Fourth cranial nerve (trochlear nerve) palsy

INTRODUCTION — Paralytic strabismus refers to nonalignment of the eyes and is caused by weakness or paralysis of one or more of the extraocular muscles. Dysfunction of the fourth cranial nerve (trochlear nerve), which innervates the superior oblique muscle, is one cause of paralytic strabismus and can result from lesions anywhere along its path between the fourth nerve nucleus in the midbrain and the superior oblique muscle within the orbit. These lesions can be congenital or acquired.

The manifestations and diagnosis of fourth nerve palsy, also known as superior oblique paralysis and trochlear nerve palsy, are reviewed here. Palsies of the third and sixth cranial nerves are discussed separately. (See "Third cranial nerve (oculomotor nerve) palsy in children" and "Sixth cranial nerve (abducens nerve) palsy".)

ANATOMY — The fourth cranial nerve (trochlear nerve) has the longest intracranial course; it is the only cranial nerve that has a dorsal exit from the brainstem (figure 1). It begins in the midbrain at the level of the inferior colliculus as fascicles extending from the fourth nerve nuclei. The trochlear nerves cross after they exit dorsally in the anterior medullary velum. The fourth nerve passes between the superior cerebellar artery and the posterior cerebral artery and runs in the subarachnoid space. It travels within the lateral wall of the cavernous sinus and enters the orbit via the superior orbital fissure to innervate the superior oblique muscle [1-10].

The fourth cranial nerve is a purely efferent or pure motor nerve and it innervates a single muscle, the superior oblique. The primary action of the superior oblique muscle is intorsion of the eye in the primary position; the secondary action is depression of the eye in the adducted position; a tertiary action of the muscle is abduction (especially in the abducted position) (table 1).

The long course of the fourth cranial nerve renders it particularly prone to injury from blunt head trauma or compression from changes in intracranial pressure, brain tumors, or swelling anywhere along its course.

CLINICAL MANIFESTATIONS — Patients may present with fourth cranial nerve palsy at any age and in either gender. Many case series report a male predominance, presumably because of the greater incidence of trauma in young males [11,12].

Fourth cranial nerve palsy — Individuals with fourth nerve palsies may complain of binocular (ie, present with both eyes open) vertical diplopia and/or subjective tilting of objects (torsional diplopia). Because the superior oblique also depresses the eye in the adducted position, objects viewed in primary position, and especially in down-gaze, may appear double (eg, when going down a flight of stairs). More mildly affected individuals may complain of blurred vision, difficulty focusing, and dizziness rather than overt diplopia.

The patient may adopt a conscious or unconscious head tilt. This is because torsional and vertical diplopia often improve with head tilting to the side opposite the paralyzed muscle (picture 1). As an example, vertical and torsional diplopia in a patient with left fourth nerve palsy improve with the head tilted toward the right. Old photographs may show the long-standing compensatory contralateral head tilt in congenital or long-standing palsies. Additionally, some patients may subconsciously close one eye when reading.

On examination, an ipsilateral hypertropia (deviation upward) and excyclotorsion (rotation outward) of the involved eye is present because the superior oblique muscle intorts and depresses the eye. The upward deviation is greater when gaze is in the direction of action of the weak muscle (downgaze and contralateral horizontal gaze). The deviation is also greater in ipsilateral head tilt. Thus, a left fourth nerve palsy causes a left hypertropia, which is greater in right gaze and with the head tilted to the left. These characteristics form the basis for the diagnosis. (See 'Unilateral fourth nerve palsy' below.)

Patients with only a small angle deviation from a unilateral superior oblique palsy can present with little or no primary position hypertropia and only head tilt test and gaze tests upon examination (ie, the three-step test). In this setting, it is important to consider the possibility of masked bilateral superior oblique palsies (the primary position deviation is obscured because the bilateral fourth nerve palsies cancel each other out). These examinations are described in detail below. (See 'Clinical evaluation and diagnosis' below.)

The direction and degree of subjective torsion can be measured objectively with a double Maddox rod. The affected eye is usually extorted because the superior oblique muscle is an intorter of the eye. (See 'Measurement of torsion' below.)

Associated clinical features — Fourth nerve palsies may be isolated or accompanied by other contributory neurologic abnormalities. Nonisolated palsies may be divided into four syndromes based upon the topographic anatomy of the fourth nerve (table 2) [13]:

●A midbrain nuclear or fascicular lesion (eg, tumor, stroke, demyelination) is typically accompanied by other brainstem symptoms, such as hemisensory loss, hemiparesis, a central Horner syndrome, or other brainstem cranial neuropathies.

●Lesions of the subarachnoid space (eg, meningitis) are typically associated with other signs and symptoms including headache, stiff neck, and other cranial nerve abnormalities. Focal lesions (aneurysms, schwannomas) may produce isolated fourth nerve palsies.

●Cavernous sinus lesions are usually associated with other localizing signs (eg, third, fifth, or sixth nerve dysfunction, or Horner syndrome).

●Orbital apex lesions often involve third, fifth, and sixth cranial nerves as well as the optic nerve. Orbital involvement may also produce such signs as proptosis, chemosis, and orbital or conjunctival edema.

The fourth nerve exits from the dorsum of the brainstem. Thus, neurologic signs of cerebellar disease may be present if a tumor in that region is causing the fourth nerve palsy.

CLINICAL EVALUATION AND DIAGNOSIS — Fourth cranial nerve palsy should be suspected in patients with binocular vertical diplopia and/or subjective tilting of objects (torsional diplopia). The diagnosis can be confirmed using a three-step clinical evaluation as described below.

Unilateral fourth nerve palsy — During gross ductional testing in various directions of gaze, the ocular movements can appear to be full despite weakness of the superior oblique muscle. In some cases, however, the affected eye has reduced infraduction with adduction. The Parks-Bielschowsky three-step test is performed to make the diagnosis of fourth nerve palsy (picture 1 and algorithm 1) [14,15]:

●Step 1 – Which is the higher (hypertropic) eye (picture 1)? (See panel B.)

The determination of the more hypertropic eye narrows the paretic possibilities to four extraocular muscles (the ipsilateral superior oblique or inferior rectus or the contralateral inferior oblique or superior rectus) as in panel B (picture 1). As an example, if the left eye is higher (a left hypertropia), the muscles that are potentially involved include the depressors of the left eye, the left superior oblique, and the left inferior rectus; or the elevators of the right eye, the right inferior oblique, and the right superior rectus.

●Step 2 – Is the hypertropia worse in right or left gaze?

The determination of which horizontal gaze worsens the hypertropia narrows the possible muscles involved from four to two because only two muscles act in right gaze and two in left gaze. The hypertropia is worse in contralateral gaze because that movement is controlled by the paretic muscle, as in panel C (picture 1). Thus, worsening of the hypertropia in right gaze in a patient with left hypertropia implicates either the left superior oblique or the right superior rectus.

●Step 3 – Is the hypertropia worse in right or left head tilt?

The determination of which head tilt worsens the hypertropia (Bielschowsky head tilt test) identifies the involved muscle, as in panel D (picture 1). Hyperdeviation is worse in ipsilateral head tilt in a fourth nerve palsy because the intorsion ability of the ipsilateral superior oblique is weak and is compensated for by the other ipsilateral intorter (the superior rectus). Activation of the superior rectus causes elevation of the eye and increases the hypertropia. The deviation improves in contralateral head tilt, the position that typically is adopted by the patient to reduce diplopia. Thus, left hypertropia that worsens with right gaze and left head tilt is consistent with a left superior oblique (or fourth nerve) palsy.

Inconsistencies in these findings suggest that there is not an isolated fourth nerve palsy and that other diagnoses should be considered (algorithm 1). (See 'Differential diagnosis' below and "Overview of diplopia".)

The best time to diagnose a fourth nerve palsy is early in its course. If the palsy does not resolve, there is a tendency for the deviation to become more "comitant." This means the hypertropia that was once limited largely to one field of gaze will creep into the opposite field due to the contraction, and thus overaction, of the antagonistic muscle [16].

Some authors advocate for a "fourth step" to ensure that the typical excyclotorsion of a weak superior oblique muscle is present on the affected side using double Maddox rod or fundus photography (demonstrating the ipsilateral excyclotorsion). The upright-supine test is an alternative proposed fourth step to differentiate skew deviation from other causes of vertical strabismus. (See 'Ocular tilt reaction and skew deviation' below.)

The exam can be limited in noncooperative patients. Therefore, if head tilt is present and the three-step test is unable to be performed, some ophthalmologists patch one eye and look for resolution of tilt [17].

Bilateral fourth nerve palsies — Bilateral fourth nerve palsies are suggested by the following features (picture 2):

●Alternating hypertropia on horizontal gaze or head tilt (eg, right hypertropia in left gaze and left hypertropia in right gaze).

●Positive head tilt test to either shoulder (double Bielschowsky head tilt test).

●Large degree of excyclotorsion (>10 degrees).

●V-pattern esotropia (ie, a difference of 15 prism diopters or more in esotropia between upward and downward gaze) caused by a decrease in the abducting effect of the superior oblique(s) in depression and overaction of the inferior oblique muscle(s).

●Underaction of both superior oblique muscles and/or overaction of both inferior oblique muscles.

●A relatively small hypertropia in primary position (the two eyes have a vertical deviation and tend to cancel each other out).

These clinical features should be used in combination to diagnose bilateral fourth palsy. Individual tests (eg, alternating hypertropia, head tilt) are insufficiently sensitive to be used in isolation [18].

Measurement of torsion — Torsion is measured objectively with a double Maddox rod. It is important to measure torsion because significant torsion (>5 to 8 degrees) may require torsion surgery (eg, the Harada-Ito procedure). In addition, the torsion may be a limiting factor for fusion even if the vertical and horizontal deviations are corrected surgically or with prism.

DIFFERENTIAL DIAGNOSIS — Other conditions can present with similar findings and should be considered, particularly when the patient does not meet criteria for fourth nerve palsy. (See 'Unilateral fourth nerve palsy' above.)

Restrictive vertical strabismus — Restrictive vertical strabismus can be produced by orbital floor fracture, orbital tumors, orbital pseudotumor, and Graves ophthalmopathy. Patients with these conditions usually have additional orbital signs, such as proptosis, chemosis, and conjunctival injection. Forced ductions (passive rotation of the eyes with ophthalmic forceps) typically confirm the restrictive nature of the ophthalmoplegia. (See "Clinical features and diagnosis of thyroid eye disease".)

Other paretic vertical strabismus — Paretic vertical strabismus can be produced by a partial third nerve palsy that affects the inferior rectus, superior rectus, or inferior oblique. Other features of third nerve palsy (eg, ptosis, deficits in adduction, elevation, and/or depression) demonstrated on examination help to differentiate third from fourth nerve palsy. (See "Third cranial nerve (oculomotor nerve) palsy in children" and "Third cranial nerve (oculomotor nerve) palsy in adults".)

Myasthenia gravis — Myasthenia gravis can mimic any painless, pupil-spared, nonproptotic ophthalmoplegia [19]. Other signs of myasthenia gravis, such as ptosis, variability, and fatigue, are usually present. (See "Ocular myasthenia gravis", section on 'Clinical features'.)

Ocular tilt reaction and skew deviation — Ocular tilt reaction and skew deviation are vertical misalignments caused by disruption of vestibulo-ocular connections. Similar to fourth nerve palsy, skew deviation presents with vertical misalignment, cyclotorsion, and head tilt [20,21]. In skew deviation, the pattern of vertical misalignment does not follow a set pattern with gaze direction or head tilt, but may mimic a fourth nerve palsy. However, as measured by double Maddox rod, the laterality and direction of torsion in skew deviation (bilateral rather than unilateral torsion or incyclotorsion rather than excyclotorsion) are often inconsistent with superior oblique paralysis. In the uncooperative patient, a photograph of the fundus can be taken to demonstrate the torsion; in skew deviation, the fundus of the hypertropic eye is typically incyclotorted, while in fourth nerve palsy the fundus is excyclotorted.

In addition, ocular torsion and vertical misalignment are position dependent in skew deviation (decreasing with position change from upright to supine), whereas they are relatively unaffected by position in fourth nerve palsy [22,23]. A positive upright-supine test (vertical strabismus decreases by ≥50 percent with position change from upright to supine) suggests skew deviation with high specificity in one series [23].

Finally, skew deviation typically is accompanied by other posterior fossa signs (eg, other cranial neuropathies, hemisensory loss, or hemiparesis) and more widespread brainstem disease. (See "Ocular gaze disorders", section on 'Skew deviation'.)

Thyroid ophthalmopathy — Thyroid ophthalmopathy is more commonly seen in adults. (See "Clinical features and diagnosis of thyroid eye disease".)

ETIOLOGIC EVALUATION

Causes of isolated fourth nerve palsy — Most isolated fourth nerve palsies are congenital, even those presenting in adulthood. The most common causes of acquired lesions are trauma and microvascular disease [11,24-26].

Congenital — In most series, the most common causes of fourth nerve palsies in both children and adults are congenital (33 to 50 percent) [11,24-28]. Differentiating acquired fourth nerve palsy from decompensation of a congenital fourth nerve palsy is important because patients with isolated congenital palsies do not typically require further neurologic evaluation or imaging.

Patients with congenital fourth nerve palsy are often able to compensate for the double vision with a head tilt that minimizes symptoms (picture 1). Over time, many patients with congenital fourth nerve palsy have increasing difficulty controlling the symptoms and may present with diplopia. They may insist that this is a new problem, although old photos frequently demonstrate a long-standing head tilt [14].

A peculiar feature of congenital fourth nerve palsy is that the amount of hypertropia in the primary position is very large (deviations as high as 20 or 30 prism diopters). A true acquired fourth nerve palsy of recent onset will have a hypertropia that measures prism diopters in the mid-teens in the primary position at the most [29].

The following additional features may be present in patients with congenital fourth nerve palsies:

●Lack of complaints of cyclotropia (subjective image tilting), despite objective fundus excyclotorsion.

●Ability to fuse relatively large vertical deviation of the eyes (ie, large vertical fusional amplitudes measuring greater than 6 to 8 prism diopters). In some cases of congenital fourth nerve palsy, the amount of hypertropia may be as high as 20 or 30 prism diopters.

●Facial asymmetry (hypoplasia of the face on the side of head turn) in long-standing or congenital palsies.

The amount of hypertropia may not match the degree of head tilt in fourth nerve palsy for a number of reasons:

●The head tilt generally compensates for the torsion, but not necessarily the vertical deviation, and some patients may even tilt in the opposite direction to better suppress or ignore the second image.

●Variable amounts of sensory cyclofusion exist in patients, which can obscure or negate the torsion that is seen objectively.

●Some patients tilt their heads to create disparity in the image rather than relieve the deviation (and thus can even be tilting their head in the wrong direction).

While familial fourth nerve palsy is rare, congenital fourth nerve palsy has been reported in multiple families [30,31]. The pedigree analysis of five affected members in one family indicated an autosomal dominant inheritance pattern [31].

While magnetic resonance imaging (MRI) is not required to evaluate patients with congenital fourth nerve palsy, corroborative findings may include absent or atrophic superior oblique muscle; comparison with the unaffected side may be required as the findings may be subtle [32].

In one series of isolated fourth nerve palsy, the degree and direction of horizontal eye deviation differed between congenital and microvascular causes; in congenital lesions, exotropia (outward deviation) was most common, occurring in 86 percent, while in microvascular lesions, esotropia and horizontal orthophoria occurred in 29 and 34 percent, respectively [27]. The clinical utility of this observation is uncertain.

Traumatic — Traumatic fourth nerve palsies, in contrast to traumatic third and sixth nerve palsies, may occur with a relatively mild blow to the head (ie, not associated with loss of consciousness or a skull fracture) [33,34].

Bilateral involvement occurs in a significant minority of patients with traumatic fourth nerve palsy. In one series of 270 patients with superior oblique paralysis, one-fourth of cases caused by trauma had bilateral involvement [24]. Careful examination for bilateral fourth nerve palsies is necessary; the palsies may be asymmetric. It is unfortunate for a surgeon to have corrected a fourth nerve palsy by weakening the ipsilateral inferior oblique muscle, only to find a contralateral fourth nerve palsy now uncovered and obvious to the patient [26,35,36]. (See 'Bilateral fourth nerve palsies' above.)

In most cases, MRI is unremarkable, implicating an injury to the nerve itself; however, in some patients, a dorsal midbrain contusion or hemorrhage is documented [37].

Some traumatic fourth nerve palsies improve with time, but most do not.

Microvascular disease — While more commonly affecting the third and sixth cranial nerves, microvascular disease can involve the fourth cranial nerve as well [27,38-41]. In one series, microvascular disease related to hypertension and/or diabetes was believed to underlie 24 percent of cases [11].

Such patients are typically older with microvascular risk factors (hypertension, diabetes) and usually present with an abrupt onset of symptoms [39,42]. MRI may show an infarction in the tegmentum of the midbrain, affecting the fascicle of the fourth nerve. While microvascular infarction of the fourth nerve presumably also occurs, these are not demonstrable on MRI and the diagnosis is presumptive rather than confirmed.

Idiopathic — A minority of patients with trochlear nerve palsy have no etiologic diagnosis after evaluation (3 of 75 patients or 4 percent in one of the largest more recent series) [11]. Idiopathic fourth nerve palsies, like idiopathic third and sixth nerve palsies, often present with mild discomfort or pain over the eyebrow of the affected eye that stops shortly after the diplopia starts [2,3,24,43,44]. When asked to point to the pain, patients usually indicate an area just above the brow on the side of the muscle weakness. Rarely does the pain require medication.

The idiopathic cases may resolve in a few weeks, and some authors defer additional neuroradiologic testing until two months have passed without improvement as long as the other cranial nerves are normal [5,45].

Other — Less common causes of isolated fourth nerve palsies include tumors of the brainstem or along the course of the fourth nerve (eg, schwannoma [46-50], cavernous hemangioma [40], metastasis [51]), intracranial or meningeal infections [52-54], zoster ophthalmicus [11,12,16], pituitary macroadenoma [55,56], intracavernous or superior cerebellar artery aneurysm [57,58], and perimesencephalic subarachnoid hemorrhage [59].

Rarely, a fourth nerve palsy can be due to raised intracranial pressure [60,61]. It is important to look carefully at the optic nerve head to be sure that there is no papilledema.

Causes of nonisolated fourth nerve palsy — These are categorized according the anatomic location of involvement as listed in the table (table 2) [13].

Radiologic evaluation — Individuals who have nonisolated fourth nerve palsies with neurologic signs or symptoms that localize to the brainstem, subarachnoid space, cavernous sinus, or orbit should undergo neuroimaging to best evaluate the localized area (table 2). Patients with a neurologically isolated fourth nerve palsy that seems clearly congenital, traumatic, or ischemic do not require neuroimaging; however, corroborative findings on neuroimaging are sometimes seen for these conditions. (See 'Congenital' above and 'Traumatic' above and 'Microvascular disease' above.)

MRI is superior to computed tomography (CT) scan for the evaluation of a nonisolated fourth nerve palsy. MRI is more sensitive in the detection of intracranial lesions in the posterior fossa and is not susceptible to the bone artifacts that are seen with CT scanning. CT scanning should be used in patients who require evaluation of bone or acute bleeding, or who cannot undergo an MRI.

In addition to detecting causative lesions in the midbrain, cavernous sinus, and orbit, MRI may demonstrate enhancing nerve lesions in the subarachnoid space that may represent schwannoma or focal inflammation [48,49].

Additional evaluation — Lumbar puncture may be warranted in patients who have normal imaging studies but are suspected of having a meningitic (subarachnoid space) process. (See 'Associated clinical features' above.)

Evaluation for mimics (eg, myasthenia gravis, thyroid eye disease, skew deviation) may be warranted depending on the clinical presentation, but typically, an isolated fourth nerve palsy is a relatively straightforward clinical diagnosis. (See 'Differential diagnosis' above.)

TREATMENT AND PROGNOSIS — Treatment of the underlying etiology in patients with acquired nontraumatic fourth nerve palsy (eg, brain tumor, increased intracranial pressure) may alleviate the diplopia.

Symptomatic patients with isolated palsies that are congenital or traumatic should be considered for treatment. The goal of treatment is to maximize visual function, including ocular alignment.

Microvascular lesions are likely to improve and resolve over weeks to months [12,27]. Patients with traumatic fourth nerve palsy, depending upon the severity of the injury to the nerve, may improve over time and often are observed for several months before being considered for treatment. If the palsy does not resolve, the tendency is for it to become comitant, making it suitable for prism therapy. Comitant deviations are those in which the distance between the double images is equal in the various gaze directions and symptoms are only slightly affected by the direction of gaze.

Prism therapy may be employed for small, comitant, long-standing deviations [28]. A temporary press-on (Fresnel) prism of sufficient power to align the eyes is placed on the spectacle lens. Permanent prisms can be ground into the spectacle lens if the patient is happy with the result and the deviation fails to improve spontaneously. Strabismus surgery may be helpful in patients who fail prism therapy.

Patching one eye will alleviate binocular diplopia and is useful for patients who are being observed or who defer prism or surgical therapy. Patching should be employed with caution and with the assistance of an ophthalmology consultant in children in the amblyopic age range. (See "Amblyopia in children: Classification, screening, and evaluation", section on 'Definition'.)

Additional therapies may alleviate the symptoms of traumatic fourth nerve palsy while it recovers its function (ie, botulinum toxin injection in the inferior oblique muscle) [62]. Galantamine has been proposed in traumatic trochlear nerve palsy, but anecdotal reports of efficacy require independent confirmation [63].

SUMMARY AND RECOMMENDATIONS

●The fourth cranial nerve (trochlear nerve) supplies the superior oblique muscle. The actions of the superior oblique muscle include intorsion, depression, and abduction (table 1). (See 'Anatomy' above.)

●Clinical manifestations of fourth nerve palsy include vertical diplopia, torsional diplopia, extorsion, head tilt (to avoid diplopia), and ipsilateral hypertropia (elevation of the affected eye). (See 'Clinical manifestations' above.)

●Fourth nerve palsies can be classified as isolated or nonisolated (ie, accompanied by other neurologic abnormalities). Nonisolated palsies produce symptoms according to the topographic anatomy of the fourth nerve (table 2). (See 'Associated clinical features' above.)

●Unilateral fourth nerve palsy is diagnosed using the three-step test (picture 1 and algorithm 1). (See 'Unilateral fourth nerve palsy' above.)

●Bilateral fourth nerve palsies are suggested by alternating hypertropia on horizontal gaze, positive head tilt test to either shoulder, excyclotorsion >10 degrees, V-pattern esotropia, underaction of both superior oblique muscles and/or overaction of both inferior oblique muscles, and a relatively small hypertropia in primary position. (See 'Bilateral fourth nerve palsies' above.)

●The differential diagnosis of fourth nerve palsy includes childhood strabismus, myasthenia gravis, ocular tilt reaction and skew deviation, and thyroid ophthalmopathy. These can usually be distinguished on careful examination as described. (See 'Differential diagnosis' above.)

●The most common causes of fourth nerve palsies are congenital, traumatic, and microvascular. (See 'Causes of isolated fourth nerve palsy' above.)

●Patients with isolated fourth nerve palsy with a clearly defined etiology that is congenital, traumatic, or microvascular do not require further imaging, although corroborative findings may be identified in such cases.

Individuals with nonisolated fourth nerve palsies (neurologic signs or symptoms that localize to the brainstem, subarachnoid space, cavernous sinus, or orbit) should undergo brain imaging, usually with contrast-enhanced magnetic resonance imaging (MRI) to best evaluate the localized area (table 2). (See 'Radiologic evaluation' above.)

●Lumbar puncture may be warranted in patients who have normal imaging studies but are suspected of having subarachnoid space lesions. (See 'Additional evaluation' above.)

●Treatment for fourth nerve palsy is directed at the underlying etiology. The goal of other therapies is to maximize visual function, including ocular alignment. (See 'Treatment and prognosis' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Claudia Prospero Ponce, MD, and Aroucha Vickers, MD, who contributed to an earlier version of this topic review.