Trochlear Nerve Palsy (Fourth Nerve Palsy)

Background

Trochlear nerve palsy is mentioned in ophthalmology texts dating to the mid nineteenth century. However, it received little more than a brief mention and was no doubt an underrecognized entity. In 1935, Bielschowsky correctly noted that trochlear nerve palsy was the most common cause of vertical diplopia and introduced his classic head-tilt test. With greater clinical interest, the number of identified fourth nerve palsies has increased.

Key Considerations

A fourth nerve palsy is a common cause of binocular vertical oblique diplopia in isolation.

The fourth cranial nerve exits dorsally and has the longest intracranial course.

An isolated fourth cranial nerve palsy can usually be diagnosed using the three-step test.

The primary action of the superior oblique muscle is intorsion.

• References

History of the Procedure

Surgical therapy for this condition has been refined over the last 30 years. The introduction of the Harada-Ito procedure in the 1960s and Knapp's surgical approach in the 1970s enhanced the ability to successfully treat this challenging clinical entity.^[1]

• References

Problem

The fourth cranial nerve innervates superior oblique muscle, which intorts, depresses, and abducts the globe.^[2] Fourth nerve palsy can be congenital or acquired, unilateral or bilateral, each of which presents with a distinct clinical picture.^[3] Clinicians must carefully assess the patient to determine both etiology and extent of disease. Acquired weakness of this muscle usually leads to complaints of binocular vertical or oblique diplopia, sometimes with a torsional component. Surgery may be required to treat these patients. Thorough assessment and careful preoperative planning maximize the chances of a successful surgical outcome.

• References

Epidemiology

Frequency

Most cases of isolated fourth nerve palsy are believed to be congenital.^[4] However, estimating the true frequency of congenital fourth nerve palsy is difficult. Many patients compensate with use of head-tilt or large fusional amplitudes; therefore, it may not present to an ophthalmologist until adulthood, when their fusional control begins to deteriorate.

Some of the best information regarding the incidence of acquired fourth nerve palsy can be found in the Mayo Clinic series. Several studies, performed over the last 4 decades, reported the incidence and etiology of acquired cranial nerve palsies in adult and pediatric patients. Trochlear nerve palsy was less common than abducens or oculomotor palsies. Of 4,373 acquired cases of extraocular muscle palsy in adults, there were only 657 cases of isolated fourth nerve disease.^[5] Fourth nerve palsy was also the least frequent in pediatric population. In a similar Mayo Clinic study of 160 children, 19 of them had isolated fourth nerve palsy.^{[6, 7]}

• References

Etiology

The most common cause of congenital trochlear nerve palsies is congenital cranial dysinnervation syndrome, followed by an abnormal superior oblique tendon.^{[8, 9, 10]}

The most common cause of acquired isolated fourth nerve palsy, after idiopathic, is head trauma.^{[11, 12, 13]}

One must consider the possibility of underlying structural abnormalities (eg, skull based tumor) if fourth nerve palsy results after only minor trauma.

Microvasculopathy secondary to diabetes, atherosclerosis, or hypertension also may cause isolated fourth nerve palsy.^[14]

There are rare reports of thyroid ophthalmopathy and myasthenia gravis mimicking an isolated fourth nerve palsy. These patients eventually develop other findings, unmasking the underlying diagnosis.

Tumor, aneurysm, multiple sclerosis, or iatrogenic injury may present with isolated fourth nerve palsy that may evolve over time to include other cranial nerve palsies or neurologic symptoms.^[15]

Fourth nerve palsy may become manifest after cataract surgery. Patients with underlying, well-controlled, and asymptomatic fourth nerve palsy may decompensate gradually as they lose binocular function resulting from cataract. Following restoration of good vision, these patients become aware of diplopia.

• References

Pathophysiology

Congenital Trochlear Nerve Palsy

A series of high-definition MRI studies by Yang et al have identified two etiologies of congenital trochlear nerve palsies, with the most common being congenital cranial dysinnervation syndrome. This syndrome was present in 73% of congenital trochlear nerve palsy cases and is characterized by absence of the trochlear nerve and secondary atrophy of the superior oblique muscle. The remaining 27% had a normal trochlear nerve and superior oblique muscle size, but an abnormal superior oblique tendon, which may explain the variations in superior oblique tendon laxity encountered surgically.^{[8, 9, 10]}

Helveston, in a series of 36 congenital superior oblique palsy patients, found 33 abnormal superior oblique tendons.^[16] The tendon may be abnormally lax, have an abnormal insertion, or be absent altogether.

Acquired Trochlear Nerve Palsy

The long course of the trochlear nerve makes it especially susceptible to injury in association with severe head trauma. Contrecoup forces can compress the nerve against the rigid tentorium, which lies adjacent to the nerve for much of its course. Injury to nerve can occur anywhere along its course from midbrain to orbit. Lesions at the nucleus cause contralateral superior oblique palsy, since the nerve decussates at anterior medullary velum, caudal to inferior colliculus. Midbrain trauma can produce bilateral superior oblique palsy by contusive injury of decussation of nerves. Compression or ischemia at this site also can produce bilateral palsy.

See the image below.

View Image

Patient with traumatic bilateral superior oblique palsy; note right hypertropia on right head tilt and left hypertropia on left head tilt.

One should suspect a lesion to the trochlear nucleus or fascicle when palsy is associated with a contralateral Horner syndrome or an ipsilateral relative afferent pupillary defect (RAPD; especially without concomitant visual loss [ie, tectal RAPD]). This is due to the close proximity of the sympathetic pathways in the dorsolateral tegmentum of the midbrain and the pretectal afferent pupillary fibers that run through the superior colliculus.

Tumors or aneurysms causing compressive injury in the subarachnoid space generally damage adjacent structures and produce associated neurologic signs. The same is true of lesions in area of cavernous sinus and orbital apex, which generally produce multiple cranial neuropathies. In rare cases, fourth nerve palsy may result from any cause of increased intracranial pressure such as pseudotumor cerebri or meningitis. Direct orbital injury can result in a clinical picture that resembles fourth nerve palsy, but superior oblique weakness in this setting most likely is due to direct damage to muscle or tendon.

• References

Presentation

The superior oblique muscle intorts, depresses, and abducts the globe.

In acquired lesions of fourth nerve, patients report vertical, torsional, or oblique diplopia. Diplopia is usually worse on downgaze and gaze away from side of affected muscle.

In case of trauma, patients usually report symptoms immediately after regaining consciousness.

Torsional diplopia and downgaze horizontal diplopia may be predominant complaints in bilateral palsies.^[17]

Patients may adopt a characteristic head tilt, away from affected side to reduce their diplopia. Interestingly, some patients develop head tilt toward side of lesion. This so-called paradoxic head tilt is used to create a wider separation of images, which allows the patient to suppress or ignore one image. Old photographs may provide clear documentation of a head tilt in congenital fourth nerve palsy.

Congenital fourth nerve palsies may present with several unique findings, as follows:

• Patients with long-standing head tilt present during early childhood may develop facial asymmetry. Characteristically, there is shallowing of face between lateral canthus and side of mouth on the side of head tilt. Any condition that leads to torticollis in early life may result in similar facial asymmetry.
• Patients with congenital palsies also tend to develop large, vertical fusional amplitudes, and they may have lack of subjective torsion even when large amounts of fundus torsion are present.

Patients with congenital superior oblique palsy who are lacking a trochlear nerve develop a head tilt at an earlier age. Patients with congenital superior oblique palsy who have a normal trochlear nerve demonstrate more overelevation in adduction and frequent dissociated vertical deviation.^[8]

See the image below.

View Image

A 2-year-old girl with compensatory left head tilt due to congenital right superior oblique palsy.

• References

Indications

For patients with decompensating congenital fourth nerve palsy, indications for intervention include cosmetically or functionally unacceptable head position, and onset of increasing frequency of diplopia.

Patients with acquired disease from tumors or compressive lesions are usually significantly disturbed by symptoms and are likely to require prism or, in some cases, surgical intervention.

• References

Relevant Anatomy

The trochlear nucleus is located in tegmentum of midbrain, at the level of inferior colliculus.^{[11, 2]} The trochlear nerves decussate at anterior medullary velum in the roof of aqueduct before exiting from dorsal aspect of midbrain. The fourth nerve courses between posterior cerebral and superior cerebellar arteries before entering the cavernous sinus. The fourth nerve then enters the orbit through superior orbital fissure, outside annulus of Zinn. From here, the nerve crosses medially over levator palpebrae superioris and superior rectus muscles before entering the belly of superior oblique muscle.

The superior oblique muscle originates from the orbital apex, above the annulus, and runs along superonasal aspect of orbit before becoming a tendinous cord. The superior oblique tendon then passes through trochlea and abruptly turns laterally and posteriorly to insert on the globe. The tendon is cordlike as it passes beneath nasal border of superior rectus but fans out to form a broad insertion.

When performing a superior oblique tenotomy, the superior rectus muscle insertion may be used as a landmark. The portion of tendon that is cut during the tenotomy may be isolated by dissecting to a point approximately 8-12 mm posterior to nasal aspect of superior rectus insertion. Broad superior oblique insertion, which is 10-18 mm in length, has great functional importance. Anterior fibers act mainly to intort the globe and do little to abduct or depress the eye. Conversely, more posterior fibers are responsible for abduction and depression but have little torsional action. Surgical procedures designed to alleviate torsional diplopia, such as the Harada-Ito procedure, consist of advancing only anterior fibers of tendon insertion.

• References

Contraindications

Patients with microvascular disease have a high likelihood of resolution. These patients may be observed and advised to patch 1 eye or use monovision lenses to minimize their symptoms.

Similarly, patients who have traumatic fourth nerve palsy may be observed for 6 months prior to surgical intervention because of the possibility of spontaneous resolution; however, some traumatic palsies may recover as late as 1 year after injury.^[18]

• References

Prognosis

The prognosis of a fourth nerve palsy depends on the underlying etiology. Congenital palsies are long standing and often remain static. Acquired, demyelinating (rare), traumatic, ischemic (microvascular), and idiopathic palsies usually resolve over time. The prognosis of fourth nerve palsies due to a structural lesion depend on the treatment of the underlying lesion. Most patients with symptoms that do not recover spontaneously can improve with prism or surgery.

• References

Patient Education

Patients should be advised on the etiology and prognosis of the fourth nerve palsy. Prism or surgical therapy can be considered in patients who have stable and unresolved ocular deviations.

• References

History

Obtain a detailed history concerning characteristics of the diplopia: onset, duration, vertical or horizontal, monocular or binocular, and positions that improve or worsen the diplopia. This can help differentiate a new onset of fourth nerve palsy from a congenital condition that has decompensated. Patients with trochlear nerve palsy typically have worse diplopia on downgaze and gaze opposite the affected eye. If the onset is due to trauma, determine the mechanism of injury. Blunt trauma to the head, especially directly at the orbit, is a common cause of acquired trochlear nerve palsy.

A detailed medical history and review of systems can aid in detecting the root cause of the palsy. Determine risk factors for stroke, including any history of hypertension, dyslipidemia, diabetes mellitus, smoking, and past cardiovascular incidents. Surgical history should be assessed for past intracranial or orbital surgeries. Constitutive symptoms such as fever, malaise, and neck stiffness suggest meningitis. Neurologic findings can indicate a compressive lesion of the trochlear nucleus, fascicle, or nerve. Diagnosis of other diseases such as HIV infection and demyelinating diseases is pertinent as they have also been associated with fourth nerve palsy. In older patients, giant cell arteritis should also be ruled out.^{[19, 20]}

• References

Physical Examination

Inspect the patient for compensatory torticollis, typically to the opposite side of the affected superior oblique. However, some patients tilt toward the side of the affected muscle to create greater separation and suppression of the double vision. Other patients have no torticollis because of poor vision or existing amblyopia.

The three-step test can be useful in evaluation of vertical diplopia caused by a paretic cyclovertical muscle. However, results of this test can be misleading in the setting of restrictive ophthalmopathy, multiple muscle involvement, skew deviation, and an absent trochlear nerve, so results should be interpreted cautiously and combined with imaging findings and a detailed history for definitive diagnosis.^{[21, 22]} Each step reduces by half the number of possible affected muscles until only 1 remains, as follows:

• The first step is to identify the hypertropic eye in primary gaze. This implicates depressors of hypertropic eye or elevators of hypotropic eye.
• The second step is to ascertain if hypertropia is worse on left gaze or right gaze. This will identify 4 muscles that act in that direction of gaze.
• The third step is to determine if hypertropia is worse on right head tilt or left head tilt.

The Bielschowsky head-tilt test stimulates intorsion of globe on the side to which head is tilted and extorsion of globe on the side away from which head is tilted.^[23] Intorters and extorters of each globe have opposite vertical functions, and, when there is a paretic muscle, unopposed vertical action of other muscle makes hyperdeviation more apparent in that field of action. Only the paretic muscle will have been implicated in each step of the test.

In case of bilateral fourth nerve palsy, interpretation of 3-step test may be confusing.^[24] Right hypertropia manifests on right head tilt, and left hypertropia manifests on left head tilt. Other findings, such as V-pattern esotropia and large amounts of excyclotorsion, also are suggestive of bilateral disease.

Cyclotorsion may be measured using double Maddox rod test.^{[11, 25, 26]} Details are as follows:

• Patients are seated in a dark room to minimize their reliance on environmental cues.
• Red Maddox rod is placed before each eye with axes oriented obliquely at about 5-10° from the vertical. A prism could be placed in front of one eye to vertically separate the images; this would help the patient to compare the two images better.
• Patient is asked to rotate 1 frame until the 2 lines are parallel.

Patients with bilateral disease typically show more than 10° of excyclotorsion.

The upright-supine test can differentiate skew deviation from other causes of vertical strabismus. Measure the patient’s vertical misalignment while in the upright position. Then, measure again while the patient is supine. A decrease of more than 50% in supine is a positive result. The vertical misalignment caused by skew deviation depends on head position, whereas it would not change in trochlear nerve palsy. Based on a study by Wong et al, this test has 76% sensitivity and 100% specificity.^[27]

Examine fundus photography for ocular torsion. The disc-fovea angle is used to estimate the amount of ocular torsion and can be measured as the angle between the line from the optic disc center to the fovea and a horizontal line through the optic disc center.^[26] Dieterich et al discovered a 2°-8° ocular torsion in patients with trochlear nerve palsy, and Lefevre et al observed 10.7° ± 3.8° of excyclotorsion in the paretic eye and 8.8° ± 5.7° in the nonparetic eye.^{[28, 29]} In a study by Roh et al, this test was more sensitive (100%) than both the Lancaster red-green test and double Maddox rod test.^[30]

• References

Approach Considerations

The patient’s history should be taken into consideration when considering further workup. Acquired isolated and presumed ischemic or posttraumatic fourth nerve palsy often resolves spontaneously.^[19] Neuroimaging should be considered for nonisolated, bilateral, progressive, or unexplained fourth nerve palsies. If observation is elected (eg, ischemic, traumatic, congenital) but the fourth nerve palsy does not resolve, further testing including neuroimaging (eg, MRI/MRA, CT scanning of the head and orbit), along with other laboratory studies, may be indicated.

• References

Laboratory Studies

General laboratory studies include fasting glucose and HbA1C.

Myasthenia gravis: Anti-acetylcholine receptor antibodies, anti-striated muscle antibody, anti-MuSK antibody, anti-LRP4 antibody

Thyroid eye disease: Free T4, TSH, thyroid receptor antibody, TSH-binding inhibitor immunoglobulin, anti-TPO antibodies

Giant cell arteritis: ESR, CRP, temporal artery biopsy

• References

Imaging Studies

MRI/MRA

MRI can be used to identify lesions or inflammation that affects the parenchyma or brainstem. These lesions can include ischemia or a tumor.

MRA illustrates blood flow and can aid in identifying an aneurysm.

CT scanning of head and orbit

CT scanning can help identify disease within the orbit or skull. It is sensitive in detecting calcifications and intracranial aneurysms.

• References

Medical Therapy

Prisms may be used for patients with small deviations and diplopia without torsional component. Incomitance of deviation often limits usefulness of this therapy.

Botulinum toxin also has been studied in treatment of fourth nerve palsy.^[31] It is a neuromuscular agent that acts presynaptically to block neurotransmitter release and results in muscle weakening. Use of this agent as primary therapy for fourth nerve palsy has been discouraging. However, it may be used best to correct residual deviation after strabismus surgery to delay or avoid further surgery.

BOTOX® is purified botulinum toxin A, derived from a culture of the Hall strain of Clostridium botulinum. It acts by binding to receptor sites on motor nerve terminals and inhibiting the release of acetylcholine. BOTOX® may be used for the treatment of strabismus and blepharospasm in patients 12 years and older. It is pregnancy category C.

Side effects for use in strabismus include ptosis and vertical deviation by action at extraocular muscles close to the site of injection. Injection should be performed under direct visualization during a surgical procedure or with the aid of electromyography.

Each vial of BOTOX® contains 100 units of botulinum toxin A in a vacuum-dried form. It needs to be reconstituted using preservative free 0.9% sodium chloride as the diluent. Doses used in strabismus range from 1.25-5 units, depending on the amount of deviation.

• References

Surgical Therapy

In 1970s, Knapp developed a surgical approach for superior oblique palsy.^[1] He classified superior oblique palsy by determining field of gaze in which deviation was greatest. Based on this classification, he recommended operation on the muscle or muscles that acted in this direction of gaze.

See the images below.

View Image

A 2-year-old girl with compensatory left head tilt due to congenital right superior oblique palsy.

View Image

Postoperative photo of same girl; note marked improvement of head tilt.

Plager described a tailored treatment plan that evolved from Knapp's recommendations, with some additions based on more recent operative algorithms.^[32] For a deviation of less than 15 prism diopters, single muscle surgery usually suffices. If there is any inferior oblique overaction, inferior oblique weakening by tenotomy, recession, disinsertion/disinsertion- myectomy, and anterior transposition are all acceptable choices. There is no consensus on which procedure is superior.^[33] Without any evidence of inferior oblique overaction, another muscle may be chosen. In case of ipsilateral superior rectus restriction, a superior rectus recession would be indicated. Superior oblique tendon tuck is preferred if significant tendon laxity is present, as has been described in congenital cases. Contralateral inferior rectus recession is chosen if there is no evidence of superior rectus restriction or superior oblique tendon laxity. This is an especially useful procedure when deviation is greatest in downgaze.

A critical decision to make in the treatment of fourth nerve palsy is whether to perform a one-muscle or two-muscle surgery. Nash et al compared one-muscle versus two-muscle surgery for moderate-angle hyperdeviations (14-25 prism diopters) due to unilateral fourth nerve palsy in a retrospective chart review of 73 patients. They concluded no clear advantage of two-muscle surgery for motor outcomes or for diplopia correction. Less-symptomatic diplopia undercorrections were more common with one-muscle surgery, while two-muscle surgery resulted in fewer more-symptomatic diplopia overcorrections.^[34]

Two muscle surgery generally includes weakening of ipsilateral inferior oblique, as well as a procedure on ipsilateral superior rectus, superior oblique, or contralateral inferior rectus. For large deviations, 3-muscle surgery may be considered. Inferior oblique and contralateral inferior rectus should be weakened. Then, the surgeon may choose to operate on superior oblique or superior rectus, based on intraoperative findings.

Modified Harada-Ito procedure is useful for patients with large excyclotorsional deviation. This is likely to be the case for patients with bilateral superior oblique palsy, and bilateral surgery should be performed.^[35] In this procedure, the superior oblique tendon is split and anterior fibers are advanced anteriorly and laterally.

• References

Preoperative Details

Careful assessment of deviation in all fields of gaze should be performed.

Multiple measurements should be taken to ensure that deviations are stable.

Ductions should be evaluated to determine if there is inferior oblique overaction.^[36]

Presence of V-pattern esotropia is highly suggestive of bilateral superior oblique palsy.

It may not be possible to determine if there is superior rectus restriction in clinic, and this test may be performed in operating suite.

Photographs that show head position and ocular motility findings, including head tilts, are useful for documentation.

Infants presenting with torticollis may be suspected of having superior oblique palsy.

To differentiate true cases of strabismus from neuromuscular causes of torticollis, patch test may be performed in the office. After 20 minutes of monocular occlusion, the child is reevaluated, still wearing the patch. If head tilt was adopted for fusional purposes, it will be reduced after patching.

There is a low risk of amblyopia in affected children presumably because they can achieve intermittent fusion by using head tilt and large fusional amplitudes. Loss of compensatory head position by a child suggests loss of fusion and may be associated with development of amblyopia.

• References

Intraoperative Details

Patients with congenital superior oblique palsy often have abnormally lax superior oblique tendon. Exaggerated, forced duction test described by Guyton can be performed intraoperatively to determine if there is any degree of tendon laxity relative to normal eye, as follows:^[37]

• This test is performed by grasping the eye obliquely at 2- and 8-o'clock positions for the left eye and at 4- and 10-o'clock positions for the right eye.
• Eye is rotated superiorly and medially while simultaneously depressing the eye into the orbit. This places superior oblique tendon on maximal tension.
• Eye is rolled back and forth over the tendon to ascertain its tension.
• Performing this test prior to the start of case will guide the surgeon to determine eyes that will benefit from a superior oblique tendon tuck.
• Of equal importance is that it will identify those patients who are at risk for developing a postoperative Brown syndrome.
• Tendon tucks should be performed only for markedly lax tendons. Tuck should be enough to match tension of the normal eye's tendon.

Any surgeon who performs oblique muscle surgery should be familiar with anatomy, landmarks, and appropriate approaches to these muscles.

Visualization is more difficult than with rectus muscle surgery, and injury to adjacent nerves, blood vessels, and other extraocular muscles may occur. Use of headlight can improve visualization.

• References

Postoperative Details

Without careful preoperative assessment, bilateral asymmetric superior oblique palsy may be mistaken for unilateral palsy. After surgery for unilateral palsy, contralateral superior oblique weakness becomes unmasked; unfortunately, then, a second surgery is required.

Patients with torsional complaints are among the most difficult to treat. Considerations are as follows:

• In general, patients can fuse up to about 8° of cyclotropia before becoming symptomatic.
• Patients with bilateral fourth nerve palsies from head trauma should be warned about the likelihood of persistent diplopia after surgery.
• Many of these patients also may have central disruption of trauma from severe head injury and will be unable to fuse even after excellent surgical alignment.

• References

Complications

As with any strabismus surgery, undercorrections and overcorrections may occur. It is generally better to undercorrect a patient than to overcorrect a patient.

For patients with long-standing disease and large fusional amplitudes, a small residual deviation may be perfectly well controlled, but an overcorrection will be intolerable.

Adjustable suture surgery minimizes risk of overcorrection and undercorrection.

Perhaps the most troublesome complication is that of iatrogenic Brown syndrome, resulting in severe limitation of elevation.^[38] Assessing superior oblique tendon intraoperatively should make this less likely.

• References

Outcome and Prognosis

Prognosis of trochlear nerve palsy varies depending on etiology. Best information regarding outcome comes from cases collected at the Mayo Clinic over the past 40 years, as follows:

• Rates of complete and spontaneous resolution of microvascular fourth nerve paresis is excellent, with 89% of patients achieving resolution within 10 months.^[39]
• Idiopathic cases also have greater than 50% likelihood of spontaneous recovery.
• Most cases resolve within weeks to months, with the vast majority completely recovering by 6 months.
• Some cases may resolve slowly over the course of a year.
• Patients with head trauma were less likely to recover, yet, 44% of these patients experienced gradual and spontaneous recovery.^[40]
• Cases due to aneurysm or neoplasm were least likely to have functional recovery.

Because patients have good fusional abilities, surgery generally produces excellent results. Wang et al reported an “excellent” surgical outcome in 74% of patients and a “good” surgical outcome in 23% when evaluating degree and pattern of vertical deviation and degree of oblique muscle dysfunction.^[33] Plager reported a nearly 90% success rate with his surgical algorithm.^[32] Mitchell and Parks also reported excellent results in correcting excyclotorsion using modified Harada-Ito procedure.^[35]

• References