Abstract and Introduction

Abstract

The diagnosis and etiologies of sixth cranial nerve palsies are reviewed along with nonsurgical and surgical treatment approaches. Surgical options depend on the function of the paretic muscle, the field of greatest symptoms, and the likelihood of inducing diplopia in additional fields by a given procedure. (Comp Ophthalmol Update 7: 215-21, 2006)

Introduction

Sixth cranial nerve (abducens) palsy is a common cause of acquired horizontal diplopia. Signs pointing toward the diagnosis are an abduction deficit and an esotropia increasing with gaze toward the side of the deficit (Figure 1). The diplopia is typically worse at distance. Measurements are made with the uninvolved eye fixing (primary deviation), and will be larger with the involved eye fixing (secondary deviation). A small vertical deficit may accompany a sixth nerve palsy, but a deviation over 4 prism diopters should raise the question of additional pathology, such as a fourth cranial nerve palsy or skew deviation.^[1]

Figure 1. 

Patient with a microvascular right sixth nerve palsy. Note the lack of abduction of the right eye.

In a recent population-based study that reviewed 137 patients spanning a 15-year period, the sex incidence was equal, the annual incidence was 11.3/100,000, and the peak incidence was in the seventh decade. In 35% of the cases, the patients had hypertension and/or, less frequently, diabetes; 26% were undetermined, 5% had a neoplasm, and 2% had an aneurysm. It was noted that patients who had an aneurysm or neoplasm had additional neurologic signs or symptoms or were known to have a cancer.^[2]

Anatomical Considerations

The sixth cranial nerve nuclei are located in the lower pons beneath the fourth ventricle. The nerve on each side exits from the ventral surface of the pons. It passes from the posterior cranial fossa to the middle cranial fossa, ascends the clivus, and passes under the petro-clinoid ligament in Dorello's canal. It then enters the cavernous sinus where, unlike its fellow cranial nerves, it is unsupported by the dural wall of the sinus. It passes through the superior orbital fissure and into the orbit through the annular ligament of the rectus muscles, and then to the lateral rectus.

Although shorter in length than the fourth cranial nerve, the course of the sixth nerve leaves it vulnerable to a variety of insults.^[3] Lesions in the pons may be associated with internuclear ophthalmoplegia, ipsilateral horizontal gaze palsy, and contralateral long tract signs (weakness), as well as the possible involvement of cranial nerves V, VII, and VIII ( Table 1 ). After exiting the pons, the nerve is susceptible to increases in intracranial pressure from a variety of causes. Petrous bone trauma or inflammation may be associated with decreased hearing, facial pain, numbness, or hemotympanum. Cavernous sinus lesions or superior orbital fissure lesions are highlighted by fellow cranial nerve palsies or Horner syndrome (Figure 2). A sixth nerve palsy with proptosis and conjunctival inflammation points toward an orbital process.^[4,5]

Figure 2. 

Patient with a right carotid artery aneurysm in the cavernous sinus causing a right sixth nerve palsy with a right Horner syndrome. Note the lack of abduction of the right eye, miosis, and ptosis.

Clinical Considerations

An isolated sixth nerve palsy (no additional neurologic or ocular signs) is a common presentation ( Table 2 ). Traditionally, adults over 50 years of age presenting with isolated sixth nerve palsy and with vasculopathic risk factors (diabetes, hypertension) may be observed without imaging for 3 months, as a microvascular etiology is common. Warwar recently presented a case of a 68-year-old man with vasculopathic risks who presented with an isolated sixth nerve palsy secondary to pituitary apoplexy.^[6] The patient developed a third cranial nerve palsy a few days after presentation, went into cardiac arrest, and died. The author recommended that neuroimaging be considered in patients with isolated sixth nerve palsy, even in the presence of a strong vasculopathic history.

A prospective study of 43 patients (ages 2–82, mean age = 48) with isolated sixth nerve palsies by Bendszus identified 63% with lesions considered relevant to the palsy on MRI.^[7] Of these patients, 49% had tumor or tumor-like lesions. Repeat MRI at 3–6 months was normal in all patients with initial normal MRIs. The authors recommended MRI in all patients presenting with acute sixth nerve palsy, even with a vasculopathic history.

Patel, in a study of 76 patients with isolated nontraumatic sixth nerve palsy without a suspected systemic etiology other than microvascular, found a strong association with both diabetes and coexistent diabetes and hypertension, but not with hypertension alone.^[8] Scott reviewed the long-term outcome of 59 patients with vasculopathic sixth nerve palsy and reported that 86% had complete resolution of the palsy, and that five of eight patients with incomplete resolution were asymptomatic. He cautioned, however, that almost one-third of these patients had at least one recurrent episode.^[9] An MRI should be performed in younger adults with isolated sixth nerve palsy, and in all patients with sixth nerve palsy accompanied by additional cranial nerve or other neurologic findings. The studies by Warwar and Bendszus raise controversy about whether to image all patients with acute sixth nerve palsy.

Patients with bilateral or nonisolated sixth nerve palsy should have an MRI, medical work-up, and lumbar puncture. Accompanying neurologic deficits may point toward areas of the brain to focus on as discussed above. Infectious etiologies, such as botulism or cytomegalovirus (CMV), neoplasm (nasopharyngeal cancer), or inflammatory causes, such as Guillain-Barre syndrome, should be kept in mind.^[10]

Pain with a sixth nerve palsy is nonspecific. A microvascular sixth nerve palsy may or may not be accompanied by pain. An inflammatory etiology, such as Tolosa-Hunt syndrome, is painful and typically responds quickly to steroids. Other etiologic considerations would include aneurysm, bone metastasis, and ophthalmoplegic migraine.

A child may develop a sixth nerve palsy following a viral illness, and the role of MRI in children with isolated sixth nerve palsy is controversial. Neuroimaging is recommended in a child with persistent, bilateral, or sixth nerve palsy accompanied by other neurologic signs or symptoms. At a tertiary referral center, Lee found neoplasm or neoplasm-related surgery to be the most common etiology of sixth nerve palsy in 75 children.^[11] In contrast, Holmes, in a population-based study of cranial nerve palsies in children, found no cases of neoplasia with isolated palsies.^[12]

A sixth nerve palsy secondary to chronic middle ear infections and mastoiditis is less commonly seen with current antibiotics and immunizations. Pseudotumor cerebri can be seen in children, and may be accompanied by a sixth nerve palsy. Duane and Mobius syndromes have abduction defects, but the deficits are associated with other signs (palpebral fissure narrowing in the former, facial paresis in the latter). Trauma, unfortunately, continues to be a frequent cause of sixth nerve palsies in children ( Table 2 and Table 3 ).

Differential Diagnosis

An abduction deficit may be secondary to poor function due to cranial nerve palsy, mechanical restriction, a disease process affecting muscular function, or a congenital disorder ( Table 4 ). Restriction of the medial rectus may be the direct result of medial orbital wall trauma, and a "tight" medial rectus may occur with time with any palsy of the lateral rectus. Thyroid eye disease and orbital inflammatory disease may result in restriction of extraocular muscles, but are typically accompanied by characteristic signs and symptoms, such as proptosis, injection over the rectus muscle insertions, lid retraction, and lid lag. Forced duction testing may be helpful to rule out a restrictive etiology for an abduction deficit.

Myasthenia gravis is always an etiologic consideration with the acute onset of strabismus. A history of variability is a red flag for this diagnosis. The ice test and rest test are useful office procedures to look for functional improvement in patients with myasthenia. The acetylcholine receptor antibody test is negative in nearly half of patients with solely ocular myasthenia. Tensilon testing may give a falsenegative result, and repeat testing may be needed if the test is negative and clinical suspicion is high. Single muscle fiber electromyography (EMG) may be the best test for a definitive diagnosis of myasthenia. It is very sensitive; however, it is not specific for myasthenia.^[13]

Spasm of the near reflex can simulate an abduction deficit. The convergence is associated with miotic pupils, and ductions are full with one eye occluded.

Divergence paresis or divergence insufficiency with a comitant esodeviation greater at distance than near (or none at near), and with decreased divergence fusional amplitudes can also simulate a sixth nerve weakness. Divergence paresis has little localizing value. There is controversy about whether these patients should have an MRI.^[14]

Nonsurgical Treatment

Nonsurgical approaches include patching to avoid diplopia, prisms, botulinum toxin (Botox® [Allergan, Inc., Irvine, CA]) injection of the ipsilateral medial rectus, and steroids if the etiology is inflammatory. The patient should be followed regularly to observe for improvement or worsening of the deviation. A worsening deviation may indicate ipsilateral medial rectus contraction, and would be an indication for a work-up to rule out a progressive lesion.

Patching is an effective way to temporarily relieve symptoms of diplopia, and can be accomplished with a standard eye patch or with the use of opaque tape on the patient's spectacles. Patching the palsied eye is generally more comfortable for the patient to decrease past-pointing and disorientation

Prisms are often not effective due to the incomitance of the deviation, but can be tried for small deviations or postoperatively if needed. A trial with a Fresnel Press On Prism (The Fresnel Prism and Lens Co., LLC, Eden Prairie, MN) is an inexpensive way to see if a prism is effective and tolerated, and allows simple power adjustments.

The role of Botox® for acute sixth nerve palsy remains unsettled (Figure 3). It has been used to attempt to prevent or reduce the contracture of the antagonist medial rectus, and also to treat small postoperative deviations. The known occurrence of spontaneous recovery of some sixth nerve palsies clouds the interpretation of case-report studies. Reports sometimes include various etiologies, both traumatic and nontraumatic, lumped together. Hung reported a higher functional recovery rate in a retrospective study in 14 of 33 patients with acute complete traumatic sixth nerve palsies who were treated with Botox®.^[15] Holmes reviewed the course of 84 patients with traumatic sixth nerve palsies, 22 of whom were treated with Botox® and the remainder treated conservatively. He found no difference in the outcome of the patients.^[16] Biglan reported that 7 of 16 patients with sixth nerve palsy were controlled by Botox®, and that patients with long-standing or severe palsy did not get as positive a result as patients with more acute palsies or with better lateral rectus function.^[17] In a study of nine children with brain neoplasms accompanied by sixth nerve palsies, treatment with Botox® was not felt to hasten recovery.^[18] Eight patients with nontraumatic sixth nerve palsies were reported to have excellent results from Botox®, with seven having no diplopia in the long term.^[19] Complications of Botox® included ptosis, induced hypertropia, subconjunctival hemorrhage, possible globe perforation, and failure to maintain an effect.

Figure 3. 

Top: Patient with left sixth nerve palsy. Bottom: 2 weeks after botulinum toxin was injected into the left medial rectus. Note the decreased adduction and the increased abduction of the left eye from the botulinum toxin.

Surgical Treatment

Surgical approaches are based on the function of the paretic muscle, the field(s) of diplopic symptoms, and the likely secondary effects of a procedure. Surgical procedures are generally considered at the 6-month time frame, since most sixth nerve palsies that improve will have recovered by that time. If the palsy continues to improve, it may be observed. Surgical choices depend on the degree of residual lateral rectus function as well as the direction of deviation ( Table 5 ). Function is most frequently graded by observation. The forced duction test is helpful to judge the degree of mechanical restriction. The force generation test can help judge the strength of muscle action in cooperative patients. It is accomplished by fixating the eye with forceps or a cotton swab and asking the patient to look in a given direction in order to judge the strength of the muscle's movement. Saccadic velocity may be formally tested with electrooculography if available, but this is rarely done clinically. Mild functional impairment is marked by only slightly decreased motion in the field of greatest action of the muscle; moderate functional impairment has a 50% to 75% decrease in action; and severe impairment has no function of the muscle. Scott graded lateral rectus function as poor, fair, or good based on force generation testing; medial rectus contraction based on a 0 to +3 scale of forced duction testing; and active ductions on a 0 (normal) to –5 (not able to rotate the eye from the opposite field to the midline) scale.^[20]

Mild lateral rectus paresis may be addressed by a recession of the ipsilateral medial rectus, or by a recession of the yoke contralateral medial rectus (creating a matching weakness in the contralateral eye [Figure 4]), which would be less likely to induce an exotropia in contralateral gaze. A contralateral medial rectus posterior fixation suture (Faden operation) may also effectively serve this purpose. In a moderate paresis, it is usually necessary to resect the paretic lateral rectus and recess either the antagonist or yoke medial rectus. The same considerations apply about trying to avoid creating an exotropia in contralateral gaze. A contralateral medial rectus posterior fixation suture may be helpful in more severe palsies to expand the field of single binocular vision. In severe sixth nerve palsy with no lateral rectus function, a transposition procedure plus a weakening of the contralateral medial rectus is indicated (Figure 5). If forced ductions reveal a contracted ipsilateral medial rectus, either Botox® at the time of surgery or a recession of the tight medial rectus as a second procedure to decrease the chance of anterior segment ischemia may be considered. The reader is referred to standard texts for details of surgical procedures.

Figure 4. 

Top: Patient with a mild right sixth nerve palsy. Bottom: Postoperative photograph after a left medial rectus Faden operation.

Figure 5. 

Top: Patient with a complete right sixth nerve palsy. Bottom: Postoperative photograph after a transposition of the right superior and inferior rectus to the lateral rectus insertion.

In a multicenter prospective study, Holmes reviewed 33 patients with acute traumatic sixth nerve palsy and found an overall spontaneous recovery rate of 73%. Recovery was higher with unilateral deficits and with better initial muscle function.^[21] In a similar study of 31 patients with chronic sixth nerve palsy of multiple causes (approximately one-third traumatic), 75% were reported to have an eventual surgical success rate.^[22] Of the patients, 10 required second surgeries, and only two of these were considered failures. The success rate for patients with either traumatic or nontraumatic sixth nerve palsy is favorable, particularly for those with residual lateral rectus function. If surgery is indicated, the patient should be aware that more than one procedure may be needed, and prisms may be required postoperatively.

This article was supported in part by a grant from the Research to Prevent Blindness Foundation, New York, NY.

Edward G. Buckley, MD, Duke University Eye Center, Box 3802, Durham, NC 27710 email: buckl002@mc.duke.edu