18 Supranuclear and Internuclear disorders of eye movement

Where are the ocular motor nuclei for CN III, IV, and VI located?

• CN III oculomotor nuclear complex: midbrain, anterior to the cerebral aqueduct

• CN IV trochlear nucleus: pontomesencephalic junction, ventral to the aqueduct, caudal to CN III

• CN VI abducens nucleus: dorsal pons, immediately ventral to the facial nerve genu, forming the facial colliculus

What is unique about trochlear nucleus innervation?

Each trochlear nucleus innervates the contralateral superior oblique muscle.
High-yield point: CN IV fibers decussate before exiting, so a trochlear nuclear lesion affects the opposite superior oblique.

What are the two major functional outputs of the abducens nucleus?

The abducens nucleus contains:

1. Motor neurons that innervate the ipsilateral lateral rectus via CN VI

2. Interneurons that ascend in the contralateral MLF to activate the contralateral medial rectus subnucleus of CN III

This allows conjugate horizontal gaze.

What is the difference between supranuclear and internuclear ocular motor disorders?

• Supranuclear disorders: lesions above the ocular motor nuclei, involving control centers in the brainstem, cerebellum, or cerebral hemispheres

• Internuclear disorders: lesions of brainstem pathways that coordinate eye movements, especially connections such as the MLF

Why do internuclear lesions cause impaired conjugate gaze?

Internuclear lesions disrupt communication between ocular motor nuclei.
Classic example: an MLF lesion prevents the abducens nucleus on one side from activating the contralateral oculomotor medial rectus subnucleus, impairing coordinated horizontal eye movement.

What is the basic pathway for a leftward horizontal saccade?

A right frontal eye field initiates a leftward saccade by activating the left PPRF.
The left PPRF activates the left abducens nucleus, which then:

1. Activates the left lateral rectus via CN VI to abduct the left eye

2. Sends interneurons through the right MLF to the right oculomotor nucleus, activating the right medial rectus to adduct the right eye

What role do omnipause neurons play in horizontal saccades?

Omnipause neurons tonically inhibit burst neurons in the PPRF between saccades.
To generate a saccade, cortical eye fields inhibit omnipause neurons, which disinhibits the PPRF, allowing burst neurons to drive rapid eye movement.

Mechanism sequence:
FEF inhibits OPN → PPRF disinhibited → abducens nucleus activated → conjugate gaze

How does the abducens nucleus coordinate both eyes during horizontal gaze?

The abducens nucleus is the key horizontal gaze hub. It sends:

• CN VI motor fibers to the ipsilateral lateral rectus

• Internuclear fibers through the contralateral MLF to the contralateral CN III medial rectus subnucleus

What is the hallmark pattern of supranuclear ocular motor disorders?

Supranuclear ocular motor disorders affect some types of eye movements more severely than others.
The typical order of vulnerability is:

1. Saccades affected first and most severely

2. Other voluntary/pursuit movements variably affected

3. VOR affected last and least severely

Why is preservation of the VOR useful for localizing a supranuclear gaze disorder?

If voluntary gaze is impaired but the vestibulo-ocular reflex, or oculocephalic maneuver, is preserved, the lesion is likely supranuclear, because the ocular motor nuclei and final common pathways are still intact.

What happens with a frontal eye field lesion?

A frontal eye field lesion causes:

• Contralateral gaze palsy

• Acute deviation of the eyes toward the side of the lesion

What happens with a PPRF lesion?

A PPRF lesion causes:

• Ipsilateral horizontal gaze palsy

• Acute deviation of the eyes away from the side of the lesion

• Deficit is overcome by oculocephalic movements

How do PPRF and abducens nucleus lesions differ on oculocephalic testing?

• PPRF lesion: ipsilateral gaze palsy that can be overcome by oculocephalic movements

• Abducens nucleus lesion: ipsilateral gaze palsy that cannot be overcome by oculocephalic movements

What happens with an abducens nucleus lesion?

An abducens nucleus lesion causes:

• Ipsilateral horizontal gaze palsy

• Acute deviation of the eyes away from the side of the lesion

• Deficit is not overcome by oculocephalic movements

Mechanism: The abducens nucleus contains both:

1. CN VI motor neurons to the ipsilateral lateral rectus

2. Interneurons to the contralateral medial rectus subnucleus via the MLF

So a lesion prevents both eyes from looking toward the lesion.

What is the main function of the vestibulo-ocular reflex?

The VOR stabilizes vision during head movement.
It keeps the eyes fixed on a target during locomotion or head rotation by producing compensatory eye movements opposite the direction of head movement.

Key phrase: VOR enables clear vision during locomotion.

What is the basic pathway of the horizontal VOR?

Vestibular inputs project to the vestibular nuclei, then travel rostrally through the MLF to reach ocular motor nuclei.
For horizontal gaze, fibers pass through but do not synapse in the caudal PPRF, then ultimately synapse at the sixth nerve nucleus.

What sensory inputs contribute to the vestibular nuclei for VOR control?

Vestibular nuclei receive input from:

• Labyrinthine semicircular canals

• Otolith organs

• Visual system

• Somatosensory system

Why is the VOR spared longer than saccades in supranuclear disorders?

The VOR depends on brainstem vestibular pathways and ocular motor nuclei rather than voluntary cortical gaze commands.
Therefore, supranuclear lesions often impair saccades first, while VOR remains relatively preserved until more extensive disease.

What is Parinaud’s syndrome, and what eye movement pathway is primarily affected?

Parinaud’s syndrome, also called dorsal midbrain syndrome, is a supranuclear vertical gaze palsy caused by involvement of dorsal midbrain vertical gaze pathways, especially the riMLF.

What are the classic ocular signs of Parinaud’s syndrome?

Classic signs include:

• Supranuclear vertical gaze palsy

• Convergence-retraction nystagmus with attempted upward saccade

• Collier’s sign: lid retraction

• Mid-position pupils around 4 to 5 mm

• Light-near dissociation

What is light-near dissociation in Parinaud’s syndrome?

Light-near dissociation means the pupils respond poorly to light, but constrict better during near accommodation/convergence.

What is progressive supranuclear palsy, and who is typically affected?

Progressive supranuclear palsy, or PSP, is a progressive degenerative CNS disease that usually presents in the 6th to 7th decade.

Epidemiology:

• Older adults

• Male = female

What is often the first ocular sign of progressive supranuclear palsy?

The first ocular sign is often impaired voluntary downward saccades.

Progression:

1. Downward saccades impaired first

2. Other saccades become impaired

3. Pursuits become impaired

4. Eventually VOR may be lost

Why are oculocephalic movements initially preserved in PSP?

PSP initially affects supranuclear pathways, not the ocular motor nuclei or infranuclear pathways.

Therefore:

• Voluntary eye movements are impaired

• Oculocephalic reflexes/VOR are initially preserved

• Caloric testing can still produce tonic deviation early

What happens to eye movements late in progressive supranuclear palsy (PSP)?

Late in PSP, even the VOR is lost, resulting in complete binocular ophthalmoplegia.

This indicates progression beyond supranuclear control pathways to broader gaze system dysfunction.

What non-ocular features support a diagnosis of PSP?

PSP is associated with:

• Axial rigidity

• Dementia/cognitive impairment

• Progressive neurodegenerative course

How can visual symptoms in PSP sometimes be treated?

Visual symptoms may be helped with prism spectacles, especially when gaze limitation causes functional visual difficulty. Prisms treat symptoms, but they do not stop disease progression.

How does PSP illustrate the key principle of supranuclear ocular motor disorders?

PSP initially shows no defect in nuclear or infranuclear pathways, so reflex eye movements are preserved early.

Pattern:

• Voluntary saccades impaired first

• Oculocephalics/VOR preserved early

• VOR lost late

What is internuclear ophthalmoplegia, and what structure is lesioned?

Internuclear ophthalmoplegia, or INO, is caused by a lesion of the medial longitudinal fasciculus, MLF.

The MLF normally connects:

• Abducens nucleus, CN VI on one side
  to

• Contralateral medial rectus subnucleus of CN III

What is the classic eye movement abnormality in INO?

INO causes:

• Adduction paresis of one or both eyes

• Abducting nystagmus in the abducting eye

• Lesion is ipsilateral to the eye with adduction weakness

• Often associated with ipsilateral exotropia

How can you localize an INO lesion based on the affected eye?

The INO lesion is on the same side as the eye that fails to adduct.

Rule:
Weak adduction = ipsilateral MLF lesion

How do symptoms differ between mild and severe INO?

• Mild INO: transient diplopia or blur during saccades, often due to subtle adduction lag or abducting nystagmus

• Severe INO: more obvious diplopia due to increased adducting lag during saccades and pursuits

Why does INO cause diplopia?

INO causes diplopia because one eye has delayed or impaired adduction, so the two eyes are not aligned during horizontal gaze.

What are the most common causes of INO by age group?

• Younger patients: usually multiple sclerosis, often bilateral INO

• Older patients: usually stroke, often unilateral INO

What are other possible causes of INO besides MS and stroke?

Other causes include:

• Tumors

• Trauma

• Infection

• Degenerative disease

• Drug abuse or toxic/metabolic causes

But the most testable causes remain:
MS in younger patients, stroke in older patients.

What lesion causes one-and-a-half syndrome?

One-and-a-half syndrome is caused by a lesion involving both:

1. Ipsilateral abducens nucleus and/or PPRF

   • Causes horizontal gaze palsy toward the side of the lesion

2. Ipsilateral MLF

   • Causes INO in the involved eye

   • Produces adduction deficit of the ipsilateral eye

What eye movements remain intact in one-and-a-half syndrome?

The only preserved horizontal eye movement is abduction of the contralateral eye.

Example:
A left one-and-a-half syndrome causes:

• Neither eye can look left due to left PPRF/CN VI nucleus involvement

• Left eye cannot adduct on right gaze due to left MLF involvement

• Only the right eye can abduct on right gaze

Why can one-and-a-half syndrome be associated with facial nerve palsy?

One-and-a-half syndrome may involve the dorsal pons near the abducens nucleus, where fibers of the facial nerve, CN VII, loop around the abducens nucleus to form the facial colliculus.

Therefore, a nearby pontine lesion can cause:

• Horizontal gaze palsy

• INO

• Ipsilateral facial weakness

When does INO warrant MRI?

INO generally warrants an MRI, except in patients with a known diagnosis of multiple sclerosis where the INO is consistent with prior demyelinating disease.

Reason: INO localizes to the MLF in the brainstem, so imaging helps evaluate for causes such as stroke, demyelination, tumor, trauma, or infection.

What is the prognosis for recovery in INO?

Prognosis for recovery is generally good for both:

• Demyelinating INO, such as multiple sclerosis

• Vascular INO, such as stroke