Tutorial
Introduction
Anatomy
Clinical Manifestations
Evaluation
Bilateral Fourth Nerve Palsy
Differential Diagnosis
Treatment
Bibliography

Isolated Fourth Nerve Palsy

Andrew G. Lee, MD

Introduction

A fourth nerve palsy is a relatively common cause for binocular diplopia in adults. History and examination are necessary to differentiate the common and benign etiologies from the potentially dangerous neurologic causes or mimics (e.g., skew deviation or ocular tilt reaction).

Anatomy

The fourth nerve nucleus resides in the dorsal midbrain. The nucleus supplies the contralateral fourth nerve. The fourth nerve is the only cranial nerve to exit dorsally and has a long intracranial course. The nerve travels ventrally in the subarachnoid space and enters the lateral wall of the cavernous sinus. It then enters the orbit through the superior orbital fissure.

Clinical Manifestations

Typically, patients with fourth nerve palsy have binocular vertical diplopia and may have subjective (tilted environment) or objective evidence of torsion. An incomitant ipsilateral hypertropia is often present. The three-step test is a useful clinical maneuver to establish the diagnosis:

• Determine which is the hypertropic (higher) eye.
• Is the hypertropia worse in the right or left gaze?
• Is the hypertropia worse in the right or left head tilt?

In a fourth nerve palsy, the ipsilateral eye is hypertropic because the superior oblique muscle is a depressor. The hypertropia is worse in contralateral gaze because the misalignment is worse in the gaze direction of the weak superior oblique muscle. The hyperdeviation is worse in ipsilateral head tilt because the incyclotorsion function of the ipsilateral eye is compromised by the weak superior oblique muscle.

The hypertropia increases in ipsilateral head tilt because the incyclotorsion deficit in a superior oblique palsy must be compensated by the other ipsilateral intorter, the superior rectus muscle. The compensatory superior rectus firing increases the hypertropia during the head tilt test. A hypotropia may occur in the normal eye if the affected (paretic) eye is fixating.

Evaluation

Patients with a fourth nerve palsy may be neurologically isolated or associated with other findings (non-isolated). Patients with non-isolated fourth nerve palsy should undergo neuroimaging directed at the topographically localizing findings (e.g., brainstem, fascicle, subarachnoid space, cavernous sinus, superior orbital fissure, or orbit) (Table 1).

A midbrain (nuclear or fascicular) lesion is typically accompanied by brainstem signs (e.g., hemisensory loss, hemiparesis, a contralateral relative afferent pupillary defect, a central Horner syndrome, or other brainstem cranial neuropathies).

Neuroimaging should be directed to the midbrain. Patients with subarachnoid space lesions also have associated signs and symptoms (such as headache, stiff neck, and other cranial neuropathies). Neuroimaging should be directed to the brainstem and subarachnoid space.

Lumbar puncture should follow negative neuroimaging in patients with meningeal signs. Cavernous sinus lesions are usually associated with other localizing signs (e.g., third, fifth, or sixth nerve paresis or Horner syndrome). Neuroimaging should be directed at the cavernous sinus in these patients.

Orbital lesions produce signs such as proptosis, chemosis, and orbital or conjunctival edema. Neuroimaging should be directed to the orbit.

The evaluation of isolated fourth nerve palsies is determined by the clinical setting. Traumatic and congenital palsies do not require additional neuroimaging or further evaluation. Fourth nerve palsies caused by ischemia to the subarachnoid segment (vasculopathic) do not require any initial neuroimaging studies. They may be observed for improvement over the following 6 to 8 weeks.

Spontaneous recovery occurs within 12 weeks in more than 95% of patients. Patients with progressive or unresolved palsies, or those with new neurologic signs or symptoms, should undergo neuroimaging.

Elderly patients with diplopia and headache, scalp tenderness, jaw claudication, or visual loss should undergo an appropriate evaluation for giant cell arteritis (e.g., erythrocyte sedimentation rate and a temporal artery biopsy). Variability or fatigable diplopia or ptosis should be evaluated for myasthenia gravis (e.g., Tensilon test, anti-acetylcholine receptor antibodies).

Patients without vasculopathic risk factors (e.g., hypertension, diabetes, smoking, elevated cholesterol) may require initial neuroimaging, but observation for spontaneous improvement is also reasonable. Coppeto and Lessell reported 12 idiopathic cases that resolved by 4 months. Nemet and colleagues reported 13 patients who resolved by 10 weeks.

Isolated fourth nerve palsies rarely have an underlying intracranial etiology although pituitary adenoma or other compressive lesions have been reported. Patients who do not improve within 2 months should be considered for neuroimaging. Unlike the isolated third nerve palsy, cerebral angiography is not recommended for evaluation for fourth nerve palsy unless an aneurysm is suggested by other neuroimaging studies.

Bilateral Fourth Nerve Palsy

Bilateral non-traumatic fourth nerve palsies should have a neuroimaging study directed at the dorsal midbrain. The clinical features suggesting the diagnosis include:

• An alternating hypertropia on horizontal gaze (e.g., right hypertropia in left gaze and left hypertropia in right gaze)
• Positive head tilt test to either shoulder (double Bielschowsky test)
• Large degree of excyclotorsion (greater than 10º) on double Maddox rod testing
• "V-pattern" esotropia (e.g., secondary bilateral overaction of the inferior oblique muscles)
• Ductional deficit of both of the superior oblique muscles and overaction of inferior oblique muscles
A relatively small hypertropia in primary position (the hypertropia in both eyes cancels out the primary deviation)

Differential Diagnosis

The differential diagnosis for a fourth nerve palsy includes myogenic or restrictive vertical strabismus (e.g., orbital floor fracture, orbital tumor, or orbital inflammatory pseudotumor, thyroid ophthalmopathy), neuromuscular junction (e.g., myasthenia gravis), third nerve palsy, or skew deviation.

Treatment

Patients with diplopia may be treated with patching, prism therapy, or strabismus surgery. Any underlying etiology for the fourth nerve palsy should be treated, if possible. Generally, strabismus surgery is reserved for patients with stable deviations who have failed prism treatment.

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