Eye Movements and Pupillary Control
Anatomical and Clinical Review
- Extraocular Muscles – cause the eyes to move within the orbits
- Internal Ocular Muscles – control pupillary size and accommodation
Two Levels of Disorders and Pathways
- Nuclear and Infranuclear Pathways: involve brainstem nuclei of CN III, IV, and VI; the peripheral nerves arising from these nuclei; and the eye movements muscles
- Supranuclear Pathways: involve brainstem and forebrain circuits that control eye movements through connections with the nuclei of CN III, IV, and VI
Extraocular Muscles, Nerves, and Nuclei
| Six Extraocular Muscles | Innervation |
| Lateral rectus (abduction) | CN VI (abducens) – moves eye toward ear |
| Medial rectus (adduction) | CN III (oculomotor – inferior division) moves eye towards nose |
| Superior rectus (elevation and intorsion) | CN III (oculomotor – superior division) |
| Inferior rectus (depression and extorsion) | CN III (oculomotor – inferior division) |
| Superior oblique (depression and intorsion) | CN IV (trochlear) |
| Inferior oblique (elevation and extorsion) | CN III (oculomotor – inferior division) |
Muscles 1 – 4 are responsible for horizontal and vertical eye movements; muscles 5 & 6 are responsible for torsional movements
Other Eye Muscles
- Levator Palpebrae Superior: elevates eyelid; innervated by superior division of CN III
- Pupillary Constrictor Muscle: makes pupil smaller
- Pupillary Dilator Muscle: makes pupil larger
- Ciliary Muscle: adjusts thickness of lens in response to viewing distance
A Few Other Points
- The parasympathetic fibers controlling pupil constriction are susceptible to compression from aneurysms, particularly arising from the nearby posterior communicating artery
- Unilateral weakness of the levator palpebrae superior, or unilateral papillary dilation, cannot arise from unilateral lesions of the oculomotor nucleus
- Oculomotor nucleus lesions affect the contralateral superior rectus (further explanation in text, p. 533)
- Trochlear nerves are only cranial nerves to exit brainstem dorsally and in a completely crossed fashion; they are susceptible to compression from cerebellar tumors and to shear injury from head trauma
- Abducens nerve is highly susceptible to downward traction injury produced by elevated intracranial pressure
Diplopia
Primary Causes
- Mechanical problems (e.g., orbital fracture with muscle entrapment)
- Disorders of the extraocular muscles (e.g., thyroid disease, orbital myositis)
- Disorders of the neuromuscular junction (e.g., myasthenia gravis)
- Disorders of CN III, IV, VI, and their central pathways
Of Interest: Monocular diplopia or polyopia (3 or more images) can be caused by ophthalmological disease, d/o of visual cortex, or psychiatric conditions, but not by eye movement abnormality.
Movement Disorders
- Dysconjugate gaze: results from improperly working extraocular muscle and causes diplopia
- Exotropia: abnormal lateral deviation of one eye
- Esotropia: abnormal medial deviation of one eye
- Hypertropia: abnormal vertical deviation of one eye
- Phoria: mild weakness present only with one eye covered (as in, exophoria)
Of Interest: In young children, because visual pathways are still developing, congenital eye muscle weakness can produce strabismus (dysconjugate gaze) that over time suppresses one of the images, resulting in amblyopia (decreased vision in one eye). Early intervention is essential.
Oculomotor Palsy (CN III)
Complete disruption of CN III causes paralysis of all extraocular muscles except lateral rectus and superior oblique (i.e., some abduction and some depression/intorsion) —> eye lies in a “down and out” position; also upper lid is closed because of levator palpebrae superior paralysis, and pupil is dilated and unresponsive to light (due to parasympathetic fibers running with CN III)
Common Causes
- Diabetic neuropathy
- Head trauma (due to shearing forces)
- Compression of nerve by intracranial aneurysms, especially those arising from Pcomm
- Compression of nerve by herniation of the medial temporal lobe over the edge of the tentorium cerebelli
- Ophthalmoplegic migraine in children
Of Interest: Third nerve palsy should raise high index of suspicion for aneurysm; they often cause a painful oculomotor palsy that involves the pupil. Complete CN III palsy sparing the pupil is not an aneurysm, but usually caused by diabetes.
Trochlear Palsy (CN IV)
- Trochlear nerve palsy produces depression and intorsion, therefore, there is a vertical diplopia
- CN IV palsy confirmed by following four steps (Bielschowsky three step test plus the “missing step”)
- Affected eye has hypertropia
- Vertical diplopia worsens when the affected eye looks nasally
- Vertical diplopia improves with head tilt away from the affected eye
- Vertical diplopia worsens with downgaze
- CN IV is most commonly injured cranial nerve in head trauma (susceptible to shear)
Other Causes of Vertical Diplopia
- Disorders of extraocular muscles
- Myasthenia gravis
- Lesions of superior division of CN III affecting the superior rectus
- Skew Deviation (a vertical disparity in the position of the eyes of supranuclear origin)
Abducens Palsy (CN VI)
- Abducens nerve palsy produces horizontal diplopia (in milder cases, may just be incomplete “burial of the sclera” on lateral gaze)
- CN VI is particularly susceptible to injury from downward traction caused by elevated intracranial pressure; therefore, abducens palsy is important early sign of supratentorial or infratentorial tumors, pseudotumor cerebri, hydrocephalus, and other intracranial lesions
- Different from a gaze palsy, in which movements of both eyes in one direction are decreased
- CN VI lesions often affect fibers of CN VII, resulting in ipsilateral facial weakness
Other Causes of Horizontal Diplopia
- Myasthenia gravis
- Disorders of the extraocular muscles caused by thyroid disease, tumors, inflammation, or orbital trauma
The Pupils and Other Ocular Autonomic Pathways
The pupils are controlled by both parasympathetic and sympathetic pathways
Parasympathetic Pathways
(see figure 13.8 on p.541) Light enters eye —> retinal ganglion cells —> projects to both optic tracts —> (extrageniculate pathway) brachium of superior colliculus —> past LGN —> pretectal area —> Edinger-Westphal nucleus —> (preganglionic) ciliary ganglia (in the orbit) via oculomotor nerves —> (postganglionic) pupillary constrictor muscles
- A light shone in one eye causes a direct response in the same eye and a consensual response in the other eye because information crosses bilaterally at multiple levels
Accommodation Response
(another pathway for bilateral pupillary constriction) Occurs when a visual object moves from far to near, and involves:
- Pupillary constriction
- Accommodation of the lens ciliary muscle
- Convergence of the eyes
Visual signals —> visual cortex —> pretectal nuclei are activated, causing bilateral papillary constriction mediated by above described parasympathetic pathways
- This same pathway also mediates contraction of the ciliary muscle
Sympathetic Pathways
(see figure 13.10 on p. 542) Hypothalamus —> lateral brainstem/cervical spinal cord —> T1/T2 —> preganglionic sympathetic neurons in the intermediolateral cell column of the upper thoracic cord —> paravertebral sympathetic chain via white rami communicantes —> superior cervical ganglion —> carotid plexus —> pupillary dilator muscle
Pupillary Abnormalities
(see table 13.13 on p. 544) Anisocoria= pupillary asymmetry
Oculomotor Nerve Lesion
- Impaired pupillary constriction, resulting in a unilateral dilated pupil
- When lesion is complete, pupil is very large (“blown pupil”)
Horner’s Syndrome
- Triad of ptosis (upper eyelid droop), miosis (decreased pupillary size), and anhidrosis (decreased sweating of the ipsilateral face and neck)
- Caused by loss of sympathetic innervation to the pupillary dilator muscle, resulting in impaired dilation of the pupil
- Lesions at any point in above-described sympathetic pathway may produce the syndrome
Possible Locations for Lesions
- Lateral brainstem (e.g., infarct, hemorrhage)
- Spinal cord (e.g., trauma)
- First and second thoracic roots (e.g., trauma, apical lung tumor)
- Sympathetic chain (e.g., tumor or trauma)
- Carotid plexus (e.g., carotid dissection)
- Cavernous sinus (e.g., thrombosis, infection, aneurysm, neoplasm)
- Orbit (e.g., infection, neoplasm)
- Large bilateral lesions of the pons are sometimes associated with pontine pupils (both pupils small but reactive to light)
Afferent Pupillary Defect
- Marcus Gunn Pupil
- The direct response to light in affected eye is decreased/absent; consensual response of affected eye to light in opposite eye is normal
- Caused by decreased sensitivity of affected eye to light, secondary to lesions of optic nerve, retina, or eye
- Distinguish from hippus (normal brief oscillation of pupil size that may occur in response to light)
Benign (Essential, Physiological) Anisocoria
- Slight pupillary asymmetry (<.6mm) in 20% of general population; may vary from time to time
- No other associated abnormal findings
Pharmacological Miosis and Mydriasis
- Opiates —> bilateral pinpoint pupils
- Barbiturate overdose —> bilateral small pupils
- Anticholinergic agents (e.g., scopolamine, atropine) —> dilated pupils
Light-Near Dissociation
- Pupils constrict much less in response to light than to accommodation
- Argyll Robertson Pupil – associated with neurosyphilis; light-near dissociation plus small and irregular pupils
- May be seen in diabetes, Adie’s myotonic pupil, or as part of Parinaud’s syndrome
Adie’s Myotonic Pupil
- Mid-dilated pupil that reacts poorly to light
- Characterized by degeneration of the ciliary ganglion or postganglionic parasympathetic neurons
- No known cause
Midbrain Corectopia
- Lesions of midbrain may cause an unusual pupillary abnormality in which the pupil assumes an irregular, off-center shape (rare)
Ptosis
Eye Opening – uses levator palpebrae superior (CN III), Muller’s smooth muscle in upper lid (sympathetics), and frontalis muscle (CN VII) Eye Closure – uses orbicularis oculi muscle (CN VII) Ptosis – drooping of the eyelid
Potential Causes
- Horner’s syndrome
- Oculomotor nerve palsy
- Myasthenia gravis
- Redundant skin folds associated with aging (pseudoptosis)
- Nondominant parietal lobe lesion (bilateral ptosis)
- Dorsal lesions of the oculomotor nuclei affecting the central caudate nucleus (bilateral ptosis)
- Voluntary eye closure (e.g., migrainous photophobia)
Cavernous Sinus and Orbital Apex
(see figure 13.11 on p. 547)
- Region on either side of the pituitary; CN III, IV, VI, V1, and V2 all run very close to or through here
- Also, sympathetic fibers and optic nerve are nearby
- Orbital Apex – region where nearly all nerves, arteries, and veins of the orbit converge before communicating with the intracranial cavity via the optic canal and superior orbital fissure
Cavernous Sinus (CN III, IV, VI, V1) and Orbital Apex (CN II, III, IV, VI, V1) Syndromes
- Complete lesion of the cavernous sinus —> total ophthalmoplegia, accompanied by a fixed, dilated pupil
- Orbital apex lesion produces same as above, plus may involve CN II (thus visual loss)
Common Causes
- Metastatic tumors
- Direct extension of nasopharyngeal tumors
- Meningioma
- Pituitary tumors/apoplexy
- Aneurysms of the intravenous carotid
- Cavernous carotid arteriovenous fistula
- Bacterial infection causing cavernous sinus thrombosis
- Aseptic thrombosis
- Idiopathic granulomatous disease (Tolosa-Hunt syndrome)
- Fungal infections
Supranuclear Control of Eye Movements
- At least three dedicated circuits in the brainstem are responsible for: horizontal, vertical, and vergence eye movements
- Saccades – rapid eye movements that bring targets of interest into field of view. Are the only type of eye movement that can be easily performed voluntarily
- Smooth pursuit – slower eye movements, not under voluntary control, that allow stable viewing of moving objects
- Vergence – even slower eye movements that maintain fused fixation by both eyes as targets move toward or away from the viewer
- Reflex eye movements – include optokinetic nystagmus (nystagmus = rhythmic form of reflex eye movements composed of slow eye movements in one direction interrupted by fast saccadelike eye movements in the opposite direction; also called train nystagmus) and vestibulo-ocular reflex
Brainstem Circuits for Horizontal Eye Movements
- Horizontal eye movements are generated by lateral rectus (CN VI) and medial rectus (CN III) muscles
- Medial longitudinal fasciculus (MLF) interconnects CN III, IV, VI, and X nuclei
- Paramedian pontine reticular formation (PPRF) – important horizontal gaze center that provides input from the cortex and other pathways to the abducens nucleus
Brainstem Lesions Affecting Horizontal Gaze
(see figure 13.13 for effects of lesions on horizontal gaze)
Lesions
- Abducens nerve —> impaired abduction of ipsilateral eye
- Abducens nucleus —> ipsilateral lateral gaze palsy in both eyes
- PPRF —> ipsilateral lateral gaze palsy
- MLF —> internuclear ophthalmoplegia (INO) – eye ipsilateral to lesion does not fully adduct on attempted horizontal gaze, nystagmus in opposite eye; side of INO is same as side of lesion in MLF
- Common causes – MS plaques, pontine infarcts, MLF neoplasms
- MLF and adjacent abducens nucleus or PPRF —> one-and-a-half syndrome – ipsilateral INO plus ipsilateral lateral gaze palsy
Brainstem Circuits for Vertical and Vergence Eye Movements
- Vertical eye movements are generated by superior and inferior rectus and superior and inferior oblique muscles; brainstem controlling centers are located in rostral midbrain reticular formation and pretectal area
- Ventral portion mediates downgaze (especially rostral interstitial nucleus of the MLF), dorsal region mediates upgaze
Of Interest: Locked-in syndrome – large pontine lesions disrupt bilateral corticospinal tracts and abducens nuclei, eliminating body movements and horizontal eye movements. Therefore, sometimes the vertical eye movement centers in midbrain are spared, allowing communication entirely through vertical eye movements.
- Convergence – produced by medial recti
- Divergence – produced by lateral recti
Parinaud’s Syndrome
Four Components
- Impairment of vertical gaze, especially upgaze
- Large, irregular pupils with light-near dissociation
- Eyelid abnormalities
- Impaired convergence, and sometimes convergence-retraction nystagmus
Common Causes
- Pineal region tumors
- Hydrocephalus
Of Interest: Hydrocephalus in children can produce bilateral setting-sun sign, in which the eyes are deviated inward because of bilateral sixth-nerve palsies and downward because of a Parinaud’s syndrome.
Control of Eye Movements by the Forebrain
Multiple parallel pathways descend from the cerebral cortex to control eye movement circuits in the brainstem:
- Descending cortical pathways go either directly to brainstem centers for horizontal, vertical, or vergence eye movements, or via relays in the midbrain superior colliculi
- Frontal eye fields
- lie at junction between superior frontal sulcus and precentral sulcus (Brodmanns area 6, not area 8)
- overlap premotor and prefrontal cortices, reflecting roles in eye movement control and selective attention
- generate saccades in the contralateral direction via the PPRF
- Parieto-occipital-temporal cortex – responsible for smooth pursuit movements in the ipsilateral direction, via connections with the vestibular nuclei, cerebellum, and PPRF
- Cortical descending control of eye movements is heavily influenced by visual inputs arriving from primary visual cortex and visual association cortex
- Basal ganglia also modulate eye movements
Right-Way Eyes and Wrong-Way Eyes
(see figure 13.15 on p. 553)
Right-Way Eyes
- Cerebral hemisphere lesions normally impair eye movements in the contralateral direction, resulting in gaze preference toward side of the lesion
- This is normally accompanied by weakness contralateral to the cortical lesion, so the eyes look away from the side of the weakness
Wrong-Way Eyes
- Eyes look toward the side of weakness
- Possible causes: seizure activity in the cortex, large lesions such as a thalamic hemorrhage (usually accompanied by deep coma), lesions of the pontine basis and tegmentum
Cerebellar, Vestibular, and Spinal Control of Voluntary and Reflex Eye Movements
Detailed discussion of optokinetic nystagmus (OKN) and vestibulo-ocular reflex (VOR) – seems unimportant; see pp. 552-553 if you’d like this information
Notes from Clinical Cases
Symptoms Left frontal and retro-orbital headaches; history of left eye drifting to the left and diplopia with image from left eye above and to the right of image from right eye, with diplopia worse when looking to the right; left eye with limited but not absent upgaze, downgaze, and adduction, and ptosis, and a fixed dilated pupil
- Diagnosis Oculomotor nerve palsy (CN III) secondary to an aneurysm
Symptoms History of diabetes; horizontal diplopia, worse on left gaze, with incomplete abduction of the left eye
- Diagnosis Isolated abducens nerve palsy, caused by microvascular disease
Symptoms Right hypertropia and vertical diplopia worse with downward and leftward gaze and worse with rightward head tilt
- Diagnosis Isolated right trochlear nerve palsy caused by an idiopathic neuropathy of presumed microvascular origin
Symptoms On right gaze: left eye pain, limited adduction, and horizontal diplopia, with the right image vanishing when the left eye was covered; on left gaze: mild horizontal diplopia, with the left image vanishing when the left eye was covered; pain and erythema of the left orbital conjunctiva
- Diagnosis (differential: infectious, inflammatory, or neoplastic disorder) orbital myositis (orbital pseudotumor) – uncommon inflammatory condition of the extraocular muscles
Symptoms Initial left abducens palsy, evolving to ophthalmoplegia, ptosis, and a fixed dilated pupil; pain, paresthesia, and decreased sensation to pinprick in the left forehead, eyelid, bridge of nose, and upper cheek
- Diagnosis Dysfunction of CN III, IV, VI, and V1 –> left cavernous sinus syndrome; hemorrhage from a recurrent pituitary adenoma
Symptoms Left ptosis; small reactive left pupil with decreased ciliospinal reflex; decreased left facial sweating
- Diagnosis Horner’s syndrome; caused by traumatic injury or carotid dissection
Symptoms Lethargy; rightward gaze preference, with inability to move either eye past the midline toward the left; right face, arm, and leg weakness, with upgoing plantar response on the right
- Diagnosis “wrong-way eyes”; infarct in the left pons
Symptoms Left eye did not adduct past midline; right eye had sustained end gaze nystagmus on abduction
- Diagnosis Left INO localized to the left MLF caused by an MS plaque
- Then Additional sx of inability of either eye to move past midline when looking to the left; no adduction of the left eye; end gaze nystagmus on right eye abduction – left INO plus left horizontal gaze palsy = one-and-a-half syndrome (plaque enlarged to include left abducens nucleus or PPRF)
Symptoms Headaches; large pupils with minimal reaction to light but preserved reaction to accommodation (light-near dissociation); inability to look upward; lid retraction and convergence-retraction nystagmus
- Diagnosis Parinaud’s syndrome caused by pineal region tumor compressing the dorsal midbrain
Of Interest: When headaches are always on the same side, an intracranial abnormality on that side should be suspected.