Ocular motor cranial nerves
It is often said, “the eyes are the windows to the soul.” This beautiful literary quote is not exactly a scientifically provable statement... but science has shown us over the years that, our eyes are certainly the windows of our body, allowing us to view the world in which we live and everyone and everything contained within it.
The ability to see is accomplished using a combination of both sensory input from the eye (more specifically from the specialized cells of the retina), and motor output from the brain to the muscles around and attached to the eyes.
The muscles surrounding the eye are aptly named the extraocular muscles, and they allow the eyes to move, giving more control over what is seen and where. Without these muscles and the nerves that innervate them, the process of observation would be completely different: rather than just shifting one’s gaze, one would have to turn the whole head to look in any direction. Instead, these muscles allow us to quickly adapt without the necessity of having to engage in significantly effortful, obvious movements.
The following article focuses on these muscles, their functions, and the nerves that innervate them.
- Cranial nerves
- Oculomotor nerve (CN III)
- Trochlear nerve (CN IV)
- Abducens nerve (CN VI)
- Ocular motor nerves as parts of the corticobulbar tract
- Clinical notes
- Lesions of the MLF and/or PPRF
The nerves that innervate the extraocular muscles are among a group of nerves called the cranial nerves, which are so called because they arise in the brain and supply structures of the head and neck. There are a total of 12 cranial nerves (CN):
- the olfactory nerve (CN I)
- the optic nerve (CN II)
- the oculomotor nerve (CN III)
- the trochlear nerve (CN IV)
- the trigeminal nerve (CN V)
- the abducens nerve (CN VI)
- the facial nerve (CN VII)
- the vestibulocochlear nerve (CN VIII)
- the glossopharyngeal nerve (CN IX)
- the vagus nerve (CN X)
- the spinal accessory nerve (CN XI)
- the hypoglossal nerve (CN XII)
Of these, CN I, CN II, CN VII, CN VIII, CN IX and CN X play roles in special sensory functions (i.e. olfaction, vision, gustation, audition, and balance); CN V (all three branches, the ophthalmic, maxillary, and mandibular) and CN IX play roles in somatic sensory functions; and CN III, CN IV, CN V (the mandibular branch, V3, only), CN VI, CN VII, CN IX, CN X, CN XI, and CN XII are responsible for motor functions.
Of the cranial nerves with motor functions, CN III, CN IV, and CN VI are the ocular motor nerves, which provide innervation to the extraocular muscles.
Oculomotor nerve (CN III)
The oculomotor nerve originates in the midbrain, in the oculomotor nuclear complex. This complex is located at the level of superior colliculus near the midline. The oculomotor nerve fibers contain both somatic efferent fibers and special visceral efferent fibers, specifically autonomic parasympathetic fibers. These parasympathetic fibers originate from a group of neuron cell bodies in the midbrain called the Edinger-Westphal nucleus.
Somatic efferent component
Trajectory and innervation
These axons pass through the red nucleus and emerge from the ventral midbrain medial to the crus cerebri. The nerve fibers travel through the lateral wall of the cavernous sinus and split into small superior and large inferior divisions; then enter the orbit via the superior orbital fissure along with the trochlear nerve, the ophthalmic division of the trigeminal nerve (CN V1), and the abducens nerve.
The oculomotor nerve innervates the majority of extraocular muscles: the superior rectus and levator palpebrae superioris are innervated by superior division while inferior division innervate , medial, and inferior recti and the inferior oblique.
The superior rectus muscle originates at the superior part of the common tendinous ring above and lateral to the optic canal, and inserts on the superior surface of sclera approximately 8 mm from the limbus. Contraction of the superior rectus elevates, adducts, and medially rotates the eye, and as such is the main muscle responsible for upward gaze.
The inferior rectus muscle originates at the inferior part of the common tendinous ring below the optic canal, and inserts on the inferior surface of the sclera approximately 6 mm from limbus. Contraction of the inferior rectus depresses, adducts, and laterally rotates the eye, and as such it is the main muscle responsible for downward gaze.
The medial rectus muscle originates at the medial part of the common tendinous ring, medial to and below the optic canal, and inserts on the medial surface of the sclera. Contraction of the medial rectus adducts the eye, both medial recti act together for convergence.
The inferior oblique muscle originates on the medial floor of the orbit just behind the orbital rim, and attaches on the orbital surface of the maxilla lateral to the nasolacrimal groove. It inserts on the outer inferior surface of the eye. Contraction of the inferior oblique elevates, abducts, and laterally rotates the eye, allowing for upward, outward gaze.
The levator palpebrae superioris originates on the lesser wing of the sphenoid bone anterior to the optic canal and inserts on the anterior surface of the tarsal plate, with a few fibers attaching to the skin and superior conjunctival fornix. Contraction of the levator palpebrae superioris elevates the upper eyelid, opening the eye.
Visceral efferent component (parasympathetic)
The parasympathetic fibers originate from the Edinger-Westphal nucleus which is located in the midbrain. Preganglionic visceral motor axons leave the nucleus and course through the midbrain with somatic efferents both of which constitutes CNIII. Parasympathetic axons branch from the nerve to inferior oblique and terminate in the ciliary ganglion. Postganglionic axons leave the ciliary ganglion in the form of 6-10 short ciliary nerves which perforate the sclera and supply the cornea, choroid, iris, ciliary body and sclera.
Pupillary light reflex
The pretectal region of midbrain contributes to the circuit for the pupillary light reflex. This reflex has two main components, an afferent (sensory) component involving the optic nerve and an efferent (motor) component involving the oculomotor nerve.
The sequence begins with light-induced activation of retinal fibers (the afferent component of the reflex). These fibers synapse with neurons in pretectal region, which in turn project to the oculomotor nucleus. The preganglionic parasympathetic neurons from the Edinger-Westphal nucleus send axons via the oculomotor nerve to synapse with postganglionic neurons in the ciliary ganglion, which innervates the sphincter pupillae, constricting the pupil (the efferent component of the reflex).
Accommodation is adaptation of the eyes for near vision. It is obtained by increase in the curvature of the lens, pupillary constriction and convergence of eyes.
The parasympathetic fibers originating from the Edinger-Westphal nucleus also innervate the ciliary muscle. When this muscle contracts, it releases the suspensory ligament of the lens, which allows the lens to relax and increase its degree of curvature. The signals of Edinger-Westphal nucleus to sphincter like pupillary muscles result in the smaller pupil to sharpen the image on retina. Convergence of the eyes is brought about by both medial recti muscles supplied by somatic efferent component of the oculomotor nerve.
Trochlear nerve (CN IV)
The trochlear nerve originates from the trochlear nucleus which lies at the level of inferior colliculus in the tegmentum of the midbrain. It has only a somatic efferent component.
Axons arising from the nucleus course dorsally around the periaqueductal grey matter and cerebral aqueduct and cross the midline. The trochlear nerve is unique in that the axons of the cells within this nucleus cross over to the contralateral side before emerging from the dorsal surface of the caudal midbrain, just below the inferior colliculi. The nerve fibers travel through the cavernous sinus along with CN III,V1,V2 & VI. Within the sinus the trochlear nerve is lateral to the internal carotid artery. It leaves the sinus and enters the orbit via the superior orbital fissure, along with the oculomotor nerve, the ophthalmic division of the trigeminal nerve, and the abducens nerve. The nerve courses medially close to the roof of the orbit and reaches the superior oblique muscle to innervate it.
The superior oblique muscle originates on the body of the sphenoid superior and medial to the optic canal, follows the medial border of the roof of the orbit, and passes through a fibrocartilaginous structure called the trochlea. It inserts on the outer superior surface of the eye. Contraction of the superior oblique depresses, abducts, and medially rotates the eye, allowing for downward, outward gaze.
Abducens nerve (CN VI)
Abducens nerve contains only somatic efferent fibers to innervate only one muscle of the orbit, lateral rectus. The abducens nerve originates from cells in the abducens nucleus, which is located in the dorsomedial part of the posterior pons, pontine tegmentum, just ventral to the fourth ventricle.
The axons of the facial nerve loop around the abducens nucleus and form bulge in the floor of fourth ventricle called facial colliculus. The axons of the cells within this nucleus travel ventrally and emerge from the brainstem at the pontine-medullary border (junction of the pons & pyramid of medulla). It runs ventro-laterally in the subarachnoid space of posterior cranial fossa and penetrates the dura lateral to dorsum sellae of sphenoid bone. The nerve fibers travel forward between the dura and apex of the petrous temporal bone to enter he cavernous sinus. The nerve enters the orbit via the superior orbital fissure along with the oculomotor nerve, the trochlear nerve, and the ophthalmic division of the trigeminal nerve. The abducens nerve innervates the lateral rectus muscle.
The lateral rectus muscle originates at the lateral part of the common tendinous ring where it bridges the superior orbital fissure, and inserts on the lateral surface of the anterior aspect of the sclera. Contraction of the lateral rectus abducts the eye.
Ocular motor nerves as parts of the corticobulbar tract
The corticobulbar tract (otherwise known as the corticonulcear tract) is responsible for influencing the motor nuclei of a number of cranial nerves, including the:
- oculomotor (III)
- trochlear (IV)
- mandibular component of the trigeminal (V3)
- abducens (VI)
- facial (VII)
- glossopharyngeal (IX)
- vagus (X)
- spinal accessory (XI)
- hypoglossal (XII) nerves
The tract operates as a two-neuron sequence: upper motor neurons (UMNs) descending from the cortex to the CN nuclei are considered part of the corticobulbar tract, and synapse on the cell bodies of lower motor neurons (LMNs) which are located in the CN nuclei. The axons of LMNs are considered as part of the cranial nerves themselves, with their axons projecting via the cranial nerves to the muscles of the face, head, and neck.
Corticobulbar motor fibers arise from the frontal eye fields (a region in the caudal portion of middle frontal gyrus), motor cortex (the precentral gyrus), and somatosensory cortex (the postcentral gyrus) where they travel from the cortex through the internal capsule and to the CN nuclei in the brainstem.
Fibers originating from the frontal eye fields project to two regions: the rostral interstitial nucleus of the MLF (riMLF), known as the vertical gaze center; and in the paramedian pontine reticular formation (PPRF), the pontine horizontal gaze center. Fibers from these two gaze centers then project to the motor nuclei of the oculomotor, trochlear, and abducens cranial nerves. The frontal eye fields and parietal eye field also provide cortical input to the superior colliculus, which also provides input to the riMLF and PPRF. The riMLF is part of the medial longitudinal fasciculus (MLF), a bundle fibers that originate from the medial vestibular nucleus, reticular formation, and superior colliculus.
An important function of the MLF is to connect the abducens nucleus on one side of the brain with the oculomotor nucleus on the opposite side of the brain. This connection allows it to play a crucial role in synchronizing horizontal gaze. When the right abducens nucleus sends signals to the right lateral rectus muscle to contract, which pulls the right eye laterally to look right, it also sends signals via the MLF to the left oculomotor nucleus. These signals instruct the left oculomotor nucleus to innervate and thus simultaneously contract the left medial rectus muscle, which pulls the left eye medially so that it also points right at the same time the right eye does.
Oculomotor nerve palsy
Damage to the oculomotor nerve interrupts motor input to the majority of extraocular muscles, including most of the recti and the inferior oblique, as well as the levator palpebrae superioris, the sphincter pupillae, and the ciliary muscles. If the abducens and trochlear nerves are unaffected, the actions of the lateral rectus and superior oblique muscles respectively will be unopposed. As such, an isolated oculomotor nerve palsy presents as a “down-and-out” shifted eye, an eye directed inferiorly and laterally. An affected individual will also present with eyelid ptosis, or drooping of the eyelid. A fixed, dilated pupil (mydriasis) may also be present if the lesion affects the parasympathetic fibers within the oculomotor nerve.
Weber syndrome, otherwise known as medial midbrain syndrome, presents with a constellation of symptoms referred to as a superior alternating hemiplegia. It tends to result from a vascular lesion, typically of the paramedian branches of the posterior cerebral artery (PCA), and affects the medial region of the cerebral peduncle at the level of the superior colliculus and oculomotor nerve in the midbrain. Because of this, patients present with oculomotor paralysis on the same side of the lesion due to damage to the ipsilateral oculomotor nerve, and contralateral hemiplegia due to damage to the upper motor neuron fibers of the corticospinal tract within the crus cerebri.
Oculomotor deficits may include:
- dilation of the pupil
- lack of pupillary constriction in response to light (a fixed pupil)
- drooping of the eyelid(ptosis)
- deviation of the eye in the down and out direction.
Claude syndrome, otherwise known as a central midbrain lesion, is characterized by damage to the oculomotor nerve, the red nucleus, and cerebellothalamic fibers in the midbrain.
Damage to oculomotor nerve leads to ipsilateral paralysis of eye movement: this presents with the eye directed in the down and out eye position, with a dilated, fixed pupil and drooping lid.
Damage to the red nucleus and cerebellothalamic tract fibers is associated with contralateral ataxia and a cerebellar-associated tremor.
If the lesion extends to affect medial lemniscus and trigeminothalamic fibers, an affected individual may also present with a loss or reduction in position, vibration, and fine touch sensation in the contralateral arm and parts of the contralateral face respectively.
Benedikt syndrome describes a constellation of symptoms resulting from the presence of a large midbrain lesion that encompasses the regions damaged in both Weber syndrome and Claude syndrome. As such, deficits include contralateral hemiplegia due to damage to corticospinal fibers; ipsilateral eye movement paralysis with a fixed, dilated pupil and drooping lid due to oculomotor nerve damage; and cerebellar tremor and rubral ataxia due to damage to cerebellothalamic fibers and the red nucleus.
The presence of large or rapidly expanding supratentorial lesion (i.e. a lesion above the tentorium cerebelli), medial portion of the temporal lobe especially the uncal portion herniate across the tentorium. Herniating tissue puts pressure on the ipsilateral oculomotor nerve and crus cerebri. When this occurs, parasympathetic fibers within the oculomotor nerve are typically affected first: as such, an affected person may initially present with pupils that constrict uncharacteristically slowly in response to light. As herniation becomes more severe, however, ocular symptoms can progress to include fixed dilation of pupils and weakness and eventual paralysis of the oculomotor nerve and eye movement, resulting in deviation of the ipsilateral eye in the lateral and downward direction.
Weakness or even paralysis on the contralateral side of the body may also be observed due to compression of the corticospinal fibers within the ipsilateral crus cerebri. Combination of ipsilateral eye paralysis and contralateral hemiplegia makes this a superior alternating hemiplegia. Again, the contralateral hemiplegia is due to fact that the corticospinal fibers have not yet decussated to the side of the body that they are intended to innervate, so compression of corticospinal tract fibers prior to their decussation in the medulla leads to loss of motor innervation to the opposite side of the body.
Kernohan syndrome, or Kernohan phenomenon, occurs when uncal herniation results in a shift of the midbrain to the opposite side. Rather than affecting the oculomotor nerve and crus cerebri on the same side of the brain, shifting of the midbrain leads to stretching of the ipsilateral oculomotor nerve (i.e. on the side of the herniation) and compression of the contralateral crus cerebri against the opposing edge of the tentorium cerebelli, damaging the corticospinal fibers within. This situation presents with ipsilateral paralysis of the oculomotor nerve and ipsilateral hemiplegia.
Trochlear nerve palsy
Damage to the trochlear nerve interrupts motor input to the superior oblique muscle. If the oculomotor and abducens nerves are unaffected, the actions of the recti and inferior oblique muscles will be unopposed. Characteristic finding is a hypertropia due to superior oblique palsy and patient may have a head tilt towards the opposite shoulder to minimize the vertical diplopia which is a hallmark of an isolated trochlear nerve palsy. .
Abducens nerve palsy
Damage to the abducens nerve interrupts motor input to the lateral rectus muscle. If the oculomotor and trochlear nerves are unaffected, the actions of the medial, superior, and inferior recti and superior and inferior oblique muscles will be unopposed. Isolated nerve palsy presents with horizontal binocular diplopia with ipsilateral impaired abduction and esotropia (inward turning of eye).
Medial pontine syndrome
Median pontine syndrome typically occurs when there is occlusion of the paramedian branches of the basilar artery and subsequent ischemia of the medial aspect of the pons. This can result in damage to a number of structures, including: the corticospinal fibers, resulting in contralateral hemiplegia; the medial lemniscus, resulting in contralateral diminution or potential loss of vibration, proprioception, and fine touch sensation; abducens nucleus, or abducens nerve, resulting in ipsilateral paralysis of the lateral rectus muscle and subsequently diplopia, or a potential loss of conjugate gaze toward the side of the lesion via interruption of communication between the abducens nucleus of one side of the brain with the oculomotor nucleus on the opposite side. The involvement of medial longitudinal fasciculus may cause anterior internuclear ophthalmoplegia.
Lesions of the MLF and/or PPRF
If the medial longitudinal fasciculus (MLF) is lesioned between the motor nuclei of the abducens and oculomotor nerves in the midbrain, internuclear ophthalmoplegia—the inability to adduct the medial rectus muscle of one eye when the lateral rectus of the other eye is abducted for lateral gaze—can occur. This occurs due to the intricacies of connectivity between the abducens and oculomotor nuclei.
For example: the right abducens nerve innervates the right lateral rectus muscle. When the right abducens is activated, the right lateral rectus contracts and pulls the right eye so that it is abducted, with the pupil facing laterally (i.e. to the right). The abducens nucleus on the right side sends fibers across the midline to the left oculomotor nucleus via the MLF, instructing the left oculomotor nerve to innervate the medial rectus muscle in the left eye, facilitating synchronous movement of these muscles for rightward gaze. As such, an interruption in the MLF between the right abducens nucleus and the left oculomotor nucleus will block signals to the left eye to look right when the right eye looks right: in a patient with this lesion, the right eye will abduct to the right, but the left eye will be stationary, continuing to gaze forward.
Internuclear ophthalmoplegia is one of the characteristic signs associated with multiple sclerosis, an autoimmune demyelinating disease of the central nervous system. Other associated signs and symptoms include:
- hemisensory symptoms
- optic neuritis
- scanning speech
- intention tremor
These symptoms tend to be relapsing and remitting. The wide variability of symptoms reflects the potential of the disease at any time to damage any part of the brain or spinal cord. As such, the lesions are considered to have both temporal and spatial heterogeneity.
Lesions to the abducens nucleus and the paramedian pontine reticular formation (PPRF) can result not only in horizontal gaze palsies, but can also contribute to a condition called one-and-a-half syndrome. One-and-a-half syndrome is a combination of internuclear ophthalmoplegia with CN VI palsy. This occurs when a lesion affecting the abducens nucleus or PPRF also interrupts MLF fibers en route to the oculomotor nucleus on the same side (i.e. after they have crossed over from the opposite abducens nucleus).
For example: when the left abducens nucleus sends signals to the left lateral rectus to abduct, it also sends signals to the right oculomotor nucleus via the MLF. These signals instruct the oculomotor nucleus to send signals to medial rectus of the right eye to adduct simultaneously (so that both eyes look in the same direction). Damage to the MLF, connecting the abducens nucleus to the opposite oculomotor nucleus, can result in failure of this synchronous gaze. Thus, damage to the MLF between the left abducens nucleus and right oculomotor nucleus will present with loss of adduction in the right eye. When the PPRF or abducens nucleus is also damaged, this results in loss of lateral deviation of the ipsilateral eye as well as loss of communication with the opposite oculomotor nucleus. This means the ipsilateral eye cannot abduct, and the contralateral eye cannot adduct.
As such, a lesion that damages the right PPRF or right abducens nucleus along with the MLF on that side as it connects the left abducens nucleus to the right oculomotor nucleus will result in an inability to abduct (lateral rectus palsy) and adduct (medial rectus palsy) the right eye (the “one”), and an inability to adduct the left eye (the “half”).
Lateral pontine syndrome
Lateral pontine syndrome may be observed when there is occlusion of the long circumferential branches of the basilar artery and subsequent ischemia of the lateral aspect of the pons. This can result in damage to a number of structures, including:
- the middle and superior cerebellar peduncles, resulting in ataxia and gait instabilities, with a tendency to fall toward the side of the lesion
- the vestibular and cochlear nuclei and nerves, resulting in vertigo, nausea or vomiting, nystagmus, deafness, or tinnitus
- the facial motor nucleus, resulting in ipsilateral paralysis of the muscles of facial expression
- the trigeminal motor nucleus, resulting in ipsilateral paralysis of the muscles of mastication
- descending hypothalamospinal fibers, resulting in ptosis, miosis, and anhydrosis (a.k.a. Horner syndrome)
- the anterolateral system and parts of the spinal trigeminal tract and nucleus, resulting in contralateral loss of pain and temperature sensation in the body and ipsilateral loss of pain and temperature sensation in the face, respectively
- the PPRF, resulting in loss of conjugate gaze toward the side of the lesion
It should be noted that the exact constellation of symptoms observed will depend significantly on whether the lesion occurs in the rostral or caudal regions of the pons. Lesions of the lateral pons and their associated clinical presentations are often referred to as Gubler syndrome, or Miller-Gubler syndrome; but basilar pontine lesions specifically involving the trigeminal root may also be referred to as midpontine base syndrome.
Parinaud syndrome, otherwise known as gaze palsy, typically results from the presence of a tumor in the region of the pineal gland. A tumor in this location may arise from a variety of different types of cells, and as such may be a germinoma, astrocytoma, pineocytoma, or pineoblastoma.
As the tumor grows, it has the potential to occlude the cerebral aqueduct and put pressure on the superior colliculi. Occlusion of the cerebral aqueduct can lead to enlargement of the third ventricle and eventually hydrocephalus. Damage to superior colliculi is associated with upward gaze paralysis: this means an affected person cannot move the eyes up or down, a presentation sometimes referred to as sunset eye sign, setting-sun sign, or sunsetting of the eyes. Eventual impingement of the oculomotor and trochlear nuclei by the tumor can result in a more severe paralysis of eye movement; and if the medial longitudinal fasciculus (MLF) becomes involved, an affected person may also present with nystagmus.
A patient appears at your clinic complaining of diplopia, periorbital pain, and headache. The patient is an overweight, 64 year-old male with a medical history significant for hypertension and type II diabetes mellitus. Although he has been prescribed the antihypertensive medication lisinopril–an angiotensin-converting enzyme (ACE) inhibitor, a drug frequently prescribed to treat patients with co-occurring hypertension and diabetes–and antidiabetic medications including metformin (a drug which acts to decrease glucose production by the liver, decrease intestinal glucose absorption, and increase insulin sensitivity) and canagliflozin (an inhibitor of SGLT-2, a transporter otherwise responsible for reabsorbing glucose in the proximal tubule of the kidney), finger-stick testing quickly reveals that his disease is poorly controlled: the patient’s hemoglobin A1C (glycosylated hemoglobin) is revealed to be 8.0. Consistent with this finding, the patient reveals upon questioning that he lives alone and often misplaces or forgets to take his medications. Upon physical examination, you note that his left eyelid is drooping and his left eye points in the down and out direction. Pupillary light reflex testing reveals a symmetrical response of pupillary constriction.
This patient is presenting with a pupil-sparing oculomotor nerve palsy, characterized by the loss of somatic motor function (i.e. loss of function of the levator palpebrae superioris; medial, superior, and inferior recti; and inferior oblique muscles) with retention of special visceral afferent function of the constrictor pupillae muscle.
CN III palsy with sparing of the pupil is associated with ischemic neuropathy, which typically occurs secondary to microvascular disease. As such, it is frequently associated with hypertension, diabetes, or hyperlipidemia. Pupil-sparing CN III palsy, however, may also be associated with a compressive lesion, such as an aneurysm; although it should be noted that such space-occupying lesions can potentially progress to eventually affect the pupil as well. The presence of an aneurysm should be suspected when the patient does not have a history of diabetes, vascular disease, or other associated risk factors. Vasculitis, such as temporal (i.e. giant cell) arteritis, should also be considered as a potential etiology in older adults.
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