
Chronic, progressive external ophthalmoplegia (CPEO) presents as slowly progressive bilateral ptosis and loss of extraocular movements, usually without diplopia. CPEO has been associated with specific mutations of mitochondrial and nuclear DNA and can be part of a larger syndrome, oculopharyngeal dystrophy. The Kearns-Sayre variant of CPEO includes pigmentary retinopathy with nyctalopia, hormonal dysfunction, and most importantly cardiac conduction disorders necessitating cardiology evaluation.
The Miller Fisher variant of Guillain-Barré syndrome produces an external ophthalmoplegia that may be initially confused with CN-III palsy; the presence of viral prodrome, ataxia, areflexia, cerebrospinal fluid albuminocytologic dissociation, and in some instances positive serum anti-GQ1b IgM and IgG antibodies will confirm the diagnosis.
Patients with internuclear ophthalmoplegia have inability to move the ipsilateral eye into adduction when attempting horizontal gaze to the contralateral side. The responsible lesion is in the MLF, interrupting the interneurons traveling from the CN-VI nucleus to the CN-III ventral subnucleus that innervates the medial rectus (see discussion of CN-VI anatomy, below). Such patients are often assumed to have “medial rectus palsy”; however, such a variant of CN-III palsy is rarely if ever seen clinically, and the preservation of adduction during convergence to near stimulus (mediated by the mesencephalon) in internuclear ophthalmoplegia serves to confirm its central nervous system supranuclear origin.
Duane syndrome is an example of a congenital aberrant innervation. In affected individuals, prenatal abducens nerve dysgenesis or injury causes subsequent misdirected CN-III innervation of the lateral rectus. Therefore attempted lateral eye movement results in simultaneous stimulation of the medial and lateral recti, causing variable eye movement, measurable globe retraction into the orbit, and consequent pseudoptosis. In type II Duane syndrome, the combination of poor adduction and pseudoptosis during globe retraction may simulate CN-III palsy. The congenital nature of this condition is most easily deduced by the absence of symptomatic diplopia in lateral gaze despite the presence of incomitant strabismus.
Patients with isolated ptosis are often screened for the presence of CN-III palsy. The most common cause of ptosis, typically encountered in patients older than age 50 years—but occasionally seen in younger patients with a history of frequent eye rubbing—is aponeurotic ptosis or levator dehiscence, a lengthening of the tendon (aponeurosis) connecting the levator palpebrae muscle to the upper lid. Aponeurotic ptosis is particularly common in patients who have undergone cataract surgery. In those patients who, in addition, experienced intraoperative iris injury with postoperative mydriasis, erroneous suspicion of a partial compressive CN-III palsy can be easily prompted.
Marcus Gunn jaw-winking is a syndrome of congenital aberrant innervation of the levator palpebrae muscle by the motor neurons of CN-V that innervate the pterygoid muscles of the mandible. The typical patient will have ptosis that partially resolves with lateral and forward jaw movements with costimulation of the levator.
In the traumatic setting, ophthalmoplegia due to CN-III palsy must be distinguished from that due to orbital disease (e.g., orbital floor fracture with entrapment of the inferior rectus muscle).
Diagnostic Approach
A spared pupil in otherwise complete CN-III palsy is highly suggestive of a microvascular cause. However, in cases of a recent incomplete extraocular CN-III palsy, the absence of pupil involvement could suggest an evolving process for which imaging is required.
Once aneurysm has been excluded, in those patients without clear precipitants, testing for diabetes mellitus, hypertension, vasculitis and other inflammatory disease, clotting disorders, spirochetal disease (syphilis and Lyme disease), and myasthenia gravis is recommended. Even in patients with microvascular CN-III palsy without evidence of causative disease, consideration may be given to reevaluate already defined cerebrovascular risk factors.
Any patient presenting with diplopia, initially thought to be related to a cranial mononeuropathy, must have careful examination of the adjacent cranial nerve to exclude their involvement. Also, patients with apparently isolated CN-III palsy should be checked for signs of ataxia, areflexia, or contralateral rubral tremor, hemiparesis, or hypesthesia. Similarly, patients presenting with new upper facial pain or numbness must always be checked for impaired eye movements and corneal hypesthesia to exclude early cavernous sinus syndrome.
Management and Therapy
The management of symptomatic intracranial aneurysm is usually urgent, via endovascular or surgical intervention if the general state of the patient permits (see Chapter 56 ). Management of microvascular palsy usually centers on prevention of recurrent events via reduction of risk factors. Optimization of any causative disease, such as diabetes, is crucial, and daily aspirin is often recommended. Therapy for other underlying causes of CN-III palsy will vary, appropriate to etiology.
Visual management of nonhealing CN-III palsies is complicated by the number of paretic extraocular muscles involved, as ocular misalignment changes significantly depending on the direction of gaze. Prismatic spectacles are often unavailing, except in cases of minimal residual misalignment. Strabismus surgery, often involving two or three staged procedures, has the limited goal of stable relief of diplopia in primary gaze only. Often the simplest management tool, if acceptable to the patient, is occluding vision through a fogged lens or patch on the affected eye to eliminate diplopia, if the ptosis does not already accomplish that.
Cranial Nerve IV: Trochlear
Clinical Vignette
A workman, bent over his work, sustained left occiput blunt head trauma and scalp laceration when a coworker dropped a tool from above. Diplopia and headache subsequently developed.
Examination revealed poor depression of the right eye in leftward gaze. Prismatic spectacle lenses were prescribed to alleviate the diplopia. After a few months, the patient reported that his vision had returned to normal.
This vignette describes isolated trochlear nerve (CN-IV) injury with relatively mild closed head trauma. Often the most benign of the cranial neuropathies, particularly those related to extraocular muscle function, it tends to recover fully over a period of weeks or months.
The CN-IV nuclei are located at the level of the inferior colliculi in the lower midbrain off the midline at the ventral edge of the periaqueductal gray. The nuclei are crossed; the left trochlear nucleus innervates the right superior oblique and vice versa.
Axons emanating from the trochlear nucleus arc dorsally around the periaqueductal gray into the tectum of the midbrain, where they cross the midline and then emerge laterally beneath the inferior colliculus at the medial border of the brachium conjunctivum as CN-IV. It then completely decussates and exits the brainstem from its dorsal aspect, a unique feature among the cranial nerves. It passes through the quadrigeminal and ambient cisterns and then runs along the free edge of the tentorium. It enters the orbit via the superior orbital fissure and innervates a single extraocular muscle, the superior oblique.
The superior oblique is chiefly a depressor of the globe and is most active when the eye is adducted and depressed. It has a secondary function of intorting the eye during ipsilateral head tilt and is a weak abductor of the eye in downgaze ( Fig. 6.4 ). Therefore CN-IV palsy will produce ipsilateral loss of depression (hyperopia) and excyclotorsion of the globe.
Etiology and Pathogenesis
Trauma is the most frequent cause of CN-IV palsies. Traumatic palsies may be bilateral, but most often one side is spared or recovers so that patients are left with unilateral dysfunction. The frequent association of trauma with CN-IV palsy may imply that the thin dorsal tectum is vulnerable to traumatic forces causing shear injury between the emerging nerves and the colliculi or the cerebellar tentorium or direct injury from a hydraulic pressure wave transmitted through the aqueduct. MRI demonstration of tectal subarachnoid hematoma in traumatic trochlear palsy supports this theory. In addition, a pathologic study has shown that, with sufficient force, avulsion of the CN-IV root from the pons can occur.
The nucleus and fasciculus of the trochlear nerve lie within the pons; in this location, CN-IV palsies may result from stroke, demyelination, and tumor. Lesions of the fascicle, rarely seen clinically, produce a contralateral CN-IV palsy and an ipsilateral Horner syndrome due to coinvolvement of the descending first-order pupillary sympathetic axons passing through the pontine tegmentum. The trochlear nerve fasciculi decussate just dorsal to the sylvian aqueduct, and tumors or stroke in this area will produce bilateral trochlear palsies.
In the subarachnoid space, CN-IV can be affected by carcinomatous meningitis, by aneurysm (especially of the superior cerebellar artery; see Fig. 6.2 ), or by dolichoectasia of the basilar artery. The nerve itself may be the site of schwannomas. Once within the dural canal leading to the cavernous sinus, the nerve may be affected by tumors, especially meningioma. Compression of CN-IV can occur at the cavernous sinus itself, by dissections or aneurysm of the carotid artery, by extension of sellar and orbital tumors, and by metastases. Typically CN-IV, -III, -VI, and the ophthalmic branch of CN-V are involved in cavernous sinus lesions.
In cases where imaging reveals no structural cause of CN-IV palsy and where there is no history of trauma, microvascular ischemia is the usual assumed etiology. Patients with diabetes, hypertension, vasculitis, sarcoidosis, or treponemal infection may present with seemingly “idiopathic” palsies.
Clinical Presentations
Patients with trochlear palsy have hypertropia or impaired ability to depress the eye on the involved side. Weakness of depressor function of the superior oblique is exaggerated with medial downward gaze or when the head is tilted toward the side of palsy.
Normally during head tilt to one side, the ipsilateral superior oblique is activated to accomplish incyclotorsion of the eye, keeping the retina relatively level despite the head shift. The medial rectus is activated simultaneously, so that the incyclotorsion of the superior oblique is not accompanied by usual depressing of the globe. In trochlear palsy, then, when the head is tilted toward the palsied side, abnormal excyclotorsion is emphasized, magnifying both the hypertropia and diplopia. This pattern of incomitant strabismus is summarized as “hypertropia worse with gaze away and with tilt toward the affected side.”
Patients with CN-IV palsy often adopt a secondary torticollis, offering a diagnostic clue. Patients prefer a chin-down posture with the head tilted away from the palsy, so that the affected eye is in up and out, where the superior oblique normally has the least action, and its palsy matters the least. Because this posture minimizes the visual consequences of CN-IV palsy, congenital CN-IV palsies are often undiagnosed for decades. A diagnosis in adulthood may be made after intermittent diplopia develops from progressive asthenopia or when treatment for torticollis is sought. The presence of the characteristic head tilt in childhood photographs often confirms the congenital nature of the palsy.
In most cases of CN-IV palsy, there is a history of trauma. A high frontal head impact with contrecoup forces at the dorsal tectum, occipital impact producing more direct injury, or coccygeal impact transmitted up a straight spinal column are all encountered. Occasionally, the appearance of vertical diplopia after frontal head trauma will prompt suspicion of orbital floor “blow-out” fracture before CN-IV palsy is uncovered.
The amount of force needed to produce traumatic CN-IV palsy seems variable, and, in contradistinction to traumatic CN-III palsy, impact sufficient to produce alteration in consciousness is not required. An acquired trochlear palsy after minor head trauma should still, however, prompt suspicion of an undiagnosed mass lesion, producing a “pathologic” palsy in an already damaged nerve.
Patients with bilateral CN-IV palsy complain of rotational instead of vertical diplopia. Loss of incyclotorsion for both eyes causes images seen by the left eye to rotate clockwise compared with those seen by the right eye. Most patients with bilateral involvement will note occasional vertical diplopia: right eye image above left eye image with left head tilt or rightward gaze, and vice versa. Often, esotropia is seen in downgaze as well, because of loss of the abducting action of the superior obliques. They may adopt a chin-down head position without horizontal tilt.
A lesion interrupting both the predecussation trochlear fasciculus and the ipsilateral central tegmental (pupillary sympathetic) tract within the tectum produces an ipsilateral Horner syndrome with crossed CN-IV palsy. CN-IV palsy has occurred in the setting of idiopathic intracranial hypertension and after lumbar puncture—presumably because of tractional mechanisms—both with CN-VI coinvolvement. It can also occur in conjunction with CN-III involvement in spontaneous intracranial hypotension.
Perhaps because of their relatively fixed location within the lateral wall of the cavernous sinus, the trochlear and trigeminal nerves can be injured concomitantly. Patients with a posteriorly draining carotid–cavernous fistula may present with painful superior oblique dysfunction along with oculomotor nerve palsy, presumably due to local cavernous distention.
Differential Diagnosis
Other entities that produce vertical binocular diplopia with hypertropia may be initially confused with CN-IV palsy; myasthenia gravis is one such mimic. However, the pattern of changing misalignment in different directions of gaze will usually serve to distinguish true trochlear palsies from its simulators.
Restrictive diseases affecting the inferior rectus muscle (such as thyroid-related orbitopathy, orbital floor fracture with entrapment of the muscle, or injury from local anesthetic for cataract surgery) produce vertical diplopia; such diplopia, however, worsens in upgaze. Restrictive disease of the inferior oblique is a far better mimic, as patients would have ipsilateral hyperopia with excyclotorsion and worsening on attempted downgaze.
Injury to the orbital trochlea (through which the superior oblique tendon passes) typically produces Brown tendon sheath syndrome, with the eye shooting into downgaze on adduction because the tendon remains tight even when the muscle relaxes; however, on occasion, the injured trochlea will not allow the tendon to retract in response to superior oblique retraction, perfectly simulating CN-IV palsy. History of orbital trauma and trochlear abnormality on orbital imaging will serve to clarify the diagnosis.
Skew deviation due to imbalance of the otolithic inputs to the vestibulo-ocular system can also produce vertical misalignment. In such cases, reclining the patient to a supine position may eliminate the hypertropia.
Diagnostic Approach
Diagnosis of unilateral CN-IV palsy is made when ipsilateral hypertropia is demonstrated to worsen in downward gaze, contralateral gaze, and ipsilateral head tilt. Cases of bilateral trochlear palsies may present the seeming paradox of no hypertropia in primary gaze when the head is straight. However, these patients demonstrate a left hypertropia on right gaze and left head tilt, and right hypertropia on left gaze with a right head tilt.
Blood testing for infection, abnormal clotting, and systemic inflammation is usually done in nontraumatic cases. Patients with isolated CN-IV palsies may be observed for spontaneous improvement over 3–4 months if the history indicates a likely etiology (e.g., trauma or known diabetes); otherwise, neuroimaging is done upon diagnosis. Even in cases with a presumed etiology, nonresolution over time usually prompts imaging unless congenital CN-IV palsy is strongly suggested by history and examination findings (e.g., vertical fusional amplitude greater than 4 diopters and photographic evidence of life-long compensating head tilt).
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