The Oculomotor Nerve

This episode deals with the anatomy of the Oculomotor nerve and the clinical features of patients presenting with oculomotor palsy at various locations through its course in the brain.

Chapters

• 0:00 Introduction
• 1:02 Pre-test MCQs
• 3:00 The anatomy of Oculomotor nerve
• 7:05 Clinical features of third nerve palsy
• 7:44 Localisation of oculomotor nerve palsy
• 8:02 Lesions of the Oculomotor nerve nucleus
• 11:15 Lesions of the Oculomotor nerve fasciculus
• 15:02 Lesions of the Oculomotor nerve in the subarachnoid space
• 16:09 Lesions in the Cavernous sinus
• 17:22 Lesions in the Superior orbital fissure
• 18:02 Intra-orbital lesions
• 18:43 Congenital third nerve palsy
• 19:22 Post-test MCQs
• 22:36 Outro

Transcript

Welcome to the 'Clinical Neurology with KD' podcast season 2. After the overwhelming response to Season 1, which focused on neurological localization for medical students, we're back with a brand-new season dedicated to an exciting and often challenging topic of Neuro-ophthalmology. If you haven't listened to Season 1, I highly recommend doing so. It will help you understand the fundamentals of neurological localization, which form the foundation for this season. The podcast aims to help medical students enjoy the process of learning neurology by teaching it from a clinical perspective. This season will benefit medical students, medicine, ophthalmology, neurology residents, and consultants. Each episode starts with a pretest of multiple-choice questions based on the topic discussed. The answers will be provided at the end of the episode. Study materials, illustrations, and clinical resources for the podcast are available in the show description and on the neurologyteachingclub.com website and Instagram page. I am your host, Dr Krishnadas N C, and let's get started.

We will start this season of neuro-ophthalmology with the Oculomotor nerve. We will begin with pre-test multiple-choice questions based on the content of our episode. We will discuss the answers at the end of the session. 

1. Which of the following statements about the oculomotor nerve nucleus complex is TRUE?

A) It lies in the pons at the level of the inferior colliculus

B) The superior rectus subnucleus supplies the ipsilateral eye

C) The medial rectus subnucleus is isolated and easily affected by lesions

D) The Edinger-Westphal nucleus provides parasympathetic fibers to the pupil and ciliary muscle

2. A lesion affecting the unilateral superior rectus subnucleus will cause which of the following findings?

A) Ipsilateral superior rectus palsy only

B) Contralateral superior rectus palsy only

C) Bilateral superior rectus palsy

D) No effect on the superior rectus

3. Which of the following is TRUE regarding fascicular third nerve palsy?

A) It always presents with contralateral third nerve involvement

B) It resembles a peripheral third nerve palsy but can be associated with brainstem signs

C) It never involves the pupil

D) It is commonly caused by diabetic neuropathy

4. Which of the following is a key feature of cavernous sinus lesions affecting the oculomotor nerve?

A) Isolated third nerve palsy with pupillary sparing

B) Presence of Horner's syndrome due to sympathetic fiber involvement

C) No involvement of other cranial nerves

D) No associated pain

5. Which condition is most likely to cause pupillary sparing in third nerve palsy?

A) Posterior communicating artery aneurysm

B) Cavernous sinus lesion

C) Ischemic third nerve palsy (diabetes)

D) Brainstem infarction involving the oculomotor nucleus

The oculomotor nerve conveys motor fibers to extraocular muscles and parasympathetic fibers to the pupil and ciliary body. The oculomotor nerve nucleus complex lies in the midbrain at the level of the superior colliculus. It lies ventral to the aqueduct of Silvius in the peri-aqueductal grey and dorsal and medial to the medial longitudinal fasciculus. The oculomotor complex consists of one unpaired and four paired rostrocaudal complexes. The right and the left nuclei share the unpaired column. It forms a pair of Edinger Westphal nucleus rostrally and Levator Palpebra Superioris subnucleus caudally. The Edinger-Westphal (EW) nuclei are part of the craniosacral, parasympathetic division of the autonomic nervous system. The EW subnucleus is a single structure that provides parasympathetic innervation to both sides. It is spread throughout the length of the oculomotor complex with a paired rostral portion and an unpaired medial and caudal portion. Preganglionic fibers from the Edinger-Westphal (EW) nuclei travel to the ciliary ganglion. Postganglionic fibers supply the pupillary sphincter and ciliary muscle for accommodation. 

Among the four paired subnuclei, the most medial is the Superior rectus subnuclei. It is the only oculomotor subnuclei that supply the opposite eye. Decusating fibers go through the opposite superior rectus sub-nuclei. As a result, damage to unilateral superior rectus subnuclei can cause bilateral superior rectus denervation. A significant clue to a nuclear third nerve palsy is superior rectus weakness in the opposite eye. The lateral three paired subnuclei are dorsal, intermediate, and ventral, supplying the inferior rectus, inferior oblique, and medial rectus, respectively. The neurons innervating the medial rectus muscle are located in three distinct areas of the oculomotor nuclear complex. Therefore, isolated medial rectus palsy caused by the involvement of the medial rectus subnucleus is unlikely. Isolated palsies of individual third nerve innervated muscles can occur due to brainstem lesions that affect their specific subnuclei. However, these are typically indicative of isolated muscle disease or intra-orbital lesions.

The part of the third cranial nerve inside the midbrain after leaving the oculomotor nuclear complex is called the fasciculus. The nerve fibers cross the Medial Longitudinal Fascicle and the decussating fibers of the superior cerebellar peduncle. The fibers pass through the red nucleus before coming out of the anterior surface of the brainstem medial to the cerebral peduncle in the interpeduncular fossa above the pons. The fibers innervating LPS and SR lie laterally in the fasciculus.

Upon exiting the brainstem, the oculomotor nerve traverses the subarachnoid space and passes between the superior cerebellar and the posterior cerebral artery. It runs anteriorly parallel to the posterior communicating artery. It then courses forward near the medial part of the uncus of the temporal lobe. It lies on the free edge of the tentorium cerebelli. Here, it is at risk of compression due to uncal herniation. The parasympathetic fibers lie superficially on the dorsomedial surface throughout the nerve's subarachnoid course. 

The nerve pierces the dura just lateral to the posterior clinoid process and enters the lateral wall of the cavernous sinus. There, it lies over the trochlear nerve medial to the ophthalmic division of the trigeminal nerve and superior to the sixth cranial nerve. Upon reaching the superior orbital fissure, the oculomotor nerve divides into superior and inferior divisions. The nerves enter the orbit through the superior orbital fissure and pass through the Annulus of Zinn. The superior division supplies the SR and LPS, while the inferior division supplies other IR, IF, MR, and the presynaptic parasympathetic outflow to the ciliary ganglion. 

A third nerve palsy results in ipsilateral paralysis of

1. Adduction due to medial rectus weakness
2. Elevation due to superior rectus and inferior oblique
3. Depression due to the inferior rectus
4. There will be ptosis due to levator palpebrae weakness.
5. The involvement of parasympathetic fibers from the Edinger-Westphal nucleus to the ciliary ganglion causes pupillary dilation and accommodation paralysis. 

The patient presents with Binocular diplopia and ptosis with the eye down and out. Diplopia is absent if ptosis is complete. Less frequently, they can present as awareness of an enlarged pupil or blurred monocular vision at near.

Localization of the lesion

When a patient develops a third nerve palsy, the localization can be in the oculomotor nerve nuclear complex or fasciculus in the brainstem, the subarachnoid space, the cavernous sinus, the superior orbital fissure, or inside the orbital cavity. 

Nuclear lesion

The prototype presentation of a nuclear third nerve palsy is ipsilateral complete third nerve palsy with opposite eye ptosis and superior rectus palsy. The eye is down and out with bilateral ptosis and superior rectus palsy. The pupil is variably involved because each Edinger-Westphal nucleus supplies both pupils. If both Edinger-Westphal nuclei are involved, the pupil will definitely be involved. It can be involved in unilateral EW nuclei lesions as well. Isolated levator subnucleus palsy can cause isolated bilateral ptosis. Other isolated subnucleus palsy can cause the corresponding isolated muscle palsy. For example, IR subnucleus involvement can cause isolated IR palsy. The exemption to this is the MR subnucleus. The subnucleus is part of a complex arrangement involving the dorsolateral and ventral parts of the oculomotor complex. So, isolated involvement without involving other subnuclei is rare. 

Other rare nuclear involvement

These are mentioned to inform you of the rare presentations of nuclear third nerve involvement. One need not remember all these presentations but should be aware that patients can present in varied ways.

1. Contralateral SR is weak with spared ipsilateral SR due to a lesion in the contralateral midbrain involving crossing-over fibers.
2. Bilateral third nerve palsy with sparing of LPS if nuclear lesion which spares the central caudal LPS subnucleus.
3. Isolated bilateral ptosis occurs due to the lesion of the central caudal levator palpebrae superioris subnucleus without the involvement of the rest of the oculomotor nucleus.
4. Lesions can affect the LPS subnucleus and bilateral SR subnucleus alone, sparing the rest of the oculomotor nucleus and causing bilateral ptosis with SR palsy.
5. The supranuclear gaze pathway lies close to the oculomotor nuclear complex, the involvement of which can cause contralateral horizontal gaze palsy along with ipsilateral nuclear third nerve palsy.
6. Isolated IR palsy can occur due to a lesion of the IR subnucleus. It can also occur due to the involvement of the supranuclear descending tracts from riMLF to IR subnucleus.
7. Nuclear lesions affecting the pupil indicate a rostral, dorsal insult and are often associated with nuclear or supranuclear vertical gaze palsy.
8. Bilateral oculomotor nuclear complex involvement will result in bilateral third nerve palsy with bilateral fixed dilated pupils. Often, the patient will experience total ophthalmoplegia due to the involvement of the bilateral riMLF, interstitial nucleus of Cajal, bilateral horizontal saccades, and smooth pursuit pathways.
9. Fascicular involvement can often accompany nuclear lesions, altering the clinical picture, as the same paramedian penetrating branches of the basilar artery supply both.

Fascicular lesion

A fascicular lesion resembles a peripheral oculomotor nerve palsy. All the muscles supplied by the oculomotor nerve and the pupil are involved when the fascicle is completely damaged. The opposite eye is normal. The involvement of other brainstem structures helps in localizing the lesion. Along with the third nerve, the red nucleus, superior cerebellar peduncle, and pyramidal tract can be involved, helping localize the lesion to the brainstem rather than in the subarachnoid space or cavernous sinus. These additional findings can help in lateralizing and assessing the extent of the lesion in the brainstem. The various midbrain syndromes are discussed in detail in season 1, episode 9, on localization of lesions involving the brainstem. 

1. Unilateral paramedian thalamopeduncular infarction can cause ipsilateral third nerve palsy and contralateral downbeat nystagmus.
2. Benedikt syndrome- A ventral midbrain lesion involving the red nucleus and third nerve fascicle will result in ipsilateral third nerve palsy with contralateral tremor called the Benedikt syndrome.
3. Nothnagel syndrome- A lesion involving the third nerve fascicle and superior cerebellar peduncle will result in an ipsilateral third nerve with contralateral ataxia called the Nothnagel syndrome. The lesion site is more dorsal than in Benedikt syndrome.
4. Claude syndrome- A more extensive mesencephalic tegmental lesion involving both the red nucleus and superior cerebellar peduncle along with the third nerve fascicle will result in a combination of Benedikt, and Nothnagel called the Claude syndrome. The patient will have ipsilateral third nerve palsy with contralateral tremor and ataxia. Please see the schematic diagram on the website to understand these syndromes better.
5. Midbrain lesions can cause displacement of the pupils and irregularities of the pupil, which is called midbrain corectopia.
6. Unilateral and rarely bilateral brainstem fascicular involvement can occur without other long tract signs or symptoms.
7. Fascicular or nuclear third nerve palsies can sometimes be associated with ipsilateral ptosis and contralateral eyelid retraction, a combination known as the plus-minus lid syndrome. The syndrome occurs due to a small lesion in the paramedian mesencephalon that affects the ipsilateral levator palpebra (LP) fascicles as they emerge from the central caudal nucleus (CCN) while the CCN remains intact. Additionally, the lesion impacts the inhibitory pathways, specifically the mesencephalic M-group neurons, which project onto the opposite Levator Palpebra motor neurons just before they enter the CCN.
8. Fascicular lesions can spare pupils.

Fascicular lesions may cause third nerve palsies limited to specific oculomotor-innervated muscles due to the intra-axial topographic arrangement of fibers. The third nerve fascicles in the ventral brainstem are arranged topographically from lateral to medial as follows: inferior oblique, superior rectus, medial rectus and LP, inferior rectus, and pupillary fibers. A rostral-caudal topographic arrangement has been suggested, with pupillary fibers located most superiorly, followed by fibers to the inferior rectus, inferior oblique, medial rectus, superior rectus, and levator palpebra superioris, in that order. This arrangement can explain the superior division oculomotor palsy pattern, i.e., superior rectus and LPS palsy, that can sometimes occur with midbrain lesions causing partial fascicular damage. Individual muscles can also be affected similarly.

Nuclear and fascicular lesions may be due to infarction, hemorrhage, tumor, infection, inflammation, or trauma. An imaging, ideally an MRI of the brain, will confirm the lesion.

Subarachnoid space lesion

A lesion in the subarachnoid space usually causes an isolated third CN palsy. The most common cause is a posterior communicating artery aneurysm. An ischemic third nerve palsy due to diabetes mellitus is a close differential for isolated third nerve palsy. In ischemic third nerve palsy, the pupil is not involved because the fibers are located peripherally, while ischemia affects the nerve's core. In compressive third nerve palsy, the pupil is affected early. A complete third nerve palsy affecting all the muscles with sparing of the pupil almost always rules out an aneurysmal compression. An aneurysm compressing the inferior portion of the third nerve can spare the dorsally situated pupillary fibers. A complete third nerve palsy affecting all the muscles with sparing of the pupil almost always rules out an aneurysmal compression. Similarly, up to 30% of diabetic third cranial nerve palsy can affect the pupil. The anisocoria in these cases is usually less than 1mm. Subarachnoid lesions can also cause isolated superior or inferior division oculomotor nerve palsy. Other than compression and ischemia, any infective or inflammatory lesion involving the subarachnoid space can cause third nerve palsy.

Cavernous sinus lesion

Other ocular motor nerves, such as the fourth and sixth cranial nerves and the ophthalmic division of the trigeminal, accompany the third cranial nerve in the cavernous sinus lesion. Any lesion here can affect the oculomotor nerve with or without the other cranial nerves. Combined ocular motor nerve palsies with sympathetic denervation causing ipsilateral Horner's syndrome are pathognomonic of a cavernous sinus lesion. Sensory fibers from the ophthalmic division of the trigeminal nerve join the oculomotor nerve on the lateral wall of the cavernous sinus. Lesions that develop from the lateral wall of the cavernous sinus will cause pain from the outset. In contrast, lesions originating from the medial wall typically initially result in painless ophthalmoplegia. Understanding this difference can provide insights into the etiology and localization of the cavernous sinus lesion based on the patient's history. Compressive cavernous sinus lesions can spare the pupil, as they preferentially involve the superior division of the oculomotor nerve. Lesions near the posterior clinoid process, as in breast carcinoma metastasis, may, for some time, affect only the third nerve as it pierces the dura. So cavernous sinus lesions can also occasionally present as isolated third nerve palsy.

Superior orbital fissure

The lesions of the oculomotor nerve in the superior orbital fissure produce clinical features similar to those of the cavernous sinus, with or without three, four, six, and ophthalmic division of trigeminal involvement. The only difference is the lack of sympathetic denervation. In other words, if there is sympathetic denervation, the lesion is in the cavernous sinus; if it is not there, it is not possible to differentiate between a cavernous sinus and a superior orbital lesion. The patient can have proptosis if the superior orbital lesion extends into the orbit. The etiologies of the cavernous and the superior orbital fissure are the same and include infective, inflammatory, and neoplastic causes.

Intra orbital lesion

Proptosis and optic nerve involvement are the pathognomic features of an intra-ocular third CN palsy. Swelling of the lid and chemosis can also occur. It is important to remember that flaccid muscles, due to denervation, can produce a proptosis of up to 3mm on the paretic side. Anything more than that is significant and always points to an intra-ocular pathology. Isolated involvement of the muscles innervated by either the superior or the inferior oculomotor branch has classically localized to the orbital lesion. However, we have already seen that the oculomotor nerve lesions, anywhere from fasciculus downwards, can show a divisional pattern.

Congenital third nerve palsy

Congenital third nerve palsy is rare and usually unilateral. It can occur isolated or with other defects like congenital facial palsy, cerebellar hypoplasia, or vertical gaze palsy. Patients will have ptosis and ophthalmoplegia; the severity can be variable. The pupil is almost invariably involved. Miosis is more common than mydriasis due to aberrant regeneration. Amblyopia can occur. Synkinetic movements, such as Marcus Gunn Jaw Winking, are common due to aberrant regeneration. Abberent regeneration can also occur in compressive third nerve palsies but is rare in ischemic third nerve palsy.

That finishes the oculomotor nerve. Now, let's revisit the multiple-choice questions and see their answers.

1. Which of the following statements about the oculomotor nerve nucleus complex is TRUE?

A) It lies in the pons at the level of the inferior colliculus

B) The superior rectus subnucleus supplies the ipsilateral eye

C) The medial rectus subnucleus is isolated and easily affected by lesions

D) The Edinger-Westphal nucleus provides parasympathetic fibers to the pupil and ciliary muscle

Answer: D – The Edinger-Westphal nucleus sends preganglionic parasympathetic fibers to the ciliary ganglion, supplying the pupillary sphincter and ciliary muscle for accommodation.

2. A lesion affecting the unilateral superior rectus subnucleus will cause which of the following findings?

A) Ipsilateral superior rectus palsy only

B) Contralateral superior rectus palsy only

C) Bilateral superior rectus palsy

D) No effect on the superior rectus

Answer: C – The superior rectus subnucleus is the only paired oculomotor subnucleus that supplies the opposite eye. Because the decussation of fibers to the superior rectus occurs within the oculomotor nuclear complex, the lesions affecting the nucleus may simultaneously involve the ipsilateral superior rectus subnucleus and the crossing fibers, resulting in bilateral superior rectus palsy.

3. Which of the following is TRUE regarding fascicular third nerve palsy?

A) It always presents with contralateral third nerve involvement

B) It resembles a peripheral third nerve palsy but can be associated with brainstem signs

C) It never involves the pupil

D) It is commonly caused by diabetic neuropathy

Answer: B – Fascicular lesions of the oculomotor nerve resemble peripheral third nerve palsy but often involve other brainstem structures like the red nucleus or superior cerebellar peduncle, helping in localization.

4. Which of the following is a key feature of cavernous sinus lesions affecting the oculomotor nerve?

A) Isolated third nerve palsy with pupillary sparing

B) Presence of Horner's syndrome due to sympathetic fiber involvement

C) No involvement of other cranial nerves

D) No associated pain

Answer: B – Cavernous sinus lesions often cause combined cranial nerve involvement (III, IV, V1, V2, VI) and Horner's syndrome due to sympathetic fiber disruption. Horner's syndrome helps to differentiate a cavernous lesion from a superior orbital fissure lesion. Painful ophthalmoplegia is a key feature when the lateral wall is involved.

5. Which condition is most likely to cause pupillary sparing in third nerve palsy?

A) Posterior communicating artery aneurysm

B) Cavernous sinus lesion

C) Ischemic third nerve palsy (diabetes)

D) Brainstem infarction involving the oculomotor nucleus

Answer: C – Diabetic third nerve palsy (ischemic) typically spares the pupil because parasympathetic fibers run peripherally in the nerve, while ischemia affects the core of the nerve.

That is all regarding the Oculomotor nerve. I hope you all enjoyed the episode. We will meet next month with the second episode of season 2, The Trochlear Nerve.

Thank you for listening to the 'Clinical Neurology with KD' podcast. We value your feedback, and it motivates us to keep podcasting. Please subscribe, rate, and review the podcast if you find it beneficial. You can follow the Neurology Teaching Club on Instagram, Facebook, or X for exclusive visuals related to this podcast. To receive new episodes and notes directly in your inbox, subscribe to our newsletter at neurologyteachingclub.com. Please note that the podcast and online content are meant for medical education only and should not be used to guide clinical decision-making or treatment. You can find more episodes on Apple Podcasts, Spotify, Amazon Music, or wherever you enjoy podcasts. This is KD signing off—until next time, spread knowledge!