Impaired movement of the eyeballs

 

Oculomotor Nerve (n. oculomotorius, III pair of cranial nerves)

The oculomotor nerve (CN III) is a critical nerve for eye movement and pupillary function. Its motor nuclei are located on both sides of the midline in the rostral (upper) part of the midbrain, within the periaqueductal gray matter at the level of the superior colliculus. These nuclei innervate five of the seven extrinsic (external) muscles of the eyeball:

• Superior Rectus: Elevates the eye (primary action), also adducts and intorts.
• Inferior Rectus: Depresses the eye (primary action), also adducts and extorts.
• Medial Rectus: Adducts the eye (turns it inward towards the nose).
• Inferior Oblique: Elevates the eye when it is adducted, extorts, and abducts.
• Levator Palpebrae Superioris: The muscle that lifts the upper eyelid.

The oculomotor nerve nuclei also contain parasympathetic preganglionic neurons, forming the Edinger-Westphal nucleus. Axons from this nucleus travel with the oculomotor nerve to the ciliary ganglion, where they synapse. Postganglionic fibers then innervate the sphincter pupillae muscle (causing pupil constriction or miosis) and the ciliary muscle (involved in accommodation for near vision).

There is a specific organization of the supranuclear motor neuron groups within the oculomotor nuclear complex for each eye muscle. The fibers of the oculomotor nerve that innervate the medial rectus, inferior oblique, and inferior rectus muscles originate from the ipsilateral (same side) subnuclei. However, the subnucleus for the superior rectus muscle is located on the contralateral (opposite) side, meaning its fibers cross within the brainstem. The levator palpebrae superioris muscle is innervated by a central, unpaired caudal subnucleus of the oculomotor nerve complex, providing bilateral innervation to both eyelids.

 

Trochlear Nerve (n. trochlearis, IV pair of cranial nerves)

The motor neurons of the trochlear nerve (CN IV) form nuclei that are closely adjacent to the main part of the oculomotor nerve nuclear complex, located more caudally in the midbrain at the level of the inferior colliculus. The trochlear nerve is unique among cranial nerves in several ways: it is the smallest cranial nerve in terms of axon count, has the longest intracranial course, and is the only cranial nerve that exits from the dorsal aspect of the brainstem and decussates (crosses over to the opposite side) completely before emerging. The left nucleus of the trochlear nerve innervates the right superior oblique muscle of the eye, and the right nucleus innervates the left superior oblique muscle. The superior oblique muscle's primary actions are intorsion (inward rotation) of the eyeball, depression (especially when the eye is adducted), and abduction.

 

Abducens Nerve (n. abducens, VI pair of cranial nerves)

The motor neurons of the abducens nerve (CN VI) are located in the abducens nucleus in the caudal part of the pons, near the floor of the fourth ventricle. This nerve innervates the lateral (external) rectus muscle of the eye on the ipsilateral (same) side. The primary action of the lateral rectus muscle is abduction (turning the eye outward away from the nose).

All three oculomotor nerves (III, IV, and VI), after leaving the brainstem, traverse the subarachnoid space, pass through the cavernous sinus (a venous structure at the base of the skull), and enter the orbit through the superior orbital fissure to reach their respective extraocular muscles.

 

Supranuclear Control of Eye Movements

Clear, binocular vision and coordinated eye movements (conjugate movements, where both eyes move together in the same direction) are achieved through the precise, integrated activity of individual eye muscles. These movements are controlled by supranuclear gaze centers located in the cerebral cortex and brainstem, and their intricate connections. Functionally, there are five distinct supranuclear systems that provide different types of eye movements:

 

Saccadic (Rapid) Eye Movements

Saccades are rapid, conjugate eye movements that shift the fovea quickly from one point of interest to another in the visual field. Voluntary saccades (command saccades) primarily originate from the contralateral frontal eye field (FEF) in the frontal cortex (Brodmann area 8). Reflexive saccades, which occur in response to sudden peripheral visual stimuli that "irritate" the central retinal fovea, can originate from the occipital-parietal region of the brain (parietal eye field - PEF). These frontal and occipital control centers send projections, often bilaterally but with contralateral predominance, to supranuclear brainstem gaze centers. The activity of these brainstem centers is also influenced by the cerebellum (for accuracy and coordination) and the vestibular nuclear complex.

The paramedian pontine reticular formation (PPRF), located in the pons, is the brainstem center responsible for generating horizontal saccades. Simultaneous innervation of the ipsilateral lateral rectus muscle and the contralateral medial rectus muscle during horizontal eye movements is coordinated by the medial longitudinal fasciculus (MLF). The MLF connects the abducens nucleus (which controls the ipsilateral lateral rectus and also contains interneurons projecting to the contralateral oculomotor nucleus) to the subnucleus of the oculomotor complex responsible for innervating the contralateral medial rectus muscle.

For the initiation of vertical saccades, bilateral stimulation of the PPRF from cortical structures is required. The PPRF then transmits signals to supranuclear centers in the midbrain that control vertical eye movements. Such a supranuclear center includes the rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF), located in the pretectal area of the midbrain, and the interstitial nucleus of Cajal (INC).

 

Smooth Pursuit (Targeted) Eye Movements

Smooth pursuit movements allow the eyes to smoothly track a slowly moving object, keeping its image stabilized on the fovea. The cortical center for smooth pursuit is located primarily in the ipsilateral occipital-parietal region (PEF and motion-sensitive areas like MT/MST). Thus, the right occipital-parietal region controls smooth pursuit movements to the right. These pathways also involve the cerebellum and brainstem structures.

 

Vergence (Convergent) Eye Movements

Vergence movements are disconjugate movements where the eyes move in opposite directions to fixate on objects at different depths. Convergence (eyes turn inward) occurs when viewing a near object. The neural mechanisms controlling vergence movements are less completely understood but are known to involve neurons located in the reticular formation of the midbrain, surrounding the oculomotor nerve nuclear complex. These neurons project to the motor neurons innervating the medial rectus muscles of both eyes.

 

Gaze Holding Mechanisms (Neural Integrators)

Brainstem centers, often referred to as neural integrators, are responsible for maintaining the gaze in an eccentric (off-center) position after a saccade or pursuit movement. These centers effectively convert velocity signals (related to the speed of eye movement) from saccadic or pursuit systems into position signals (information about where the eyes should be held). For horizontal gaze holding, neurons with this property are located in the pons, near and caudal to the abducens nucleus (e.g., nucleus prepositus hypoglossi, medial vestibular nucleus). For vertical gaze holding, the interstitial nucleus of Cajal (INC) is a key structure.

 

Vestibulo-Ocular Reflex (VOR) and Eye Movements with Gravity/Acceleration

The coordination of eyeball movements in response to changes in head position, gravity, and acceleration is primarily carried out by the vestibular system through the vestibulo-ocular reflex (VOR). The VOR generates compensatory eye movements in the direction opposite to head movements, which helps to stabilize the visual image on the retina during motion. If the coordination of movements between both eyes is impaired (dysconjugate gaze), diplopia (double vision) develops, as images from an object are projected onto disparate (non-corresponding) areas of the two retinas.

In congenital strabismus or long-standing strabismus (non-paralytic or comitant strabismus), an imbalance in muscle function results in misalignment of the eyeballs. In such cases, particularly if onset is in early childhood, the brain may learn to suppress the image from one of the eyes to avoid diplopia. This suppression, if persistent, can lead to a decrease in visual acuity in the non-fixing or deviated eye, a condition known as amblyopia (sometimes referred to as "amblyopia ex anopsia" or lazy eye).

In paralytic strabismus, diplopia occurs as a direct result of paralysis or weakness of one or more extraocular muscles, usually due to damage to the oculomotor (III), trochlear (IV), or abducens (VI) cranial nerves or their nuclei.

 

Disorders of Eye Movement: Palsies of Ocular Muscles and Gaze

Paralysis or weakness affecting the external muscles of the eyeball can be categorized into three main types based on the pattern of involvement:

• Paralysis of individual extraocular muscles (due to ocular motor nerve lesions)
• Paralysis of conjugate (friendly) gaze movements (supranuclear gaze palsies)
• Mixed paralysis involving both gaze and individual eye muscles

 

Paralysis of Individual Extraocular Muscles (Ocular Motor Nerve Palsies)

Typical clinical manifestations arise with isolated injuries to the oculomotor (III), trochlear (IV), or abducens (VI) nerves.

• Complete Oculomotor Nerve (CN III) Palsy: Leads to:
  • Ptosis: Drooping of the upper eyelid due to paralysis (paresis) of the levator palpebrae superioris muscle.
  • Impaired Eye Movements: Difficulty or inability to move the eyeball upward, downward, and inward (adduction).
  • Exotropia and Hypotropia ("Down and Out" Position): The eye often deviates outward (laterally) and slightly downward due to the unopposed actions of the lateral rectus (CN VI) and superior oblique (CN IV) muscles.
  • Mydriasis: Pupil dilation due to paralysis of the sphincter pupillae muscle.
  • Loss of Pupillary Light Reflex: Lack of pupillary constriction in response to light (iridoplegia).
  • Accommodation Paralysis (Cycloplegia): Difficulty focusing on near objects.
  Isolated paralysis of the intrinsic muscles of the iris (sphincter pupillae) and ciliary body is termed internal ophthalmoplegia. Paralysis of only the external ocular muscles supplied by CN III is external ophthalmoplegia.

• Trochlear Nerve (CN IV) Palsy: Causes paralysis of the superior oblique muscle. This leads to:
  • Hypertropia: The affected eye deviates upward, especially when looking inward (adduction).
  • Excyclotorsion: Outward rotation of the eye.
  • Difficulty with Downward Gaze: Particularly when the eye is turned inward (e.g., reading or going downstairs). This paresis of downward gaze is most clearly manifested when the eyes are adducted.
  • Vertical or Oblique Diplopia: Double vision, which is often worse when looking down and in (contralateral to the affected eye).
  • Compensatory Head Tilt (Bielschowsky Head Tilt Test): Patients often tilt their head to the shoulder opposite the side of the palsied muscle to minimize diplopia. Tilting the head towards the palsied side worsens the hypertropia and diplopia.
• Abducens Nerve (CN VI) Palsy: Leads to paralysis of the lateral rectus muscle, which abducts the eyeball. This results in:
  • Esotropia (Convergent Strabismus): The affected eye deviates inward towards the nose due to the unopposed action (predominance of tone) of the normally functioning medial (internal) rectus muscle.
  • Inability to Abduct the Eye: Difficulty or inability to move the eye outward beyond the midline.
  • Horizontal Diplopia: Double vision, worse when looking towards the side of the palsied muscle.
  With incomplete paralysis of the abducens nerve, the patient may adopt a compensatory head turn towards the side of the affected abductor muscle to align the eyes and eliminate double vision by bringing the gaze into a field where the weakened lateral rectus muscle is less taxed.

The severity of the above symptoms in cases of damage to the oculomotor (III), trochlear (IV), or abducens (VI) nerves will depend on the completeness of the lesion (paresis vs. paralysis) and its specific location along the nerve's pathway (nucleus, fascicle, subarachnoid space, cavernous sinus, orbit).

 

Paralysis of Conjugate (Friendly) Gaze Movements (Gaze Palsies)

Conjugate gaze refers to the simultaneous movement of both eyes in the same direction (e.g., both eyes looking right). Gaze palsies result from lesions in the supranuclear pathways or brainstem gaze centers, not from isolated cranial nerve damage.

• Horizontal Gaze Palsy:
  • Acute damage to one of the frontal eye fields (FEF) in the cerebral cortex (e.g., due to a cerebral infarction/ischemic stroke) can lead to a transient paralysis of voluntary conjugate horizontal eye movements towards the opposite side. For example, a right FEF lesion causes difficulty looking voluntarily to the left. However, reflexive eye movements (e.g., oculocephalic reflex or "doll's eye maneuver," caloric stimulation) in all directions are typically preserved because the brainstem pathways are intact.
  • Unilateral damage to the paramedian pontine reticular formation (PPRF) at the level of the abducens nucleus causes a persistent ipsilateral horizontal gaze palsy (inability to look towards the side of the lesion) and loss of the oculocephalic reflex to that side. The oculocephalic reflex is a motor reaction of the eyes to irritation of the vestibular apparatus, elicited by passive head rotation ("doll's head and eyes" phenomenon) or caloric stimulation of the external auditory canal with cold water.
• Vertical Gaze Palsy (Supranuclear):
  • Damage to the rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF) in the anterior part of the midbrain and/or damage to the posterior commissure causes supranuclear vertical gaze palsy (Parinaud's syndrome). This syndrome often includes:
    • Impaired upward gaze (most common), sometimes also downward gaze.
    • Dissociated pupillary light-near response (Argyll Robertson-like pupils): sluggish or absent pupillary response to light, but a preserved (quick) pupillary reaction to accommodation (focusing on near objects) and convergence.
    • Convergence-retraction nystagmus (eyeballs retract and jerk convergently on attempted upgaze).
    • Eyelid retraction (Collier's sign).
    Parinaud's syndrome can occur with tumors in the pineal gland region, midbrain infarctions (ischemic strokes), multiple sclerosis, or hydrocephalus.
  • Isolated downward gaze palsy is rare. When it occurs, the most common cause is occlusion of penetrating midline arteries leading to bilateral infarctions of the midbrain.
  • Some hereditary extrapyramidal diseases (e.g., Huntington's disease, progressive supranuclear palsy - PSP) can cause progressive limitation of eye movements in all directions, especially voluntary saccades, often affecting vertical movements (particularly upward gaze in PSP) more severely or earlier than horizontal movements.

 

Mixed Paralysis of Gaze and Individual Eye Muscles (e.g., Internuclear Ophthalmoplegia)

A simultaneous combination of gaze paralysis and paralysis of individual muscles that move the eyeball in a patient usually signifies damage to the midbrain or pons, affecting both supranuclear pathways and cranial nerve nuclei or fascicles.

• Lesions in the lower parts of the pons involving the destruction of the abducens nucleus can lead to paralysis of rapid (saccadic) horizontal eye movements towards the side of the lesion (ipsilateral gaze palsy) combined with paralysis of the lateral (external) rectus muscle on the affected side (abducens nerve palsy).
• Internuclear Ophthalmoplegia (INO): Caused by a lesion of the medial longitudinal fasciculus (MLF), which connects the abducens nucleus of one side with the contralateral oculomotor nucleus (medial rectus subnucleus). This leads to various disorders of horizontal conjugate gaze:
  • Unilateral INO (e.g., due to a small brainstem infarct/ischemic stroke or demyelination): Results in impaired adduction (inward movement to the bridge of the nose) of the eye on the side of the MLF lesion when attempting to look towards the opposite side. This can manifest as complete paralysis of adduction (eye cannot move inward past the midline) or as moderate paresis (adduction lag, where the adducting eye moves slower than the abducting eye during saccades). Typically, abduction (outward movement) of the contralateral eye is preserved and often exhibits dissociated abducting nystagmus (nystagmus that occurs when the outwardly moving eye abducts, with the slow phase directed towards the midline, and rapid horizontal saccadic movements). An asymmetric vertical position of the eyeballs (skew deviation or hypertropia of the eye on the affected side) can also occur with unilateral INO.
  • Bilateral INO: Often occurs with demyelinating processes (e.g., multiple sclerosis), tumors, brainstem infarcts, or arteriovenous malformations. Bilateral INO leads to a more complete syndrome of eye movement disorders, manifested by bilateral paresis of adduction, often with dysfunction of vertical movements (especially upward gaze-evoked nystagmus), impaired smooth pursuit, and vestibulo-ocular reflex abnormalities. Impaired gaze along the vertical line, nystagmus on upgaze, and nystagmus on downgaze may be noted.
  Lesions of the MLF in the rostral (upper) parts of the midbrain are often accompanied by impaired convergence (converging movement of the eyes towards each other, towards the bridge of the nose).

 

Diagnosis of Impaired Eye Movements

A thorough diagnostic evaluation is essential to determine the cause of impaired eye movements:

1. Detailed Clinical History: Onset of symptoms (sudden or gradual), nature of diplopia (horizontal, vertical, oblique, worse in specific gazes), associated symptoms (pain, headache, ptosis, pupillary changes, weakness, sensory loss, vertigo, hearing loss), medical history (diabetes, hypertension, thyroid disease, myasthenia gravis, multiple sclerosis, trauma, infections).
2. Comprehensive Neurological and Neuro-ophthalmological Examination:
   • Assessment of visual acuity, visual fields, and pupillary responses (size, shape, reactivity to light and accommodation).
   • Evaluation of ocular alignment in primary position and all nine diagnostic positions of gaze to identify muscle weakness or restriction. Measurement of misalignment (e.g., using prism cover tests).
   • Assessment of saccades, smooth pursuit, vergence, and vestibulo-ocular reflexes.
   • Examination for ptosis, proptosis, and nystagmus.
   • Testing of other cranial nerves and full neurological assessment.
   • Forced duction test (to differentiate restrictive from paralytic strabismus).
3. Imaging Studies:
   • MRI of the Brain and Orbits (with and without contrast): Preferred modality for evaluating lesions affecting the brainstem, cranial nerves, cavernous sinus, orbit, and extraocular muscles. Specific sequences (e.g., FIESTA/CISS) can visualize cranial nerves. MR angiography (MRA) or venography (MRV) if vascular lesions or sinus thrombosis suspected.
   • CT Scan of the Head and Orbits: Useful for detecting bony abnormalities (fractures, tumors involving bone), acute hemorrhage, or calcification. CT angiography (CTA) for vascular lesions.
4. Laboratory Tests: Based on clinical suspicion, may include:
   • Blood tests for diabetes (glucose, HbA1c), thyroid function (TSH, T4), inflammatory markers (ESR, CRP), autoimmune markers (ANA, ANCA), acetylcholine receptor antibodies (for myasthenia gravis), Lyme serology, syphilis serology.
   • Lumbar puncture for CSF analysis if meningitis or inflammatory/demyelinating conditions are suspected.
5. Electrodiagnostic Tests:
   • Electromyography (EMG) of extraocular muscles (rarely performed, specialized centers).
   • Tensilon (edrophonium) test or ice pack test for suspected myasthenia gravis.

 

Treatment Principles for Impaired Eye Movements

Treatment is directed at the underlying cause of the eye movement disorder.

• Addressing the Primary Condition: E.g., control of diabetes or hypertension, treatment of thyroid eye disease, immunosuppression for myasthenia gravis or multiple sclerosis, antibiotics for infections, surgical removal or radiation for tumors, anticoagulation for cavernous sinus thrombosis.
• Management of Diplopia:
  • Observation: Some palsies (e.g., microvascular ischemic cranial nerve palsies) may resolve spontaneously over weeks to months.
  • Prisms: Fresnel prisms (press-on) or ground-in prisms in eyeglasses can help align images and relieve diplopia for small, stable deviations.
  • Occlusion: Patching one eye can eliminate diplopia but results in loss of binocular vision and depth perception. Alternating patching may be preferred.
  • Botulinum Toxin Injection: Can be injected into an overacting antagonist muscle to temporarily weaken it and improve alignment, particularly in acute palsies.
  • Strabismus Surgery: Surgical realignment of the extraocular muscles may be considered for persistent, stable diplopia that is not manageable with prisms, typically after 6-12 months of observation to allow for maximal spontaneous recovery.
• Supportive Care: E.g., eyelid crutches or ptosis surgery for severe ptosis in CN III palsy. Lubrication for exposure keratopathy if eye closure is impaired.
• Vision Therapy/Orthoptics: Exercises may be helpful for certain types of convergence insufficiency or accommodative problems, but generally not for paralytic strabismus.

 

Differential Diagnosis of Ophthalmoplegia/Gaze Palsy

The causes of impaired eye movements are numerous and depend on whether the lesion is infranuclear (cranial nerves III, IV, VI, or muscles), nuclear (brainstem nuclei), internuclear (MLF), or supranuclear (gaze centers/pathways).

Type of Deficit	Common Causes
Isolated CN III Palsy	Microvascular ischemia (diabetes, hypertension), compression (aneurysm - esp. posterior communicating artery, tumor), trauma, inflammation, congenital. (Pupil-sparing often ischemic; pupil-involving often compressive).
Isolated CN IV Palsy	Congenital, head trauma (most common acquired cause), microvascular ischemia, tumor (rare).
Isolated CN VI Palsy	Microvascular ischemia, increased intracranial pressure (non-localizing sign), trauma, tumor, inflammation (e.g., Gradenigo's syndrome), congenital (e.g., Duane syndrome).
Multiple Ocular Motor Nerve Palsies	Cavernous sinus pathology (tumor, inflammation, thrombosis, carotid-cavernous fistula), orbital apex syndrome, Miller Fisher syndrome (variant of Guillain-Barré), myasthenia gravis, meningitis, Wernicke's encephalopathy.
Horizontal Gaze Palsy	Pontine lesion (PPRF infarct/hemorrhage/tumor), FEF lesion (contralateral gaze palsy, often transient).
Vertical Gaze Palsy (e.g., Parinaud's)	Dorsal midbrain lesion (pineal tumor, stroke, hydrocephalus, MS), progressive supranuclear palsy (PSP), Niemann-Pick type C.
Internuclear Ophthalmoplegia (INO)	Multiple sclerosis (common in younger patients, often bilateral), brainstem stroke (common in older patients, often unilateral), tumor, trauma.
Restrictive Ophthalmopathy	Thyroid eye disease (Graves' ophthalmopathy), orbital tumor, orbital floor fracture with muscle entrapment, orbital inflammation (pseudotumor).
Myopathies affecting Extraocular Muscles	Chronic progressive external ophthalmoplegia (CPEO), myotonic dystrophy, mitochondrial myopathies.

 

Potential Complications and Prognosis

Complications primarily relate to the underlying cause and the effects of diplopia and impaired vision:

• Persistent diplopia impacting daily activities (reading, driving).
• Amblyopia in children if strabismus is not corrected.
• Abnormal head postures (torticollis) to compensate for diplopia.
• Corneal exposure and damage if ptosis or lagophthalmos is severe.
• Complications from the underlying neurological or systemic disease.

The prognosis depends on the etiology. Microvascular ischemic palsies often recover spontaneously. Traumatic palsies have variable recovery. Palsies due to tumors or aneurysms depend on the successful treatment of the primary lesion. Chronic or progressive conditions may lead to permanent deficits.

 

When to Consult a Neurologist or Neuro-ophthalmologist

Any new onset of double vision, drooping eyelid, pupillary abnormality, or noticeable restriction in eye movement warrants prompt medical evaluation. Consultation with a neurologist and/or a neuro-ophthalmologist (an ophthalmologist or neurologist specializing in the interface of eye and brain disorders) is crucial to:

• Determine the precise nature and cause of the eye movement disorder.
• Rule out serious or life-threatening underlying conditions (e.g., aneurysm, tumor, stroke).
• Initiate appropriate diagnostic investigations.
• Develop a comprehensive management plan.

Sudden onset of painful ophthalmoplegia, especially with pupillary involvement or associated neurological symptoms, should be considered a medical emergency.