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Cranial Nerve 3 Palsies

Home / Neuro-Ophthalmology / Efferent Disorders

Authors: Amanda Redfern, MD; Meagan Seay, DO

Date: 07/10/21

Keywords/Main Subjects: Cranial nerve, Oculomotor nerve


Cranial nerve 3 (CN3) is aptly named the oculomotor nerve as it innervates the majority of the extraocular muscles. Specifically, it innervates the superior rectus (SR), medial rectus (MR), inferior rectus (IR), and inferior oblique (IO) muscles. In addition, CN3 innervates the levator palpebrae superioris (LPS) which is the major muscle of lid elevation, the ciliary muscle which is responsible for accommodation, and the pupillary sphincter muscle which is responsible for pupillary constriction.

The CN3 nucleus is located in the rostral midbrain. Each sub-function of CN3 has its own subnucleus – i.e. SR subnucleus, MR subnucleus, IR subnucleus, IO subnucleus, Edinger-Wesphal subnucleus, and LPS subnucleus. Of note, the right and left CN3 nuclei share one LPS subnucleus, but otherwise have separate subnuclei. All extraocular muscle subnuclei are ipsilateral to the muscle they innervate except for the SR nuclei, which innervate the contralateral SR muscle.

CN3 palsies are typically categorized as partial vs. complete and pupil-sparing vs. pupil-involving. A complete CN3 palsy refers to complete dysfunction of the LPS, SR, MR, IR, and IO. These patients will present with complete ptosis. Diplopia is present when the ptotic lid is elevated, revealing an eye that is both exotropic and hypotropic. The eye is unable to adduct or supraduct. There may still by subtle infraduction if CN4 remains intact, although the more prominent indicator of normal CN4 function would be intorsion of the eye in attempted down gaze. Partial CN3 palsies may present with varying degrees of ptosis and ophthalmoplegia. Inferior or superior division of the palsy can be seen in lesions peripheral to the bifurcation of the nerve (anterior cavernous sinus).

Pupil-sparing and pupil-involving is an important distinction to make as it can have implications of the likely etiology of the CN3 palsy. The pupillary fibers of CN3 run peripherally within the nerve while the motor fibers run centrally within the nerve. Thus, a compressive lesion will generally cause a pupil-involving CN3 palsy as it will contact and compress the peripheral pupillary fibers first. This distinction is more salient in cases of complete CN3 palsies, in which a lack of pupillary involvement would suggest a non-compressive etiology because the amount of mass effect needed to cause complete ophthalmoplegia would most likely cause pupillary dysfunction. Exceptions are exceedingly rare, but do exist, which is why most providers would recommend urgent neuro-imaging to rule out an aneurysm regardless of pupil involvement1.

In addition to noting the completeness and pupil involvement of a CN3 palsy, the examiner should also look for signs of aberrant regeneration. These signs include lid elevation with adduction or infraduction, constriction of the pupil with adduction, and retraction of the globe with attempted vertical ductions. Aberrant regeneration of CN3 suggests a compressive or traumatic etiology.




The most common etiology of a CN3 palsy is microvascular (aka ischemic). Patients typically present with orbital pain or headache preceding the onset of diplopia or concurrent with the onset of diplopia2. Risk factors include hypertension, diabetes, advanced age, atherosclerosis, smoking, and hypercholesterolemia3. These cranial nerve palsies tend to be pupil-sparing. It is thought that the pupillary fibers are less vulnerable to ischemic insult given their peripheral location. Studies suggest that as many as 38% will have up to 2 mm of anisocoria, though it would be rare to have a dilated unreactive pupil4.

Diagnosis of a microvascular CN3 palsy is based on clinical history and exam. Neuro-imaging should be obtained to rule out an aneurysm (see below), which can be acutely life-threatening. Likewise, giant cell arteritis should be considered and an ESR and CRP should be obtained in the appropriate clinical context. Attention should be paid to the patient’s systemic risk factors for developing a microvascular CN3 palsy, with review of vitals and pertinent labs. Patients should work closely with their primary care providers to manage any risk factors.

The majority of microvascular CN3 palsies will resolve spontaneously over the course of 3 months. Depending on the degree of ptosis, patients may not be symptomatic with diplopia initially. If and/or when they become symptomatic with diplopia, they can occlude or patch the paretic eye as a temporary treatment measure. In most cases, the degree of strabismus on initial presentation is too large for Fresnel prism placement. Although most patients will have a full recovery, some will have residual strabismus that can be treated with prismatic correction and/or surgery. However, patients should be advised against strabismus surgery unless they have residual strabismus with stable measurements for a minimum of 6 months, preferably a year.



Compression of the third nerve anywhere along its course can cause a third nerve palsy. Because the pupillary fibers run along the peripheral aspect of the nerve, pupil-involvement is expected. Patients may or may not present with headache or pain depending on the etiology. On exam, you may see evidence of aberrant regeneration of the third nerve, which can manifest as: greater pupillary constriction with adduction/convergence than with light reaction, lid retraction with adduction or infraduction (“Pseudo Von-Graefe Sign”), adduction of the eye on attempted upward or downward gaze, and/or limitation of elevation and depression of the eye with retraction of the globe on attempted vertical movement.

The most acutely life-threatening etiology of a third nerve palsy in a patient that is alert and oriented is an aneurysm. The classic scenario is of a patient presenting with a complete pupil-involving third nerve palsy due to a posterior communicating artery aneurysm. Basilar artery and internal carotid artery aneurysms can also cause third nerve palsies. Because aneurysms are life-threatening, it is important to promptly obtain neurovascular imaging (i.e. CTA or MRA of the head). Though rare, an aneurysm can cause a pupil-sparing third nerve palsy depending on its location with respect to the pupillary fibers. Therefore, lack of pupil involvement should not preclude neurovascular imaging.

Uncal herniation is another acutely life-threatening cause of a third nerve palsy. The classic presentation is acute loss of consciousness, ipsilateral mydriasis, and contralateral hemiparesis. However, early signs may also include headache, altered mental status, nausea, and vomiting. Similarly, pituitary apoplexy can cause acute compressive third nerve palsy that may also be associated with headache and altered mental status. Other cranial nerve palsies may be present depending on the size and location.

Tumors along the course of the third cranial nerve may present much more insidiously. The combination of ipsilateral third nerve palsy and ataxia is seen in Nothnagel syndrome, which is due to a tumor of located in the midbrain tectum, involving the quadrigeminal plate5. In cases that do not resolve over 3 months and have normal initial head imaging (including neurovascular imaging), an MRI brain with cranial nerve protocol should be considered.



Midbrain strokes can cause both nuclear and fascicular third nerve palsies. Depending on the size and location of the stroke, any combination of the subnuclei may be involved in a nuclear third nerve palsy. As such, a patient with a nuclear infarct can present with a partial third nerve palsy, complete third nerve palsy, pupil-sparing or pupil-involving third nerve palsy, bilateral ptosis, contralateral supraduction deficit, parinaud’s syndrome, etc. Strokes along the course of the third nerve fascicle as it travels from the nucleus to its root exit zone can cause ipsilateral third nerve palsies with additional neurological deficits. The classic fascicular third nerve palsy syndromes are:


Dorsal Midbrain Syndrome

Dorsal midbrain syndrome (aka Parinaud’s syndrome) is classically the triad of up gaze palsy, convergence retraction nystagmus, and light-near dissociation. While there are many different etiologies, the most common causes are pineal region tumor, midbrain hemorrhage, midbrain infarct, and midbrain tumor. The complete triad is seen in 65% of patients with dorsal midbrain syndrome6. Other signs on exam may include bilateral lid retraction (Collier’s sign), papilledema, ataxia, exotropia, and convergence insufficiency. The treatment and prognosis is based on the underlying etiology.

Other Causes

Pediatric Causes



  1. Trobe J. Third Nerve Palsy and the Pupil Footnotes to the Rule. Arch Ophthalmol. 1988;106(5):601-602.
  2. Wilker SC, Rucker JC, Newman NJ, Biousse V, Tomsak RL. Pain in ischaemic ocular motor cranial nerve palsies. Br J Ophthalmol. 2009 Dec;93(12):1657-9. doi: 10.1136/bjo.2008.155150. Epub 2009 Jun 30. PMID: 19570771; PMCID: PMC2998753.
  3. Jacobson DM, McCanna TD, Layde PM. Risk factors for ischemic ocular motor nerve palsies. Arch Ophthalmol. 1994 Jul;112(7):961-6. doi: 10.1001/archopht.1994.01090190109029. PMID: 8031277.
  4. Dhume KU, Paul KE. Incidence of pupillary involvement, course of anisocoria and ophthalmoplegia in diabetic oculomotor nerve palsy. Indian J Ophthalmol. 2013 Jan-Feb;61(1):13-7. doi: 10.4103/0301-4738.99999. PMID: 23275215; PMCID: PMC3554988.
  5. Ruchalski K, Hathout GM. A medley of midbrain maladies: a brief review of midbrain anatomy and syndromology for radiologists. Radiol Res Pract. 2012;2012:258524. doi: 10.1155/2012/258524. Epub 2012 May 22. PMID: 22693668; PMCID: PMC3366251.
  6. Shields M, Sinkar S, Chan W, Crompton J. Parinaud syndrome: a 25‐year (1991–2016) review of 40 consecutive adult cases. Acta ophthalmologica. 2017 Dec;95(8):e792-3.

Identifier: Moran_CORE_125860
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