Third Nerve Palsy (Oculomotor Nerve Palsy) Clinical Presentation

Updated: Oct 08, 2018
  • Author: James Goodwin, MD; Chief Editor: Andrew G Lee, MD  more...
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The following symptoms are encountered with lesions producing third cranial nerve dysfunction:

  • The most common lesions to affect the third cranial nerve involve the peripheral nerve or fascicular portion of the nerve at some level. The symptoms reflect reduced function in the muscles innervated by the nerve, usually in combination; isolated involvement of one or another muscle from nuclear or fascicular third cranial nerve lesions is very rare. The prime symptom is mixed horizontal and vertical binocular diplopia.
  • Ptosis may be partial or complete. Nuclear lesions that spare the central caudate subnucleus to the levator palpebrae superioris may produce third nerve palsies without ptosis. If the ptosis is sufficient to cover the pupil, the patient may complain that he or she cannot see from the eye on the involved side or may not have diplopia because the ptosis is acting as an “occluder.”
  • Ipsilateral pupil mydriasis, anisocoria, and lack of light/near reaction produces little in the way of symptoms, although there may be some glare sensation and photo aversion in bright light.

Neurologic symptoms

Neurologic symptoms associated with lesions involving various portions of the third cranial nerve include those discussed below.

Nuclear portion

Most of the lesions causing nuclear third cranial nerve palsy are due to dorsal midbrain infarction and commonly result in bilateral ocular symptoms. These tend to be small lesions with few associated neurologic symptoms or signs.

Fascicular midbrain portion

Lesions in the fascicular midbrain portion can lead to complete or incomplete palsies that may be indistinguishable from lesions outside the midbrain. Because of the proximity of the fascicular portion of the nerve to other structures in the midbrain, lesions typically produce neurologic symptoms associated with the damaged structures. Several syndromes have been recognized and are described below.

Nothnagel syndrome, which results from a lesion involving the fascicles and the superior cerebellar peduncle, includes third cranial nerve palsy and ipsilateral cerebellar ataxia.

Claude syndrome, although caused by involvement of the same structures as Nothnagel syndrome, includes third cranial nerve palsy and contralateral cerebellar ataxia. [2]

Benedikt syndrome results from involvement of the fascicles and the red nucleus and includes third cranial nerve palsy, ipsilateral flapping hand tremor (rubral tremor), and ataxia.

Weber syndrome results from a slightly more ventral lesion at the level of the fascicles in the midbrain with involvement of the cerebral peduncle, giving rise to third cranial nerve palsy along with contralateral hemiplegia or hemiparesis.

Subarachnoid portion

The fascicles of the third cranial nerve exit the mid brain through the medial aspect of the cerebral peduncles and are not near any of the other cranial nerves at this point.

The findings of third cranial nerve palsy tend to occur in isolation from lesions in this location. The pupil fibers are superficially located within the third cranial nerve in this location; therefore, pupil involvement is a common presentation of subarachnoid space compression of the nerve (eg, aneurysm).

Since the most common lesion to affect the third cranial nerve in the subarachnoid space is aneurysm, the signs and symptoms of subarachnoid hemorrhage, including sudden severe headache, stiff neck, and loss of consciousness, may be present.

Infundibulum refers to widening of the proximal segment of the posterior communicating and other arteries, and, unlike aneurysm in this location, it is usually asymptomatic. A case of posterior communicating artery infundibulum has been reported to cause recurrent ipsilateral third cranial nerve palsy and headache that masqueraded as ophthalmoplegic migraine. [3]

Ophthalmoplegic migraine presents in childhood with recurring bouts of unilateral headache and ipsilateral third cranial nerve palsy that can last several weeks at a time. The link to migraine in general has come under question because many or most of these patients demonstrate thickening and enhancement of the cisternal portion of the third cranial nerve on MRI with gadolinium. [4]

Basal meningeal infection, neoplastic infiltration, and miscellaneous inflammatory lesions may involve the third and all the other cranial nerves. The primary symptoms of meningitis are often present, including headache, stiff neck, fever, and alteration of consciousness. Eventually, these diseases tend to involve other cranial nerves, which is not the case with a very localized lesion, such as berry aneurysm.

Cavernous sinus portion

The third cranial nerve is more susceptible to compression against the interclinoid ligaments above and the petroclinoid ligament below than are the other cranial nerves in the cavernous sinus. For this reason, isolated third cranial nerve palsy may result from lateral extension of pituitary adenoma or other primary intrasellar mass.

More diffuse lesions within the cavernous sinus, often inflammatory in nature, typically give rise to simultaneous involvement of the third, fourth, sixth, and first 2 divisions of the fifth cranial nerves in various combinations, which serve to define a cavernous sinus syndrome. The sixth cranial nerve is the most commonly affected in these cases, as it resides within, and not around, the cavernous sinus. Nonspecific, idiopathic, and presumed granulomatous inflammation within the cavernous sinus is referred to as Tolosa-Hunt syndrome, which produces an acute, steroid-responsive, painful ophthalmoplegia.

Involvement of the fourth cranial nerve in the setting of a third cranial nerve palsy should be assessed by evaluating for intorsion in downgaze. The absence of intorsion suggests concomitant fourth (on top of third) cranial nerve palsy and may localize to the ipsilateral cavernous sinus.

Often, the involvement of the first 2 divisions of the fifth cranial nerve (trigeminal) presents with severe pain and numbness in the face, including the forehead back to the interaural line and the cheek down to the angle of the mouth. The pain may be constant and burning with unpleasant paresthesia, or it may include a lancinating component that can be confused with trigeminal neuralgia.

Carotid artery dural branch to cavernous sinus fistulas typically present with third cranial nerve palsy plus other cranial nerve involvement in the cavernous sinus and proptosis with arterialized episcleral/conjunctival veins due to a large volume shunt of arterial blood into the anterior draining veins of the cavernous sinus. Isolated third cranial nerve involvement without the orbital congestion can occur when the primary drainage is posterior from the cavernous sinus, the so-called white eye fistulas. [5]

Orbital portion

Lesions (eg, inflammatory, infectious, infiltrative, neoplastic, vascular, among others) in the orbit tend to produce associated proptosis, lid swelling, conjunctival injection, and chemosis.

There also may be involvement of the other cranial nerves that innervate extraocular muscles (fourth and sixth) or involvement of the muscles themselves.

Nonspecific idiopathic inflammation in the orbit is referred to as idiopathic orbital inflammatory syndrome (ie, orbital pseudotumor). Granulomatous and nongranulomatous lesions may also produce orbital involvement of the third cranial nerve.



Initially, physical findings attributable to involvement of the third cranial nerve are described (eg, ptosis, mydriasis, ophthalmoplegia). Subsequently, additional physical findings that are associated with lesions of particular portions or segments of the third cranial nerve are described.

Unilateral third cranial nerve palsy

Horizontal deviation is divergent or temporal (exotropia) because of weakness of the medial rectus muscle of the involved side. Vertical deviation results from weakness of the superior rectus, inferior oblique (both elevators), and inferior rectus (depressor) muscles.

Residual function of both the superior oblique muscle (depressor, intact fourth cranial nerve function) and the lateral rectus muscle (abductor, intact sixth cranial nerve function) tends to produce downward and outward deviation of the involved eye. A way to remember this combination is to think of a losing boxer, "down and out."

In very mild cases, one might have to resort to eliciting latent deviation or phoria with Maddox rod or alternate cover testing (to dissociate the 2 eyes and interrupt fusion).

Ptosis results from weakness of the levator palpebrae, and this often is complete or nearly so, in which case the pupil is covered and the patient cannot see from the involved eye.

Milder degrees of ptosis are examined best using measurements of the palpebral fissure width; more information can be gained from measuring the levator function and margin reflex distances (MRD), as follows:

  • The examiner sits in front of the patient and directs a point source of light (eg, handlight, Finnoff head, penlight) into both the eyes of the patient.

  • The examiner can observe the pinpoint light reflex in the center of the cornea. The position of this reflex is not affected by deviation of the eye, which makes it a useful reference point for measuring the distance to the upper and lower lids, respectively.

  • The MRD1 usually refers to the distance from the light reflex to the upper lid margin, and the MRD2 is the distance to the lower lid margin.

  • Levator palpebrae weakness reduces the MRD1 but will not affect the MRD2. On the other hand, ptosis from ocular sympathetic palsy (Horner or Claude Bernard syndrome) causes weakness of Mueller muscle in both the upper and lower lids, with consequent reduction of both the MRD1 and the MRD2.

  • Pseudoptosis from widening of the contralateral palpebral fissure may result from mild or old contralateral seventh cranial nerve lesion and orbicularis oculi weakness. In both these cases, MRD1 and MRD2 are increased on the side opposite to the apparent ptosis.

  • Careful examination of facial muscle strength and symmetry usually confirms the cause of the apparent ptosis in these cases.

Pupillary dilatation and sluggish or absent reaction to light results from involvement of parasympathetic fibers that originate in the Edinger-Westphal subnucleus of the third cranial nerve complex, as follows:

  • Fascicular or peripheral nerve involvement caused by compressive lesions often affects these autonomic fibers because they are situated very superficially within the nerve trunk.

  • This contingent of fibers are medially placed as the nerve exits the brainstem and gradually migrate to a more inferior and lateral position as they proceed anteriorly along the nerve.

If there is partial preservation of parasympathetic pupillary innervation with third cranial nerve disorders, the pupil on the involved side may react to light nearly as briskly as the pupil of the other eye, as follows:

  • Distinguishing pupillary involvement caused by third cranial nerve lesions from ocular sympathetic palsy (Horner or Claude Bernard syndrome) or physiological anisocoria requires detailed examination of pupil size in dim and in bright, ambient light. Third nerve palsy mydriasis can coexist with Horner syndrome–related miosis (eg, cavernous sinus lesion), and the two pupillary effects may obscure the diagnosis or cancel out the anisocoria in ambient lighting.
  • With sphincter weakness due to parasympathetic involvement in third cranial nerve lesions, the involved pupil is larger than the fellow pupil. However, with concomitant Horner syndrome or aberrant regeneration of the pupil, the pupil may be smaller rather than larger in a third nerve palsy.
  • The size difference between the 2 pupils (anisocoria) is greater in bright light (when the sphincter is called upon to act most strongly) and lesser in dim light (when the sympathetically innervated dilator fibers are the dominant contributors to pupil size). The reverse is true for ocular sympathetic lesions, in which the pathological pupil is the smaller one and the difference (anisocoria) is greater in dim light than in bright light. The anisocoria remains the same in dim and bright light in simple central anisocoria, also called physiological anisocoria.

Nuclear portion

Nuclear third cranial nerve palsy demonstrates, in addition to the ipsilateral findings, contralateral ptosis or no ptosis (single central caudate subnucleus innervates both lids) and elevation palsy (superior rectus subnucleus is crossed).

The contralateral ptosis stems from the bilateral distribution of innervation to the levator from the caudal central subnucleus.

Ptosis is typically more complete ipsilateral to the lesion because function is lost in both the ipsilateral neural cell bodies and their fibers on the lesioned side, plus the crossed fibers coursing through the lesion from the other side.

There is partial ptosis contralateral to the lesion because of the residual integrity of the uncrossed neural cell bodies and fibers from the caudal central subnucleus contralateral to the lesion.

Superior rectus nucleus output is totally contralateral with fascicles from the nucleus on one side coursing through the opposite superior rectus subnucleus. A lesion of the superior rectus subnucleus on one side causes bilateral elevation palsy. The deficit ipsilateral to the lesioned nucleus reflects involvement of fascicles coming from cell bodies on the opposite side, and the deficit contralateral to the lesion reflects loss of the cell bodies in the lesioned nucleus.

Fascicular midbrain portion

Ask the patient to hold both arms outstretched in front of them.

Patients with Benedikt syndrome have a gross "flapping" tremor that has been attributed to red nucleus involvement, usually from midbrain infarction. The tremor and ataxia are ipsilateral to the lesion and to the third cranial nerve palsy.

In Weber syndrome, the patient usually has a dense hemiplegia contralateral to the third cranial nerve palsy resulting from a lesion that also involves the pyramidal tract motor pathways in the cerebral peduncle. This should be obvious on simple inspection of the patient, since it is usually a fairly prominent hemiplegia.

Subtle hemiparesis may be observed by asking the patient to hold both arms outstretched forward with palms rotated upward. Slight pronation of the turned-up hand and downward drift of the outstretched arm are sensitive indicators of even very mild hemiparesis.

The hemiparetic gait is also characteristic with foot drop causing circumduction as the involved leg is swung out and forward before the next step. The arm on the involved side typically is held semiflexed at the elbow and wrist as the patient walks.

Another subtle sign in very mild hemiparesis is loss of the associated arm swing on the involved side as the patient walks.

Fascicular subarachnoid portion

Many patients who have had subarachnoid hemorrhage from rupture of a berry aneurysm have alteration of consciousness and may be difficult to examine. Even if they cannot co-operate with ocular motility assessment, the findings of a dense third cranial nerve palsy should be obvious. The eye on the involved side is deviated "down and out" from residual tone in the fourth cranial nerve (superior oblique muscle) and the sixth cranial nerve (lateral rectus muscle). [6, 7]

Usually, there is prominent ptosis also, but this may be difficult to observe if the patient is unconscious with eyes closed. Efforts should be made to arouse the patient at least to the point that there is some effort at eye opening, when the ptosis should be apparent.

The dilated, light-fixed pupil should be apparent on inspection without requiring any co-operation from the patient.

Pupillary involvement is the rule in third cranial nerve palsy resulting from posterior communicating artery aneurysm, with or without overt subarachnoid hemorrhage. In more than 95% of aneurysmal palsies, the pupil reacts sluggishly to light or is fixed and dilated, but, in 73%, of ischemic palsies, the pupil is spared. These observations have led to the pupil-sparing rule, which states that patients with third nerve palsies that spare the pupil do not have aneurysms and can be safely managed expectantly. Three important caveats are as follows: [8, 9, 10, 11, 12, 13, 14, 15]

  • Patients must have complete paralysis of the ocular muscles of the cranial nerve III and complete sparing of the pupil.
  • This rule should be applied sparingly to patients aged 20-50 years, an age group in whom ischemic infarcts are uncommon.
  • Patients should have isolated third nerve palsies.

This is probably because the pathophysiology of the third cranial nerve lesion involves leakage of blood from the aneurysm dome into the nerve across its outer margin. The pupil fibers are located very superficially and are nearly always involved in this process. On the other hand, pupil-sparing third cranial nerve palsy is a hallmark of ischemic lesions that tend to involve the central core of the nerve. This is the type of nonsurgical or medical third cranial nerve palsy that often results from microvascular disease and tends to resolve uneventfully within a few weeks.

Fascicular cavernous sinus portion

Fourth cranial nerve palsy

Fourth cranial nerve palsy is difficult to diagnose in the presence of third cranial nerve palsy because the small increment of depressor deficit (superior oblique muscle) cannot be discerned readily from the depressor palsy that results from weakness of the third nerve innervated depressor (inferior rectus muscle).

The superior oblique muscle depresses the globe most efficiently with the eye in adduction, a position that may not be achievable with medial rectus palsy from third cranial nerve involvement.

The best marker for fourth cranial nerve function in the presence of dense third cranial nerve palsy is intorsion of the globe on attempted down gaze. If no intorsion is present, one should suspect concomitant fourth cranial nerve palsy as part of a cavernous sinus syndrome. Torsion of the globe can be discerned by simultaneously watching landmarks, such as conjunctival vessels lateral and medial to the iris. With intorsion, the lateral vessels rise and the nasal vessels drop.

Trigeminal nerve sensory function

Trigeminal nerve sensory function can be tested with the aid of a cotton-tipped applicator. Tease a few fibers of the cotton into a pointed bundle by twirling it between the thumb and the forefinger after a small tuft of cotton is pulled free of the tip.

This wisp of cotton can be touched to the cornea near the limbus to test the corneal reflex. It should elicit a blink response that is symmetric between the sides.

Failure to blink may indicate reduced sensory function in the first division of the trigeminal nerve on the side of decreased response. The cotton wisp can be dragged lightly across the skin in various locations. With the eyes closed, the patient is asked to indicate when it is felt.

Asymmetry of light touch between sides should be sought. The wooden stick, when broken, can serve as a "pinprick" tester. Usually, the break is jagged and there is a pointed end that can be used like a pin to test for pain sensation. Lightly tap the point on the skin at various points. The patient should compare the "sharpness" of the feeling at homologous points on the right and left sides of the face.

Orbital portion

Orbital signs are usually matters for direct inspection, including conjunctival injection and chemosis, proptosis, and lid swelling.

Obtain exophthalmometry measurements with a Hertel instrument or similar equipment since it provides a more sensitive measure of relative proptosis.



Any focally destructive lesion along the course of the third cranial nerve can cause oculomotor nerve palsy or dysfunction. A painful pupil-involved oculomotor nerve palsy may result from a life-threatening intracranial aneurysm. See the table below.

Table 1. Etiology of Isolated Third Nerve Palsy [16, 17, 18, 19, 20, 21] (Open Table in a new window)


Percentage of overall cases (%)

Head trauma












Some of the most frequent causes include the following:

  • Nuclear portion

    • Infarction

    • Hemorrhage

    • Neoplasm

    • Abscess

  • Fascicular midbrain portion

    • Infarction

    • Hemorrhage

    • Neoplasm

    • Abscess

  • Subarachnoid portion

    • Aneurysm

    • Infectious meningitis - Bacterial, fungal/parasitic, viral

    • Meningeal infiltrative

    • Carcinomatous/lymphomatous/leukemic infiltration, granulomatous inflammation (sarcoidosis, lymphomatoid granulomatosis, Wegener granulomatosis) [22]

    • Ophthalmoplegic migraine

  • Cavernous sinus portion

    • Tumor - Pituitary adenoma, meningioma, craniopharyngioma, metastatic carcinoma

    • Pituitary apoplexy (infarction within existing pituitary adenoma) [23]

    • Vascular

    • Giant intracavernous aneurysm

    • Carotid artery-cavernous sinus fistula

    • Carotid dural branch-cavernous sinus fistula

    • Cavernous sinus thrombosis

    • Ischemia from microvascular disease in vasa nervosa

    • Inflammatory - Tolosa-Hunt syndrome (idiopathic or granulomatous inflammation)

  • Orbital portion

    • Inflammatory - Idiopathic orbital inflammatory syndrome (orbital pseudotumor, orbital myositis)

    • Endocrine (thyroid orbitopathy mimicking third nerve palsy)

    • Tumor (eg, hemangioma, lymphangioma, meningioma)