The Abducens nerve

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

Chapters

• 0:00 Intro
• 1:03 Pre-test MCQs
• 2:28 Anatomy
• 4:56 Clinical features
• 5:40 Localisation of nuclear lesions
• 6:05 Mobius syndrome
• 6:32 Duane retraction syndrome
• 7:38 Foville syndrome
• 7:58 Fascicular lesion
• 8:44 Subarachnoid space lesions
• 9:55 Clivus lesions
• 10:20 Petrous apex and Dorellos canal lesions
• 11:18 Cavernous sinus and Superior orbital fissure lesions
• 12:24 Orbital lesions
• 12:43 Ischemic abducent palsy
• 13:16 Convergence spasm
• 13:47 Divergence insufficiency
• 14:07 Thalamic esotropia
• 14:41 Multiple ocular motor nerve palsy
• 15:08 Miller Fischer syndrome
• 15:48 Wernicke encephalopathy
• 16:36 Ophthalmoplegic migraine
• 17:20 Tolosa Hunt syndrome
• 18:12 Carotid cavernous fistula
• 19:42 Post-test MCQs
• 22:00 Outro

Transcript

In this session, we will discuss the abducens nerve. As usual, we will begin with the pre-test multiple-choice questions (MCQs).

1. What structure forms the roof of Dorello's canal?

A. Petrous temporal bone

B. Posterior clinoid process

C. Gruber's ligament

D. Falx cerebri

2. Which syndrome features abducens palsy, facial pain, and ear discharge?

A. Foville syndrome

B. Gradenigo syndrome 

C. Millard-Gubler syndrome

D. Godtfredsen syndrome

3. A lesion in which location is most likely to cause bilateral sixth nerve palsy with twelfth nerve involvement?

A. Cavernous sinus

B. Clivus 

C. Midbrain

D. Orbit

4. In a patient with sixth nerve palsy with Horner's syndrome, which feature best differentiates a cavernous sinus lesion from a pontine lesion?

A. Presence of abduction deficit

B. Distribution of facial sweating 

C. Involvement of the medial rectus

D. Conjugate gaze palsy

5. Which clinical scenario strongly suggests divergence insufficiency rather than an isolated sixth nerve palsy?

A. Esotropia at near and distance

B. Adduction deficit on duction testing

C. Full ductions with esotropia only at a distance 

D. Sudden onset diplopia with medial rectus overaction

Anatomy

The abducens nerve supplies a single muscle, the ipsilateral lateral rectus, which abducts the eye. The abducens nucleus is situated in the mid to lower dorsal pontine tegmentum, separated from the fourth ventricle by the genu of the facial nerve, which forms the facial colliculus. The nucleus consists of somatic motor neurons. The sixth cranial nerve nucleus contains motor neurons that give rise to the sixth nerve's fascicle and interneurons that give rise to the axons in the contralateral medial longitudinal fasciculus that innervate the contralateral medial rectus subnucleus of the third cranial nerve. Thus, the sixth cranial nerve nucleus mediates the ipsilateral conjugate horizontal eye movements as well. The fascicle of the abducens nerve moves forward through the pontine tegmentum close to the parapontine reticular formation after exiting the nucleus. It lies medial to the facial nerve fasciculus and adjacent to the medial lemniscus and the corticospinal tract. The abducens nerve leaves the brainstem in the horizontal sulcus between the pons and the medulla lateral to the corticospinal bundle.

In the subarachnoid space, the abducens nerve crosses the internal auditory artery and ascends the clivus in the prepontine cistern to reach the petrous apex. Then, it pierces the dura at the dorsum sella and traverses the Dorello canal between the posterior clinoid process and the petrous apex. Dorello'scanal is the invagination of the dura in the petroclival region from the petroclival entrance point to the posterior end of the cavernous sinus. The petrosphenoidal ligament, otherwise known as Gruber'sligament, forms the roof of the canal. The petrous temporal bone forms the floor of the canal. The Dorello's canal is a passageway for the abducens nerve from the brainstem to the cavernous sinus. It is a potential site of the abducens nerve entrapment during trauma and raised intracranial pressure.

In the cavernous sinus, the abducens nerve lies lateral to the internal carotid artery and medial to the ophthalmic division of the trigeminal nerve. The nerve lies below and medial to the oculomotor nerve. The abducens nerve is the only nerve that lies in the lumen of the cavernous sinus. Others are in the wall of the sinus. The pupil's sympathetic fibers, from their course from the peri carotid plexus to the ophthalmic division of the trigeminal, will travel a few millimeters through the abducens nerve in the cavernous sinus. The abducent nerve enters the orbit through the superior orbital fissure and the annulus of Zinn and supplies the lateral rectus.

Clinical features

Patients with abducens nerve palsy will have binocular diplopia, with horizontally separated images, more when looking at a distance and in the direction of the weak muscle. There will be limited abduction in the eye of the involved side, and the resting eye will be in an adducted position. This esotropia will increase when looking at the side of the lesion. In patients with mild abducens weakness, the esophoria detected by a cover-uncover test on looking to the paretic side may be the only sign of abducens palsy, as their range of movements may be normal. In these patients, the misalignment is concealed by the brain's fusional mechanism and becomes apparent only when binocular vision is disrupted.

Localization of the sixth cranial nerve palsy.

Nuclear lesion

A nuclear sixth nerve palsy produces a horizontal gaze palsy to the same side rather than an isolated lateral rectus palsy, as the nucleus contains interneurons that supply the opposite medial rectus through the MLF. The abducens nucleus lesion in early life will result in Mobius syndrome and Duane retraction syndrome.

Mobius syndrome

Most patients have bilateral nuclear sixth nerve palsy. The most common ocular motor abnormality is bilateral horizontal gaze palsy. They may also have additional bilateral facial diplegia and other cranial nerve palsies, including the ninth, tenth, and twelfth. The long tracts can also get involved, producing general motor disability and incordination. It is a disorder of rhombencephalic maldevelopment.

Duane retraction syndrome

Duane retraction syndrome is characterized by the narrowing of the palpebral fissure and retraction of the globe on adduction. There are three types.

Type 1: Abduction is limited, while adduction is normal.

Type 2: Impaird adduction with normal abduction.

Type 3: Abduction and adduction are both impaired.

The abducens nerve is absent in type 1 and, in some cases, in type 3. It is congenital, caused by the anomalous innervation of the lateral rectus by the inferior division of the oculomotor nerve. This results in simultaneous contraction of the medial and lateral rectus on attempted adduction, resulting in the globe's retraction. The patients often don't have diplopia or esotropia in primary gaze. They also usually don't develop ampliopia. All types show vertical deviation of the adducting eye through upshoots or downshoots during horizontal gaze. It is more common in females and affects the left eye more than the right eye, but it can be bilateral. It can rarely occur with acquired causes like pontine glioma and following surgery for orbital cavernous hemangioma.

An infarct in the anterior inferior cerebellar artery (AICA) can lead to Foville syndrome, which affects the dorsal pontine tegmentum. This syndrome features ipsilateral horizontal gaze palsy resulting from involvement of the abducens nucleus, facial palsy due to damage to the fascicle of the seventh cranial nerve, and contralateral hemiparesis.

Fascicular lesion

An anterior pontine paramedian lesion can spare the abducens nucleus and involve the fasciculus. It is commonly associated with the ipsilateral facial nerve and contralateral hemiparesis, a condition known as Millard-Gubler syndrome. Sometimes, a small lesion in the pons can involve the abducens fascicle alone, resulting in isolated sixth cranial nerve palsy. Nuclear and fascicular lesions can have associated long tract signs like ataxia, Horner's syndrome, and hemiparesis.The fifth, seventh, and eighth cranial nerves can also get involved in these cases. 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

Lesions affecting the abducens nerve in the prepontine cistern may compress the ipsilateral corticospinal bundles, leading to contralateral hemiparesis and ipsilateral sixth nerve palsy. Compression of the trigeminal nerve can cause ipsilateral facial pain. Lesions in the subarachnoid space can cause unilateral or bilateral sixth cranial nerve palsy. Any cause of raised intracranial pressure can cause abducent palsy. CN VI palsies are the most common and classic false localizing signs. They are nonspecific and do not necessarily relate anatomically to the central nervous system pathology that produces them. For example, a frontal lobe mass lesion may be the cause of raised ICT that causes the sixth nerve palsy. We assume that the pathology is somewhere in the course of the sixth cranial nerve, when it is in the frontal lobe, nowhere near the sixth cranial nerve. That is why it is called a false localizing sign. Both idiopathic intracranial hypertension and hypotension can cause sixth nerve palsy. All cases require imaging, ideally a contrast-enhanced MRI and CSF study if the imaging is normal. Cerebellopontine angle lesions can involve the abducens nerve.

Clivus

Combined sixth and twelfth cranial nerve palsy usually suggests a clivus lesion. It is called Godtfredsen syndrome, and the etiology is usually ominous, like nasopharyngeal carcinoma or clival metastasis. Rarely subarachnoid pathologies can also produce this syndrome. Both sixth nerves lie very close to each other at the clivus. Lesions here can also cause bilateral sixth nerve palsy. 

Petrous apex and Dorellos canal

Based on neurologic findings alone, it may be challenging to determine whether the nerve has been injured within the subarachnoid space or in its petrous portion in the Dorello canal. Associated trigeminal nerve involvement is more likely if the lesion is in the petrous portion. Other clinical findings may point to disease in the petrous bone, such as an ear discharge from chronic otitis media or mastoiditis and deafness. An infectious or neoplastic process that spreads to the tip of the petrous bone can lead to Gradenigo syndrome. This syndrome features the triad of abducens nerve paralysis, facial pain, and ear discomfort or discharge. Additionally, trauma, inferior petrosal sinus thrombosis, vascular malformations, aneurysms, and tumors may also cause injury to the nerve at this location. Increased intracranial pressure often leads to dysfunction of the abducens nerve due to stretching the nerve over the petrous tip, as the heightened pressure pushes the brainstem attachments inferiorly.

Cavernous sinus and Superior orbital fissure

The involvement of other ocular motor nerves, retro-orbital pain, and Horner's syndrome suggest a cavernous sinus lesion. Without Horner's syndrome, it is impossible to clinically differentiate a cavernous lesion from a superior orbital fissure lesion. The sympathetic fibers travel with the abducens nerve for a short distance in the cavernous sinus. Unilateral abducent nerve palsy with Horner's syndrome localizes to the cavernous sinus, called Parkinson's syndrome. A pontine lesion can also produce sixth nerve palsy with Horner's syndrome. However, the cavernous lesion causes a postganglionic Horner's syndrome with the absence of sweating confined to the forehead. In contrast, in central Horner's syndrome, due to a pontine lesion, sweating is affected over the entire face. Trigeminal nerve sensory loss in V2 distribution with abducent palsy can occur due to nasopharyngeal carcinoma arising in the fossa of Rosenmuller and extending into the foramen lacerum. The etiologies of the cavernous and the superior orbital fissure lesions are the same and include infective, inflammatory, and neoplastic causes.

Orbit

The sixth cranial nerve can be damaged inside the orbital cavity to produce lateral rectus palsy. Proptosis, chemosis, and optic nerve involvement may also be present, along with other ocular motor nerve involvement. Trauma, tumors, and inflammatory processes can cause abducens weakness in the orbit.

Ischemic abducent palsy

Vasculopathy is the most common cause of isolated sixth cranial nerve palsy. The nerve can be involved anywhere along its course. Along with diabetes, patients can have other vascular risk factors like hypertension, dyslipidemia, etc. The sixth nerve palsy can evolve over one week and usually recover spontaneously over three to six months. Recurrence is not uncommon. Older people with headaches should undergo evaluation for giant cell arteritis.

Other causes of abduction impairment.

Convergence spasm

Convergence spasm causes esotropia on lateral gaze and can be mistaken for sixth cranial nerve palsy. It is a functional disorder caused by voluntary convergence interrupting the lateral gaze. When the patient looks laterally, the sudden convergence stops the abducting eye midway, giving a feeling of lateral rectus palsy. The associated pupillary constriction is the clue that differentiates a convergence spasm from lateral rectus palsy. It can rarely be caused by midbrain compression.

Divergence insufficiency

These patients have impaired abduction and esotropia when looking at a distance. They, however, have full abduction on duction testing. Patients have a horizontal, comitant, uncrossed diplopia at far while near vision is normal. It can develop as an isolated entity in an otherwise healthy person.

Thalamic esotropia

Acute esotropia can occur in patients with contralateral thalamic infarct. Acute thalamic hemorrhage can cause bilateral asymmetric esotropia with a severity more on the contralateral side. The esotropia is due to supranuclear disinhibition of the convergence pathway. 

Other causes of abduction impairment include medial rectus entrapment in orbital fractures, Myasthenia gravis, orbital pseudotumor, and thyroid ophthalmopathy. Acquired esotropia can occur as an initial manifestation of cerebellar disease.

Multiple ocular motor nerve palsy

Multiple ocular motor nerve palsy can occur in lesions involving the brainstem, subarachnoid space, cavernous sinus, superior orbital fissure, or orbit. Lesions involving the neuromuscular junction, like ocular myasthenia, and muscle disease, like progressive external ophthalmoplegia, can also affect the extraocular muscles. We will discuss a few common disorders involving multiple extraocular nerves.

Miller Fischer syndrome

It is a variant of GBS characterized by areflexia, ophthalmoplegia, and ataxia. Most of these patients show anti-GQ1b ganglioside positivity. The third, fourth, and sixth cranial nerves contain a higher concentration of GQ1b in their ganglioside composition, making them vulnerable. Patients can have complete external ophthalmoplegia, including bilateral ptosis. Pupillary involvement is rare. A nerve conduction study reveals demyelinating neuropathy, and the cerebrospinal fluid will show albuminocytological dissociation. Patients respond well to IVIG/ plasma exchange.

Wernicke encephalopathy

Wernicke encephalopathy is characterized by the triad of confusion, ophthalmoplegia, and ataxia and is due to thiamine deficiency. Alcoholics, hyperemesis gravidarum, dialysis patients, cancer patients, and malnutrition due to any cause can produce this syndrome. Ocular findings can range from gaze-evoked nystagmus to total ophthalmoplegia. The ocular motor deficits in Wernicke encephalopathy arise from selective neurotoxic damage to brainstem nuclei and cerebellar pathways critical for gaze control, driven by thiamine-dependent metabolic failure. Prompt intravenous thiamine replacement (500 mg TID) reverses ocular motor deficits within hours to days. Delayed treatment risks progression to Korsakoff syndrome, characterized by irreversible memory impairment.

Ophthalmoplegic migraine

Ophthalmoplegic migraine causes painful ophthalmoplegia, which usually starts in the first decade of life. The oculomotor nerve is commonly involved, though isolated trochlear or multiple ocular motor nerves can also get involved. Patients will have a history of typical migraine attacks. The third nerve palsy reaches maximum as the headache subsides and can last for one to four weeks. Some patients can have partial third nerve palsy. It is a diagnosis of exclusion, and a detailed evaluation is necessary to rule out other causes. Patients are usually asymptomatic between attacks. MRI of the brain may show enhancement of the cranial nerves. Steroids are the mainstay in the treatment.

Tolosa Hunt syndrome

It causes recurrent painful ophthalmoplegia due to idiopathic granulomatous inflammation of the cavernous sinus, superior orbital fissure, or the orbit. The cardinal feature is retro-orbital pain, accompanied by palsy of the third, fourth, and sixth cranial nerves. Other cranial nerves, including the fifth and the seventh, can be involved rarely. MRI shows focal enhancement of the cavernous sinus. The differentials include infection, vasculitis, and neoplasm. CSF study and contrast imaging should be done in all cases to rule out alternate diagnoses. Steroids are the first line of treatment, and pain usually responds within 72 hours, which also supports the diagnosis. The ophthalmoplegia improves over weeks. Around 40% of the cases can have a recurrence. Refractory cases need immunosuppression and radiation.

Carotico cavernous fistula

Carotid cavernous fistula (CCF) is an abnormal vascular connection between the internal carotid artery (ICA), external carotid artery (ECA), or their branches, and the cavernous sinus. They are classified as direct or high-flow CCFs if they arise from a direct connection between the intracavernous carotid artery and the cavernous sinus. They are called indirect, low-flow, or dural CCFs if they result from indirect communication between the cavernous sinus and branches of the internal or external carotid artery within the adjacent dura. Traumatic CCF accounts for 70% of the cases. Spontaneous CCF accounts for 30% of the cases and is usually due to a rupture of the internal carotid aneurysm. Clinical manifestations include pulsatile tinnitus, conjunctival injection, proptosis, and ophthalmoplegia due to cranial nerve three, four, and six compression. Vision loss may occur from ocular ischemia or glaucoma. Diagnosis requires neuroimaging. CT/MRI detects proptosis, superior ophthalmic vein enlargement, and cavernous sinus abnormalities, while digital subtraction angiography (DSA) confirms fistula anatomy and flow dynamics. Treatment prioritizes endovascular embolization via transarterial or transvenous routes to occlude the fistula, preserving internal carotid artery patency. Corticosteroids may alleviate inflammation pre-intervention. Untreated CCFs risk vision loss, cerebral ischemia, or hemorrhage from cortical venous reflux. 

Now, let us discuss the post-test multiple-choice questions.

1. What structure forms the roof of Dorello's canal?

A. Petrous temporal bone

B. Posterior clinoid process

C. Gruber's ligament

D. Falx cerebri

Answer C. Gruber's ligament

Explanation: Gruber's ligament (also known as the petrosphenoidal ligament) forms the roof of Dorello's canal, through which the abducens nerve passes.

2. Which syndrome features abducens palsy, facial pain, and ear discharge?

A. Foville syndrome

B. Gradenigo syndrome 

C. Millard-Gubler syndrome

D. Godtfredsen syndrome

Answer B. Gradenigo syndrome

Explanation: Gradenigo syndrome is classically a triad of abducens nerve palsy, facial pain (due to trigeminal involvement), and ear discharge, usually due to petrous apex pathology (e.g., petrositis).

3. A lesion in which location is most likely to cause bilateral sixth nerve palsy with twelfth nerve involvement?

A. Cavernous sinus

B. Clivus 

C. Midbrain

D. Orbit

Answer B. Clivus

Explanation: A clival lesion may involve both abducent nerves (as they run near each other over the clivus) and the hypoglossal nerve, causing Godtfredsen syndrome.

4. Which feature best differentiates a cavernous sinus lesion from a pontine lesion in sixth nerve palsy with Horner's syndrome?

A. Presence of abduction deficit

B. Distribution of facial sweating 

C. Involvement of the medial rectus

D. Conjugate gaze palsy

Answer B. Distribution of facial sweating

Explanation: Cavernous sinus lesions cause postganglionic Horner's syndrome, with sweating spared except for the forehead, while pontine lesions (central Horner's) affect entire facial sweating.

5. Which clinical scenario strongly suggests divergence insufficiency rather than an isolated sixth nerve palsy?

A. Esotropia at near and distance

B. Adduction deficit on duction testing

C. Full ductions with esotropia only at a distance 

D. Sudden onset diplopia with medial rectus overaction

Answer C. Full ductions with esotropia only at a distance

Explanation: In divergence insufficiency, ocular motility is normal on duction, but esotropia is present only when viewing distant objects, not near. This helps differentiate it from true lateral rectus palsy.