This document discusses the neural control of extraocular eye movements. It covers the different types of eye movements including fixation, saccades, smooth pursuit, and vergence. It describes the relevant eye muscles, cranial nerve nuclei, brainstem structures, and cortical areas involved in generating and modulating each type of eye movement. Specific pathways and neural circuits are described for saccadic control and smooth pursuit. Clinical evaluation of saccades and smooth pursuit is also covered. Dysfunctions and lesions that can cause abnormalities in eye movements are discussed.

1. SUPRANUCLEAR CONTROL OF
EXTRAOCULAR MOVEMENTS
DR . A RGHYA D E B, D M R ES ID E NT, B IN

2. OCULAR MUSCLES- FUNCTION WISE
Agonist: the primary muscle moving the eye in a given
direction
Synergist: the muscle in the same eye (as the agonist)
that acts with the agonist to produce a given movement
Antagonist: the muscle in the same eye as the agonist
that acts in the direction opposite to that of the agonist
Yoke muscles: Two muscles (one in each eye ) that are
the prime movers of their respective eyes in a given
position of gaze.
2

3. LAWS OF EXTRAOCULAR MOVEMENTS
Hering’s law: Equal and simultaneous innervation
flows to yoke muscles concerned with the desired
direction of gaze.
Sherrington’s law: Increased innervational and
contraction of a given muscle are accompanied by a
reciprocal decrease in innervation and contraction of
its antagonist.
3

4. POSITIONS OF GAZE
Primary position: straight ahead
Secondary positions: straight up , straight down, right ,
left
Tertiary positions: up & right, up & left, down & right,
down & left
Primary deviation: the amount of misalignment when
the normal eye is fixating
Secondary deviation: the amount of misalignment when
the paretic or restrictive eye is fixating
The secondary deviation is larger than the primary
deviation
4

5. The first patient (A–C) has a complete left abducens nerve palsy with a complete left abduction defect.
The second patient (D–F) has a complete right abducens palsy with complete right abduction defects.
Although both patients have complete abduction defects with equally weak affected lateral recti, note
that in primary gaze the first patient has a smaller angle esotropia (one eye deviated inward) than the
second. The reason is that the first patient is fixing with the normal eye, and the innervation to the weak
lateral rectus remains low. The second patient is attempting to fix with the weak eye, and the
innervation to the paretic lateral rectus is increased in an attempt to move the eye to midline. Based on
Hering law, the innervation to the yoked muscle (the contralateral medial rectus) is also increased,
resulting in a large angle esotropia. This is referred to as the secondary deviation. Mistaking the
secondary for the primary deviation at a follow-up visit might lead to the false conclusion that the
patient has worsened. This is a clinical application of Hering law.

6. SUPRANUCLEAR CONTROL OF EOM
Normal eye movements are a prerequisite to vision.
The goal is to bring an object of interest onto the fovea and to
hold it steadily.
Allowable retinal drift varies with the spatial frequency of the
object being viewed 50/s for standard visual acuity charts).
Excess retinal motion degrades visual acuity and may cause
oscillopsia (illusory movement of the visual environment).
Since head perturbations are frequent during normal activities
(such as walking), compensatory mechanisms have evolved to
prevent retinal drift with head and body movements.

7. Class of eye
movement
Main function
Fixation Holds images of stationary objects upon the fovea
Vestibulo-ocular
reflex
Gaze-holding: keeps images steady on the fovea during brief head
rotations
Optokinetic
Keeps images stable on retina during prolonged sustained head
rotations
Smooth pursuit Holds images of small moving targets steady upon the fovea
Saccades Brings objects of interest onto the fovea
Vergence
Moves eyes in opposite directions to bring images of a single object
onto the fovea
Nystagmus
(quick phase)
Reset the eyes during prolonged rotation and direct gaze toward the
oncoming visual scene
FUNCTIONAL CLASSES OF EYE MOVEMENTS
Leigh JR, Zee DS. The neurology of eye movements. 3rd ed. New York: Oxford University Press, 1999:4.

8. GAZE-HOLDING
Vestibulo-ocular reflexes depend on the ability of the
labyrinthine mechanoreceptors to detect head accelerations,
while visually mediated reflexes (optokinetic and smooth
pursuit systems) rely on the brain’s ability to determine retinal
image drift.
These reflexes act as gaze-holding mechanisms that stabilize
gaze and hold images steadily on the retina.
The afferent visual system plays a critical role in gaze-holding
by providing appropriate feedback regarding desired and
actual target position and eye position.

9. GAZE-SHIFTING
Saccades are rapid conjugate eye movements that redirect
fixation so that a new object of interest falls onto the fovea.
Vergences are dysconjugate movements (ie, the eyes are
moving in opposite directions) that shift gaze between far and
near targets (convergence and divergence).
Both of these systems act as gaze-shifting mechanisms, which
aim to bring new objects of interest onto the fovea.
Normal eye movements can then be conceived in terms of a
balance between gaze-shifting and gaze-holding mechanisms,
with continuous feedback and reprogramming from the
afferent visual system.

10. ORBITAL MECHANICS AND STEP-PULSE INNERVATION
The elastic structures in the orbit support the globe and impose
a mechanical restraint on gaze control.
To overcome the viscous drag of supporting tissues, a strong
contraction of the extraocular muscles is required.
For rapid movements (e.g. saccades), a phasic increase, or burst
of neural activity in the ocular motor nuclei is required—the
pulse of innervation.
Once at its new position,, the eye must be held against the
elastic restoring forces acting to return the globe to central
position.
To hold the eye in an eccentric position, a steady contraction of
the extraocular muscles is required, arising from a new tonic
level of neural activity—the step of innervation.

11. IMPORTANCE
Without the pulse (velocity command), the progress
of the eye would be slow.
Without the step (position command), the eyes could
never be maintained in an eccentric position in the
orbit.
Moreover, the pulse and step must be correctly
matched to produce an accurate eye movement and
steady fixation following it.

12. NEURAL INTEGRATOR
Neurophysiological evidence indicates that the position
command (e.g., for saccades, the step) is generated from the
velocity command (e.g., for saccades, the pulse) by the
mathematical process of integration with respect to time.
A neural network integrates, in this mathematical sense,
velocity-coded signals into position-coded signals; this network
is referred to as the Neural Integrator.
When this process is faulty, the eye is carried to its new
position by the pulse but cannot be held there and drifts back
to the central position. This is evident clinically as gaze-evoked
nystagmus.

13. SACCADIC CONTROL
The cerebral cortex participates in the control of all classes of
eye movements.
In general, reflexive stimulus-bound eye movements originate
in posterior portions of the brain, while voluntary movements
arise from frontal areas.
The frontal cortex contains several areas responsible for the
initiation of horizontal saccades. These include-
1. Frontal eye fields (FEFs),
2. Supplementary eye fields (SEFs), and
3. Dorsolateral prefrontal cortex (DLPC).

14. FEF neurons discharge for voluntary saccades, memory-guided
saccades, and vergence movements.
The SEFs are involved in learned patterns of ocular motor
behavior.
The DLPC controls planned saccades to remembered targets.
The posterior parietal region is involved in shifting gaze toward
novel objects of interest and modulating spatial attention.
The parietal eye fields (PEFs) project to the FEFs and are
involved in exploring visual scenes & initiating reflexive visually
guided saccades.
The FEF and PEF are heavily and reciprocally interconnected.
The temporoparietooccipital (TPO) junction is engaged in
visual motion perception and smooth pursuit. It also plays a
significant role in visual fixation and gaze-holding.

15. SACCADIC PATHWAY
Hemispheric control of horizontal saccades is contralateral.
The FEF in the lateral portion of the precentral sulcus (areas 6 & 4)
receive afferent input from the PEF (involved in reflexive saccades)
and SEF (frontal lobe area involved in planning saccades).
Signals arising from the FEF (predominately non–visually guided
saccades) and the PEF (predominately visually guided saccades)
descend to the burst cells of the contralateral PPRF.
One frontal pathway projects directly to the PPRF, and another
travels through the caudate, substantia nigra, and superior colliculus
(SC) before reaching the PPRF.
The pathways through the basal ganglia maintain balance between
reflexive and purposeful voluntary saccades and help prevent
intrusive saccades.
The PEF also projects through the Superior Colliculus to the PPRF.

16. SEVERAL CELL POPULATIONS PLAY AN IMPORTANT ROLE
IN SACCADIC CONTROL
Excitatory burst neurons (within the pons & midbrain)
discharge 10 ms to 12 ms in anticipation of a saccade and
project to the motor neurons of the ipsilateral abducens
nucleus. Inhibitory neurons project to the C/L Sixth nucleus.
Omnipause neurons are distributed throughout the brainstem,
project to burst cells, and exert a tonic inhibitory effect.
They primarily act to prevent unwanted and intrusive saccades.
Omnipause neurons cease to fire approximately 15 milliseconds
before a saccade.

17. Silence of omnipause neurons allows the excitatory burst
neurons (within the [PPRF] of the pons for horizontal
movements, and within the [riMLF] of the midbrain for vertical
movements) to fire.
While inhibitory burst neurons suppress activation of the
antagonist extraocular muscles (eg, inhibition of the MR with
LR firing).
The abducens nucleus is the horizontal gaze center and
receives commands for all functional classes of eye
movements.
The motor neurons project to the I/L LR, while interneurons
send axons that cross to the C/L MLF and ascend to the C/L MR
subnucleus of the oculomotor complex.
The cerebellar vermis, fastigial nucleus, and flocculus are
involved with calibrating and modulating saccadic responses.

18. HORIZONTAL ECCENTRIC GAZE-HOLDING
Signals for eccentric gaze-holding reach the abducens nucleus
from the ipsilateral Nucleus Prepositus Hypoglossi (NPH) and
Medial Vestibular Nuclei (MVN).
These structures and their cerebellar connections serve as the
Neural Integrator for horizontal gaze-holding.
They provide the eye position signal necessary to hold the eye
steady in eccentric position in the orbit.

19. CORTICAL AND SUBCORTICAL CONTROL OF SACCADES

20. Cortical and sub-cortical pathways involved in the
generation and modulation of horizontal saccades.

21. SACCADES EVALUATION
Pathology of saccades can be divided into
1. Disorders of initiation (long latency),
2. Disorders of speed (slow saccades),
3. Absent or unwanted saccades, and
4. Disorders of accuracy (hypometric or hypermetric
saccades).

22. SACCADIC ABNORMALITIES
1. Saccadic initiation time (latency) is influenced by subject age,
attention, and level of consciousness.
B/L frontoparietal lesions may produce acquired ocular motor
apraxia, with dramatically impaired activation of volitional saccades
while involuntary saccades are normal. (eg. hemodynamic stroke)
The parietal cortex mediates saccades toward novel visual targets.
Unilateral parietal lesions may cause delayed hypometric
contralateral saccades. This is generally more prominent with right
sided (nondominant) lesions.
Basal ganglia disease can produce increased latencies for saccadic
initiation, notably in HD with lesser degrees of delay for PD.
Disorders of saccadic accuracy imply cerebellar system disease and
typically produce hypermetria (overshoot of saccades).

23. CLINICAL EVALUATION OF SACCADES
In clinic or at the bedside, voluntary saccades are assessed by
asking the patient to refixate between two targets (such as the
examiner’s fingers), usually 300 to 400 apart.
Normal refixation movements should be accomplished with
one saccade or may undershoot the target and require one or
two catch-up saccades to reach the target.
Three or more refixation saccades are considered hypometric
and abnormal, particularly if asymmetric.
Hypermetric saccades overshoot the targets and are always
abnormal, often indicating I/L cerebellar system dysfunction.
Saccadic hypometria indicates cerebral dysfunction but is
otherwise (in isolation) non-localizing.

24. ANTISACCADE TASK
The Antisaccade task requires that the patient produce an eye
movement in the direction opposite a novel visual target (eg, a
finger).
This task requires the patient to suppress the natural tendency
to refixate toward the new target and suggests damage to the
frontal lobes or the descending projections through the basal
ganglia.
This is often abnormal in Huntington chorea and other
disorders affecting frontal lobe function.

25. SLOW SACCADES
Slow saccades are always abnormal and may be caused by
several diseases, including-
1. Genetic (eg, SCA, HD, and WD),
2. Neurodegenerative (eg, PSP, advanced AD, and, rarely,
advanced ALS),
3. Infectious (eg, whipple disease and tetanus),
4. Paraneoplastic conditions,
5. PPRF lesions,
6. Ocular motor nerve,
7. Neuromuscular junction, or
8. Muscle disease.

26. SPECIFIC CONDITIONS AND LESIONS CAUSING
SACCADIC DYSFUNCTION

27. SMOOTH PURSUIT
Smooth pursuit eye movements are used to track objects
moving in the environment.
The goal of the system is to generate a smooth eye velocity that
matches the velocity of a visual target.
Visual motion processing [in temporoparietooccipital (TPO)
junction drives pursuit.
Smooth pursuit pathways are less well understood than
saccadic pathways, but a critical area, is the junction of the
occipital and temporal lobes, analogous to the medial temporal
(MT) and medial superior temporal (MST) region in monkeys.
The posterior parietal lobe and both the SEF and FEF
contribute to smooth pursuit.

28. SMOOTH PURSUIT PATHWAY
Axons descend from the I/L TPO junction and FEF to the I/L
dorsolateral pontine nucleus (DLPN).
Fibers cross and reach the C/L cerebellar flocculus and then
project to the vestibular nuclei.
The projections cross again and reach the abducens nucleus,
ipsilateral to the originating cortical signal.
Control of smooth pursuit, in distinction to saccades, is
ipsilateral: the left hemisphere is involved in leftward smooth
pursuit and vice versa.

29. Cortical and subcortical pathways
involved in smooth pursuit.
I/L
C/L
I/L
1st crossing
2nd crossing

30. SMOOTH PURSUIT DISORDERS
When the smooth pursuit system cannot keep up with target
movement, the more durable and evolutionarily older saccadic
system is called on to recapture the object of interest.
This results clinically in saccadic pursuit, in which an excessive
number of small saccades intrude on pursuit.
Symmetric loss of pursuit may be caused by a broad range of
neurologic disorders, as well as inattention, age, and
medications, and is, therefore, a nonspecific finding.
Asymmetric smooth pursuit suggests lateralized neurologic
dysfunction, usually cerebral and ipsilateral to the direction of
abnormal pursuit.
Such lesions are often located in the cortex or subcortical white
matter of lateral occipitotemporal or the dorsomedial frontal
regions

31. CAUSES OF SYMMETRICALLY IMPAIRED SMOOTH
PURSUIT
Sedative-Hypnotic Medications
Anticonvulsants
Brainstem/Cerebellar Dysfunction
Toxic-Metabolic Encephalopathies
Advanced Age
Inattention
Fatigue
Basal Ganglia Disorders
Parkinson disease
Huntington disease
Wilson disease
Progressive supranuclear palsy

32. CLINICAL EVALUATION OF SMOOTH PURSUIT
Smooth pursuit is examined clinically by having the patient
track a slowly moving accommodative target, such as the
20/200 letter on a near card.
We can normally smoothly pursue a target moving at 100 to 400
per second.
It is important to move the target at this rate; rapidly moving a
target back and forth will overcome even a normal smooth
pursuit system and give a false impression of impaired pursuit.

33. VERTICAL EYE MOVEMENT CONTROL
In contrast to horizontal gaze, which is generated by unilateral
aggregates of cerebral and pontine neurons, vertical eye
movements, with few exceptions, are under bilateral control of
the cerebral cortex and upper brainstem.
The groups of nerve cells and fibers that govern upward and
downward gaze, as well as torsional saccades, are situated in
the pretectal areas of the midbrain and involve three integrated
structures-
1. the riMLF (rostral interstitial nucleus of the MLF),
2. the INC (interstitial nucleus of Cajal)
3. the nucleus and fibers of the posterior commissure (PC)

34. Pathways for the control of vertical
eye movements

35. RI-MLF (ROSTRAL INTERSTITIAL NUCLEUS OF THE MLF)
The riMLF lies at the junction of the midbrain and thalamus, at
the rostral end of the MLF, just dorsomedial to the rostral pole
of the red nucleus.
It functions as the "Premotor" nucleus with "burst cells" for the
production of fast (saccadic) vertical versional and torsional
movements.
Input to the riMLF arises both from the PPRF and the
vestibular nuclei.
The riMLF connect to the motor neurons of the elevator, (SR,
IO) nuclei bilaterally, and the depressor (SO, IR) nuclei
ipsilaterally.
Each riMLF is connected to its counterpart by fibers that
traverse the posterior commissure.

36. INC (INTERSTITIAL NUCLEUS OF CAJAL)
The INC is a small collection of cells that lies just caudal to the
riMLF on each side.
Each nucleus projects to the motor neurons of the opposite
elevator muscles (SR and IO) by fibers that cross through the
posterior commissure, and it projects ipsilaterally and directly
to the depressor muscles (IO and SO).
The functional role of the INC appears to be in holding
eccentric vertical gaze, especially after a saccade (neural
integrator for vertical gaze)
Lesions of the INC produce a vertical gaze-evoked and
torsional nystagmus, and an ocular tilt reaction (OTR) and
probably slow in all conjugate eye movements, mainly vertical
ones.

37. PC (POSTERIOR COMISSURE)
The PC crosses posterior to the third ventricle at its junction
with the aqueduct, rostral to the SC.
The nucleus of the PC contributes to upgaze generation and
coordination between eye and eyelid movements.
A lesion here characteristically produces a paralysis of upward
gaze and of convergence, often associated with mild mydriasis,
accommodative loss, convergence nystagmus, lid retraction
(Collier sign), and, less commonly, ptosis (Parinaud syndrome).
With acute lesions of the PC, there is a tonic downward
deviation of the eyes and lid retraction ("setting-sun sign").

38. ROLE OF MLF
The MLF is the main conduit of signals that control vertical gaze
from the vestibular nuclei in the medulla to the midbrain
centers.
For this reason, with INO, along with the characteristic
adductor paresis on the affected side, vertical pursuit and the
VOR are impaired.
This is most evident when there are bilateral internuclear
ophthalmoplegias.
Vertical deviation of the ipsilateral eye (skew) may also be seen
in cases of unilateral internuclear ophthalmoplegia.

39. VERGENCE
The vergence system serves to keep both foveas on a target
that is changing distance from the observer (eg, convergence
when fixating a target approaching the nose).
Dysfunction of the vergence system results in horizontal ocular
misalignment at a particular distance, producing binocular
horizontal diplopia at distance or near viewing.
Supranuclear circuitry is also responsible for fusion of any
phorias.
Most healthy patients have small horizontal phorias (esophoria
or exophoria); however, these are asymptomatic due to proper
functioning of the vergence networks, which serve to fuse small
amounts of misalignment.

40. VERGENCE-RELATED HORIZONTAL DIPLOPIA VERSUS THE
HORIZONTAL DIPLOPIA RELATED TO SIXTH NERVE PALSY
A sixth nerve palsy will demonstrate incomitant measurements
(impaired abduction of one eye produces an esotropia that
increases in gaze toward the paretic side), while vergence
dysfunction creates a comitant (the same in all positions of
gaze) misalignment for a given viewing distance.
Occasionally dysfunction of these pathways from medications,
structural origin, fatigue, or idiopathic causes produces
intermittent binocular horizontal diplopia because of
manifestation of a baseline horizontal phoria.
Convergence insufficiency is perhaps the most common of the
vergence dysfunction patterns, producing a larger exophoria at
near than distance and horizontal diplopia at near.

41. VESTIBULAR-OCULAR SYSTEM
The vestibulo-ocular reflex (VOR) produces conjugate eye
movements that are equal and opposite to head movements.
Components: (1) the horizontal VOR & (2) the vertical &
torsional VOR.
The VOR depends on direct connections between the peripheral
vestibular system (ie, labyrinth and vestibular nerve) and the
central ocular motor system (ie, the ocular motor nuclei).
The cerebral modulation of the VOR remains poorly understood,
Recent evidence suggests that cortical processing of vestibular
input is distributed among multiple areas, including the
posterior insular cortex and the parietal and frontal cortex

42. HORIZONTAL VOR
The horizontal VOR is produced by projections from the
horizontal semicircular canals (SC) to the I/L oculomotor
nucleus and C/L abducens nucleus, causing the yoked medial
and lateral recti muscles to fire.
These fibers carry the head and eye velocity commands.
The integrated position command is generated by the nucleus
prepositus hypoglossi and the medial vestibular nucleus, and
then carried to the medial and lateral rectus motor neurons.

43. The excitatory connections
of the horizontal VOR:
Leftward head rotation
causes endolymph flow in
the horizontal semicircular
canals to excite hair cells,
which transmit eye velocity
commands to the ipsilateral
vestibular nucleus (not
shown), then to the
contralateral abducens
nucleus.
MLF

44. VERTICAL AND TORSIONAL VOR
The vertical and torsional VOR are generated by projections from the
anterior and posterior semicircular canals to the oblique and vertical
rectus muscles.
Activation of B/L anterior canals by downward head acceleration
induces the upward VOR, while activation of B/L posterior canals by
upward head acceleration induces the downward VOR.
Contraction of the I/L SR and C/L IO, in response to activation of the
I/L anterior canal, results in elevation and C/L torsion of both eyes.
Contraction of the I/L SO and C/L IR, in response to activation of the
posterior canal, results in depression and C/L torsion of both eyes.
When vertical head acceleration activates both anterior canals, the
torsional signals cancel out, resulting in purely vertical movement.
Similarly, when head roll or tilt activates both vertical posterior
canals, the vertical signals cancel each other, producing a purely
torsional movement.

45. ORIENTATION OF SEMICIRCULAR CANALS

46. The vertical vestibulo-ocular reflex is generated by endolymph movement
in the anterior and posterior semicircular canals (SCCs).
Downward head rotation (top) activates both anterior SCCs and induces
(via connections to the elevation subnuclei of the oculomotor nerve)
upward slow eye movements.
Upward head rotation (bottom) stimulates both posterior SCCs and causes
(via connections with the depressor subnuclei of the oculomotor nerve
and the trochlear nuclei) downward eye movements.

47. VOR CANCELLATION
Adequate cancellation of the VOR is also necessary when
pursuing an object that moves in synchrony with head and eye
movement.
Without appropriate cancellation, the VOR moves the eyes in
the direction opposite to the head, then requiring a catch-up
saccade to reach the target.
Impaired cancellation of the VOR, often associated clinically
with impaired smooth pursuit, is a sensitive but relatively
nonspecific localizing sign of cerebral, brainstem, or, most
often, cerebellar disease.

48. CLINICAL EVALUATION OF THE VOR
VOR gain (the ratio of eye velocity to head velocity as the eyes and
head move in opposite directions) must be close to 1.0 to maintain
normal vision and can be assessed in clinic.
Abnormal VOR gain (too low or too high) causes images to move
across the retina and results in visual blur or apparent motion of the
environment (oscillopsia).
The dynamic visual acuity test is an easy method to detect B/L VOR
gain abnormalities; the patient’s head is rotated left and right at 2 Hz
to 3 Hz while attempting to read the Snellen visual acuity chart.
If VOR gain is normal, visual acuity should be the same as their best
corrected visual acuity performed with the head stationary.
If Snellen visual acuity falls by two or more lines, VOR gain is too low
or too high.

49. HEAD IMPULSE TEST (HIT)
The head impulse test is a more sensitive technique, able to detect
unilateral or bilateral abnormalities of VOR gain.
For this test, the patients are asked to fixate on a distant target
wearing their usual and appropriate correction.
The examiner grasps the patient’s head and rapidly rotates the head
horizontally, about 200 to 300.
The VOR response elicited results from excitation of the ipsilateral
horizontal semicircular canal.
If VOR gain is normal, the patient’s gaze remains steadily upon the
target.
A catch-up saccade back to the target at the end of the head rotation
suggests abnormal VOR gain on the side of the head thrust.

50. VESTIBULAR NYSTAGMUS
Imbalance of the VOR induces nystagmus.
The slow phase of peripheral vestibular nystagmus is enhanced
by removal of fixation, using either Frenzel (+20 diopter) lenses
or by performing ophthalmoscopy on one eye while covering
the other.
Central vestibular nystagmus is not influenced by fixation.

51. CEREBELLAR CONTROL OF EYE MOVEMENTS
The cerebellum plays a major role in coordinating and
calibrating all eye movements.
The vestibulocerebellum (flocculus, paraflocculus, nodulus,
and ventral uvula) deals with stabilization of sight during
motion.
The dorsal vermis and fastigial nuclei influence voluntary gaze
shifting.

52. FLOCCULUS AND PARAFLOCCULUS
The floccular complex helps generate smooth pursuit and
governs the neural integrator in maintaining eccentric gaze.
Damage to the floccular complex results in saccadic pursuit
and impaired gaze-holding, manifesting as gaze-evoked
nystagmus and rebound nystagmus.
This complex also calibrates the pulse–step ratio of saccades
and the amplitude of the VOR, adjusting them in response to
changes in the visual environment and visual needs.

53. DORAL VERMIS AND FASTIGIAL NUCLEI
The dorsal vermis and fastigial nuclei play critical roles in
saccadic control and have roles in the coordination of smooth
pursuit.
The fastigial nucleus accelerates C/L saccades through
projections looping around the superior cerebellar peduncle
and terminating at the C/L PPRF.
Lesions of the fastigial nucleus (or projections) cause
hypometric C/L saccades and hypermetric I/L saccades.
Since the fastigial nucleus is under inhibitory control of the
vermis, lesions of the latter structure result in hypometric I/L
and hypermetric C/L saccades.
Vermal lesions also impair smooth pursuit, usually toward the
side of the lesion.

54. CEREBELLAR CONTROL OF EYE MOVEMENTS

55. HORIZONTAL GAZE DISORDERS

56. ABDUCENS NUCLEUS LESION
There is an inability to activate the I/L LR and C/L MR for all
classes of eye movements, including VOR.
Nuclear abducens palsies are often accompanied by an
ipsilateral peripheral facial nerve palsy (due to the proximity of
the facial colliculus).
The gaze palsy may be asymmetric with the abducting eye
more prominently affected.
This may be due to selective vulnerability of the motor neurons
compared to interneurons or may reflect concomitant
involvement of the abducens fascicle.
The etiology is usually either ischemia or compression/
infiltration.

57. PARAMEDIAN PONTINE RETICULAR FORMATION
(PPRF) LESION
Lesions of the PPRF cause selective loss of ipsilateral
horizontal saccades.
Acutely, there may be a contralateral gaze deviation (eg, a right
gaze deviation with a left PPRF lesion).
In contrast to lesions involving the abducens nucleus, the
horizontal oculocephalic reflex (doll’s eye) in a PPRF lesion is
preserved, since vestibular fibers project directly to the
abducens nucleus.
Etiologies are similar to abducens nerve palsy

58. CEREBRAL GAZE PALSY
Acute, unilateral hemispheric injury may cause transient gaze
palsy or gaze deviation.
This most often occurs with fronto-parietal and right-sided
lesions.
The eyes are deviated ipsilateral to the lesion.
The gaze deviation may be overcome with horizontal
oculocephalics and usually changes within days to a gaze
preference, in which the patient can redirect gaze with
prompting.
This should be distinguished from gaze apraxia, which implies
difficulty initiating visually guided saccades.
The most common causes are stroke and tumor.

59. DISORDERS OF GAZE ASSOCIATED WITH HEMISPHERIC
AND BRAINSTEM LESIONS.
(A) Destructive lesion in the frontal lobe of the right cerebral hemisphere.
(B) Seizure arising from the frontal lobe of the right cerebral hemisphere.
(C) Destructive lesion in the right pons.

60. INTERNUCLEAR OPHTHALMOPLEGIA (INO)
Lesions of the MLF may result in impaired adduction during
conjugate gaze contralateral to the lesion: an INO.
The MLF lesion is on the side of the poor adduction.
Dissociated nystagmus of the abducting eye is a common,
although not invariant, feature and most likely reflects central
adaptation.
Subtle INO may manifest as a slowing of adducting saccades
(“Adduction lag”) compared with abducting movements.
An INO can be differentiated from a partial third nerve palsy by
the lack of other signs of third nerve dysfunction and the
preservation, in some cases, of medial rectus function during
convergence.

61. ADDUCTION LAG IN INO
A 27-year-old woman developed horizontal diplopia and oscillopsia.
Examination revealed bilateral INO, greater on left gaze.
(A) Primary position (0.0s);
(B) adduction lag of the right eye on a rapid left saccade (0.10s);
(C) near-complete adduction of the right eye at the end of the saccade (0.20s).

62. The misalignment produced by INO may cause visual blurring,
diplopia, loss of stereopsis, and asthenopia (eye fatigue).
Bilateral INO may cause a large exotropia (eyes turned out)
known as wall-eyed bilateral INO (WEBINO), and patients note
horizontal diplopia in all directions of gaze.
The etiology of INO varies with the age of the patient.
In children, the M/C cause is neoplasm => demyelination.
This is reversed in adults, in whom demyelination
predominates.
In older adults, ischemia is the most frequent etiology because
the MLF is supplied by end arteries (perforating vessels from
the basilar), and the INO is typically unilateral.

63. BILATERAL INO
A 47-year-old woman presented with horizontal diplopia. Examination
revealed large-angle exotropia and bilateral INO. (A) Limited adduction of
the left eye on right gaze. (B) Limited adduction of the right eye on left gaze.
(C) Spared convergence of the eyes.

64. INO WITH SKEW DEVIATION
A 30-year-old woman with MS developed horizontal, vertical, and
torsional diplopia. Examination revealed right INO (with incomitant
exotropia greatest in left gaze) and skew deviation (with comitant right
hypertropia in all directions of gaze). A demyelinating lesion of the right
MLF accounts for this pattern of misalignment.

65. ONE-AND-A-HALF SYNDROME
Lesions of the ipsilateral abducens nucleus and ipsilateral MLF
cause loss of all horizontal eye movements except for
abduction of the contralateral eye.
Vertical and vestibular movements are spared, and a skew
deviation is common.
Acutely, the contralateral eye may deviate outward due to
unopposed resting neural activity reaching lateral rectus muscle
from the intact abducens nucleus, a syndrome called paralytic
pontine exotropia.
Etiologies include ischemia, demyelination, and tumor.

66. LEFT ONE-AND-A-HALF SYNDROME
Left one-and-a-half syndrome due to pontine
tegmental lesion involving the left abducens
nucleus (or left PPRF projecting to the
abducens nucleus) and MLF originating from
the right abducens nucleus, sparing the latter.
Because the left abducens nucleus gives rise to the left MLF projecting
contralaterally, the lesion essentially involves MLF bilaterally and
abducens nucleus ipsilaterally.
A, Exotropia of the right eye at primary gaze.
B, Apparent left internuclear ophthalmoplegia on rightward gaze.
C, Complete saccadic palsy on attempted leftward gaze.

67. THALAMIC ESOTROPIA AND WRONG-WAY DEVIATION
Thalamic lesions (usually hemorrhagic) may cause horizontal
gaze abnormalities.
Acute thalamic hemorrhage may be associated with a
contralateral gaze deviation (ie, right thalamic lesion causing
left gaze deviation).
This has been called a wrong-way deviation, since it is opposite
what would be seen in a cerebral lesion.
The etiology is unclear but may be related to an irritative focus
causing inappropriate stimulation.
Thalamic esotropia (also called pseudoabducens palsy) is an
esodeviation (eyes turned in) that may be seen with acute
thalamic lesions.
The mechanism may be disinhibition of medial rectus
subnucleus neurons that function in convergence.

68. VERTICAL GAZE DISORDERS
Patients with acute or subacute pareses of vertical gaze usually
have lesions located within the midbrain.
Since vertical gaze shifts are initiated bilaterally, unilateral
hemispheric and brainstem lesions cause only minor vertical
eye movement abnormalities.
Lesions at different levels of the midbrain may produce distinct
ocular motor deficits.

69. PARINAUD SYNDROME (DORSAL MIDBRAIN
SYNDROME)
It results from damage to the Posterior Commisure.
Characteristic features include limitation of upward eye
movements, tonic sustained downgaze (setting sun sign), and
mid-dilated pupils displaying light-near dissociation (due to
involvement of the pretectal nuclei).
Additional signs include eyelid retraction in primary gaze
(Collier sign) and convergence-retraction nystagmus with
attempted upgaze.
The nystagmus is best elicited by having the patient attempt
upward saccades (or by having the patient watch a
downwardly moving optokinetic nystagmus tape) and appears
as a series of repetitive convergence movements associated
with globe retraction.

70. PARINAUD SYNDROME
A, Impaired supraduction (top panel) greater than infraduction (bottom panel) is
present. Note eyelid retraction in bottom panel.
B, Light-near dissociation with impaired light reaction in both eyes, but retained near-
induced miosis (sans tonic pupil response).

71. The most common causes of Parinaud syndrome are pineal
area tumors, midbrain infarction, hydrocephalus (due to
dilation of the third ventricle and pressure on the dorsal
midbrain).
Limitation of upward gaze with no other features of Parinaud
syndrome is often encountered in older adults; this is believed
to represent a consequence of aging, with no lesion detectable.

72. BELL’S PHENOMENON
Bell phenomenon refers to the upward and often outward
ocular deviation with attempted eyelid closure against
resistance.
When upward eye movements are impaired, the presence of
an intact Bell phenomenon, usually associated with intact
vertical VOR, indicates a supranuclear etiology.
GRADING
Good=>2/3 of cornea disappears
Fair= 1/3 – 2/3 of cornea disappears
Poor= <1/3 of cornea disappears
VARIANT
Inverse- upward & inward
Reverse- downward & outward
Preverse- different directions

73. SKEW DEVIATION
As mentioned earlier, it is possible for skew deviation to
accompany INO because the MLF contains vestibular pathways
maintaining vertical eye position in addition to interneurons
from the abducens nucleus to the MR subnucleus.
In cases where there is selective damage of the vestibular
pathways, however, skew deviation will occur in the absence of
INO.
Imbalance of vestibular inputs leads to a cyclovertical
misalignment of the eyes, typically with a comitant vertical
deviation that does not follow a pattern characteristic of third
or fourth nerve palsy.

74. FOURTH NERVE PALSY VS. SKEW DEVIATION
Although the pattern of misalignment may resemble a fourth
cranial nerve palsy, the direction of torsion helps differentiate
between the two disorders.
With a skew deviation, the higher eye is incyclotorted, while in
fourth cranial nerve palsy, the higher eye is excyclotorted.
This may be determined either by using a Maddox rod or
observing the fundus with a direct ophthalmoscope and noting
the direction of torsion.
The hypertropia and excyclotorsion in skew deviation are
often minimized or absent when the patient is in the supine
position compared to an upright position.

75. OCULAR TILT REACTION (OTR)
A 53Y/F presents with a c/o double vision.
It was acute in onset, painless, and first noticed two
weeks prior, immediately upon awakening from a
cerebral angiogram with PCA aneurysm stenting and
coiling.
She complains of binocular diplopia that is vertical in
nature.
It is relieved with closing of either eye.
The diplopia is unchanged in any particular gaze direction
or head positioning and is similar for both distance and
near.

76. DW-MRI BRAIN
Hyperintensity (diffusion restriction) in the cerebellum,
right occipital lobe, and right paramedian midbrain.

77. OCULAR EXAM
Visual Acuity: Right eye (OD): 20/25; Left eye (OS): 20/25
Pupils: Both eyes (OU): 3 mm in dark, 2 mm in light, no RAPD
Motility: Full OU
Alignment :
• Alternate head position: right head tilt
• A 7-8 prism diopter comitant left hypertropia
• 5 degrees of excyclotorsion OD and 7 degrees of
incyclotorsion OS on double Maddox rod testing

78. Figure 2: The patient had a very small angle, comitant left
hypertropia (LHT). She adopted a compensatory right head tilt
(not shown) and there was 5 degrees of excyclotorsion OD and 7
degrees of incyclotorsion OS.

79. FIGURE 3: EXCYCLOTORSION OD AND
INCYCLOTORSION OS

80. DIAGNOSIS
Right ocular tilt reaction – skew deviation,
fundus torsion, and torticollis, secondary to
posterior circulation infarction.

81. PATHOPHYSIOLOGY
The vestibular system plays a major role in control of
head-eye posture in the roll plane – the plane in which
the head or body tilt or rotate from side to side.
Under normal physiologic conditions, a change in head or
body position in the roll plane initiates asymmetric
sensory input from the vertical semicircular canals and
utricle to the central vestibular system as a response.
For example, consider a leftward body tilt in the roll
plane.
Physiologically, this would initiate a compensatory
rightward ocular tilt reaction.

82. Figure 4: Left: A physiologic ocular tilt reaction (OTR) in response to a left body tilt
in the roll plane – there is a compensatory right head tilt with downward rotation
and excyclotorsion of the right eye and upward rotation and incyclotorsion of the
left eye.
Right: A pathologic OTR will have the same changes in head posture, eye position
and rotation as the physiologic OTR in the absence of a change in body position in
the roll plane to stimulate it.

83. If the body is tilted to the left, it causes the left eye to be
lower in space than the right.
The compensatory skew deviation will cause subsequent
upward rotation of the lowermost left eye and downward
rotation of the uppermost right eye to realign them.
Also, when the body is tilted to the left, there is a torsional
deviation of both eyes toward the left.
The compensatory ocular counter-roll results in incyclotorsion
of the lt eye and excyclotorsion of the rt eye relative to the
head, so that there is no torsion of the eyes relative to space.
The third component of the physiologic OTR is the
compensatory head tilt or torticollis that will more closely
realign the head with the gravitational vertical. In the example
of a leftward body tilt in the roll plane, this will result in a
compensatory rightward head tilt.

84. PATHOLOGIC OTR
In a pathologic OTR, a unilateral lesion (or stimulation) of
the utricle or its pathways will result in asymmetric
vestibular input to the CNS that mimics a change in body
position in the roll plane as sensed by the CNS.
This will result in an OTR in the absence of any true body
tilt in the roll plane –
• this can be tonic or paroxysmal and
• can be a complete or partial with only certain components
becoming manifest (i.e., only a skew deviation or only
synkinetic ocular torsion).

85. FIGURE 5: : ANATOMY & LOCALIZATION
Note that the
schematic on the left
is showing a right
OTR resulting from
an ipsilateral lesion
of the pathway if it is
caudal to the
decussation in the
pons or contralateral
if it is rostral to this
decussation.

86. PRESENTATION
Pts do not always present with the entire spectrum of the OTR
(i.e., skew deviation, ocular torsion, and torticollis), but can
present with variable components and severity of each.
An isolated skew deviation typically presents as a fairly
comitant, acquired, vertical misalignment of the eyes with a
full range of extraocular movements.
There is usually some degree of incyclotorsion of the
hypertropic eye or excyclotorsion of the hypotropic eye (or
both), which help differentiate it from CN IV palsy.
These patients typically report vertical diplopia.
There are variations of skew deviation including comitant,
incomitant, paroxysmal, periodic alternating, lateral
alternating, and transient neonatal.

87. RULES OF OTR
The direction of torsion of the eyes will be the same as the
direction of the ocular tilt reaction (i.e., in a right ocular
tilt reaction there will be incyclotorsion of the left eye,
excyclotorsion of the right eye, or both – torsion of the
eyes to the right).
This is also true of the head tilt (i.e., a right ocular tilt
reaction will have a right head tilt).
The hypotropic eye in the skew deviation will correspond
to the side of the ocular tilt reaction (i.e., a hypotropic
right eye will be present in a right ocular tilt reaction with
a corresponding skew deviation).

88. SUPRANUCLEAR MOTILITY DISORDERS
IN SPECIFIC DISEASES

89. PARKINSON DISEASE
convergence insufficiency (CI):
• Historically, binocular horizontal diplopia at near, visual blurring
at near after reading for a set time period (usually 5 to 10
minutes), and relief of symptoms with monocular occlusion.
• O/E- reduced convergence amplitudes, remote near point of
convergence, and exodeviation at near.
Prolonged saccadic latency, hypometric saccades, & impaired smooth
pursuit.
Vertical saccadic initiation may be more impaired than horizontal.
Saccadic velocity is unaffected or only minimally affected.
Smooth pursuit gain is decreased, and catch-up saccades are
frequently observed.
Increased saccadic intrusions (usually square-wave jerks) are seen in
up to 18% of patients with PD

90. PROGRESSIVE SUPRANUCLEAR PALSY
At first, slowing of voluntary saccades, f/b hypometria, which
initially involves vertical gaze, downgaze before upgaze, and is
the main signature of the disease
In the early stages of PSP, the gaze palsy is truly supranuclear;
full excursions of the eyes in all directions can be obtained
with the oculocephalic (doll’s head) maneuver.
With time, however, there is loss of the oculocephalic reflexes
and Bell’s phenomenon, owing to degeneration of the ocular
motor nerve nuclei.
Excessive number of square-wave jerks (>10/min) during
fixation is also seen.

91. Formal oculomotor recordings of PSP patients have found
impaired saccadic velocity and reduced gain of reflexive
saccades, impaired inhibition in the antisaccade task, with
poor self-correction of antisaccade errors.
This provides evidence for prefrontal lobe dysfunction
The VOR gain is reduced in patients with PSP compared with
patients with IPD and MSA, and cancellation of the VOR is also
impaired.
Convergence eye movements are also commonly impaired.
Smooth pursuit eye movements are abnormal due both to the
intrusion of square-wave jerks and to a reduced pursuit gain.
Optokinetic, rotational, and caloric stimuli typically produce a
tonic drift of the eyes in the direction of the slow phase.

92. (A) Patient looking straight at the camera. Note the characteristic wide-
eyed stare (asymmetrical here) with furrowing of the forehead.
(B) Attempted downgaze (note descent of the eyebrows).
(C) Full downward gaze, elicited with the vestibulo-ocular reflex.

93. FACIAL APPEARANCE AND SUPRANUCLEAR GAZE PALSY
IN PSP.
(D) Attempted upgaze. (E) Much greater upgaze is achieved with the
vestibuloocular reflex.
(F, G) Voluntary horizontal eye movements are relatively less affected,
but still slightly limited.

94. REFERENCES
Gregory P. Van Stavern. Supranuclear motility. Continuum
Lifelong Learning Neurol 2009;15(4):128–149.
Adams and Victor's Principles of Neurology. Tenth edition.
McGraw-Hill education, 2014
Leigh JR, Zee DS. The neurology of eye movements. 3rd ed.
New York: Oxford University Press, 1999:4.
Kirkpatrick CA, Thurtell MJ. Ocular Tilt Reaction: 53-year-old
female complaining of vertical diplopia following a stroke and
found to have a skew deviation, fundus torsion, and torticollis.
Dec 31, 2014

95. THANK YOU