Medical Neuroscience: Eye movement Clinical Correlation

March 15, 2004

Joel I. Shenker, M.D., Ph.D.
Department of Neurology
924-5548
jis2p@virginia.edu
Joels Rules/Advice:
1. Neurologist always start with: levelize, lateralize, localize
2. In medical school (and beyond) you really do need to know:
a. the three cranial nerves that move the eyeball, the muscles they supply, and what
each muscle does
b. the extra functions of cranial nerve 3
c. the medial longitudinal fasciculus (MLF) syndrome (aka internuclear
ophthalmoplegia, [INO]) gets asked about a lot.
3. Lesions above the brainstem produce abnormal eye movements that remain conjugate.
4. If the two eyes do not stay conjugate, if there is a brain lesion it is at or between cranial
nerves 3, 4, 6.
5. Lesions of cranial nerve 3, 4, 6 weaken muscles (i.e. no matter how you test it, the muscle
is always weak; this is a lower motor neuron [LMN] injury).
6. Lesions between cranial nerves 3, 4, 6 impair movements (i.e. depending on how you test
it, the movement may or may not fail; if supranuclear, this is an upper motor neuron
[UMN] injury).
7. To determine weakness, make the muscle do what it is supposed to do (sounds simple,
somehow easily forgotten)
8. Not everything is known, and not everything makes sense (to us).
Highlights you should know (at least some day) from reading, study, or class discussion:
1. Some eye movements
a. The eye is a globe that (like the earth) can rotate around an axis. The eyeball has
three kinds of movements, each created by twisting around one of three axes:
i. Horizontal movements are created by a pole that pokes through the eye from
top to bottom
1. abduction: the eyeball rotates to point the pupil outward
2. adduction: the eyeball rotates to point the pupil inward
ii. Vertical movements are created by a pole that pokes through the eye from left
to right
1. elevation: the eyeball rotates to point the pupil upward
2. depression: the eyeball rotates to point the pupil downward
iii. Torsion movements are created by a pole that pokes through the eye from
front to back
1. intorsion: the eyeball rotates so that that the top of the orbit rotates
toward the nose (the bottom of the eyeball rotates away from it)
2. extorsion: the eyeball rotates so that that the top of the orbit tilts away
from the nose (the bottom of the eyeball rotates toward it)

2. Eye movement control depends on coordination at several levels of the nervous system.
a. Peripherally, there are 6 muscles that move the eyeball
Muscle
Lateral rectus
(LR)
Superior rectus
(SR)
Inferior rectus
(IR)
Superior oblique
(SO)
Inferior oblique
(IO)
Medial rectus
(MR)

Main action
Abduction

Lesser action(s) CN Comment

6 Only thing CN6 does

Elevation
(when eye is abducted)
Depression
(when eye is abducted)
Depression
(when eye is adducted)
Elevation
(when eye is adducted)
Adduction

Adduction
Intorsion
Adduction
Extorsion
Adduction
Intorsion
Adduction
Extorsion

b. Centrally, the main role players are

i. frontal, parietal, and occipital
cortex
1. EG: area 8 (frontal eye
field) in posterior
frontal lobe drives both
eyes horizontally to
gaze in the contralateral
direction
ii. cranial nerves 3, 4, and 6 nuclei
and nerve
iii. fiber pathways between these
1. supranuclear cortical
fibers descending to
innervate the nuclei
2. medial longitudinal
fasciculus (MLF)
allows CN 6 to
coordinate with the
contralateral CN3

3
3
4
3
3

Only thing CN4 does;

Oblique = weird
Oblique = weird

3. There are different types of eye movements to control

a. Saccades: voluntarily move eyes from one point, quickly to another
b. Smooth pursuit: Follow a moving object
c. Vergence: Point both eyes inward to look at something near
d. Vestibulo-ocular movements: Reflexive movements to adjust for head movement
e. Fixation: Keep eyes on a stationary target.
4. Eye movement findings (clinically)
a. dysconjugate movements: One eye is looking at a different place than the other
b. nystagmus: rapid, rhythmic jerking of eyeball
c. neighborhood findings
i. ptosis: droop of upper eyelid
ii. anisocoria: unequal pupil diameters
iii. midriasis: pupil is too big
iv. miosis: pupil is too small
Below are some cases written by Dr. Thomas P. Bleck. Use these for practice, and to be able to
apply material learned in your reading and in class. From a clinicians point of view, these
cases are all fairly classic and would not be unusual for you to see in the real life of patient care.

Case I
A 43 year old man is found sprawled on the ground in a public park. He is breathing 12 times
per minute and has a pulse of 110 beats per minute. He does not speak or follow commands to
move his face, arms, or legs. He wears a medic alert bracelet indicating a history of hypertension
and diabetes mellitus. His eyes are closed, but when they are held open he is noted to have
spontaneous conjugate horizontal movements of the eyes from side to side.
Questions:
1. What anatomic systems are responsible for horizontal conjugate gaze in unconscious
patients?
In horizontal gaze, the eyes must move in close synchrony. The problem is that horizontal
eye movements must coordinate a cranial nerve III muscle (medial rectus) with a cranial
nerve VI one (lateral rectus). So, there must be a way to keep the IIIrd and IVth nuclei
integrated, even though they are in very different areas of the upper brainstem. This
system starts in the parapontine reticular formation (PPRF), a collection of neurons near
the abducens (VI) nucleus (some consider it a part of that nucleus). The PPRF receives
inputs mainly from the contralateral frontal eye field (FEF), located in the posterior lateral
frontal cortex. PPRF neurons direct the ipsilateral abducens nucleus (VI) to contract the
lateral rectus muscle. This abducts the eye ispilateral to the PPRF. At the same time,
axons that cross over to ascend rostrally in the contralateral medial longitudinal fasciculus
(MFL) direct the oculomotor nucleus (III) contralateral to the PPRF to contract the medial
rectus muscle. This adducts the eye contralateral to the PPRF. Thus, the left PPRF moves
both eyes left, and the right PPRF moves both eyes right.
2. What does the presence of the spontaneous eye movements tell you about the cause of this
patients unresponsive state?

Impaired level of consciousness requires brain dysfunction somewhere, and there are only
a few places where that can be: the reticular activating system, which courses through the
brainstem and may poke up into the thalamus, or the bilateral hemispheric cortex. So, if a
patient has impaired level of consciousness, there must be dysfunction in the brainstem,
bilateral thalamus, or diffuse bilateral cerebral hemispheric cortex. Since horizontal eye
movements in this patient remained conjugate, then cranial nerves III and VI were intact
as were the PPRF and MLF. So, a good chunk of the brainstem was healthy. The cause of
this patients unresponsiveness, then, was dysfunction at the very high brainstem, bilateral
thalamus, or bilateral cerebral hemispheric cortex. Most likely, it was cortical dysfunction,
given the extra vulnerability cortical neurons have to hypoglycemia.
The rescue squad personnel determine that the patients blood glucose is 35 mg/dL, and
administer 25 grams of glucose. The patient awakes abruptly, and the spontaneous horizontal
eye movements are replaced by normal volitional eye movements.
Questions:
1. What cerebral cortical structures are now in command of brainstem eye movement centers?
The FEFs (see above).
2. What different functions do these cortical eye movement centers subserve?
Each FEF directs the contralateral PPRF to make the eyes move horizontally, to look away
from the FEF in question.
3. Why did the glucose cause the patient to awaken?
The patient had hypoglycemia. Since brain cells are so dependent on glucose from the
blood (they do not have glycogen stores of their own), hypoglycemia causes brain cells to
work poorly. Some brain cells are more vulnerable to this than others. In general, cortical
cells are more vulnerable than those in the brainstem (think about why thats a good way
for the system to work). Giving glucose restored the patient to normo-glycemia and
restored normal cerebral function.
The patient is transported to the hospital. While waiting in the emergency department, he is
found to be confused. When he attempts to look in either horizontal direction, the abducting eye
fails to abduct completely, and he reports diplopia. He is given 100 mg thiamine, and within two
hours both his mental status and his eye movements are normal.
Questions:
1. What happened?
The patient had eye movement abnormalities and delirium after a glucose bolus, resolving
with thiamine. This pattern suggests Wernickes encephalopathy. This condition occurs in
people who are thiamine depleted, often from poor nutrition (e.g. alcoholics, elderly people
with poor appetite). Thiamine is necessary for mitochondrial mediated aerobic metabolism
of glucose. Without it, nerve cells resort to anaerobic metabolism of glucose, and this can
be toxic to nerve cells. Some cells are more vulnerable to this toxicity than others.
Brainstem nuclei that control eye movements are especially affected acutely, and neurons
in the midline of the diencephalon can die off chronically (especially the mammillary bodies

and mediodorsal nucleus of the thalamus). So, in general, if someone may have a thiamine
deficiency, do not give him/her glucose first, because that would worsen the problem! Give
thiamine first, and then glucose is OK. If patients survive Wernickes encephalopathy
(mortality rate is high), if they had suffered permanent diencephalic damage they may go
on to have a permanent memory disorder called Korsakoffs amnesia. These individuals
have anterograde amnesia (i.e. they cannot form new memories well) and, most
characteristically, they tend to confabulate (make up) memories to fill in the gaps.
2. What else could have gone wrong had he not received thiamine?
See above.

Case II
A 43 year old man is found sprawled on the ground in a public park. He is breathing 12 times
per minute and has a pulse of 110 beats per minute. He does not speak or follow commands to
move his face, arms, or legs. He does not move his eyes horizontally, but can open his eyes
spontaneously or on command. He can move his eyes vertically but not horizontally. He is able
to answer yes/no questions by blinking his eyes. He wears a medic alert bracelet indicating a
history of hypertension and diabetes mellitus.
Questions:
1. What anatomic systems are responsible for vertical eye movements?
(Compare this to the explanation of horizontal movements.) Vertical movements are
coordinated in the brainstem at the level of the midbrain. The areas of cortex that drive
this brainstem center are less clear than in horizontal eye movements, but probably involve
both frontal and occipital cortex. Anyway, all the vertical eye movements are controlled by
either IIIrd or IVth nerve functions, so there is no need for a longitudinally long fiber system
(as there was with the MLF and horizontal movements). Thus, this system is less
vulnerable to damage. It can be impaired in certain neurological disorders, though (e.g.
progressive supranuclear palsy [PSP]). Upgaze depends more on dorsal midbrain (e.g. in
Parinauds syndrome, a mass such as a pineal gland tumor compresses this area and
impairs upgaze). Downgaze depends more on a midbrain system that is a bit more ventral,
but still dorsomedial to the red nucleus (rarely, strokes can selectively lesion it). The basic
idea is that these midbrain centers have bilateral outputs to the IIIrd and IVth cranial nerve
nuclei so as to coordinate movements, as indicated, of the elevator (i.e. superior rectus,
inferior oblique) or depressor (i.e. inferior rectus, superior oblique) muscles.
2. Why is he unable to move his arms or legs? His face?
See answer to next item.
3. This problem is typically caused by obstruction in what artery?
Neurologists always start with localizing the lesion. First, this mans level of consciousness
is not impaired. He is awake and alert, as shown by the fact that he can understand
language and make correct yes/no answers. So, he could not have anything more than
limited damage to the brainstem, thalamus, or cerebral hemispheric cortex. He can move
his eyes vertically so the midbrain is largely intact, cranial nerves III and IV are intact, and

cortical regions directing this system are intact. Since he cannot move his eyes
horizontally, he has a lesion of the upper- to mid-pons, with bilateral involvement of the
MLF and/or PPRF. A lesion there would also explain his bilateral face/arm/leg weakness,
since it could involve the ventrally located corticospinal tracts bilaterally. Since both sides
are involved, the lesion has to involve a midline blood vessel or two separate lateral blood
vessels. Whenever possible, we try to explain neurological problems from a single lesion or
a single level of the neural axis. To do that here, the most common way to get a lesion like
this, and in this location, would be from an arterial obstruction at the distal tip of the
basilar artery (i.e. just before the origin of the posterior cerebral arteries).
4. Why is he still breathing?
The clot is in the distal basilar only. The proximal basilar, and the vertebral arteries that
feed it, are still intact, thus preserving the medualla and caudal pons.
His blood glucose concentration is normal. He is brought to the emergency department and
given intravenous tissue plasminogen activator. Over the next several hours he regains most of
the abilities he has lost, but remains unable to look to the left conjugately. However, his right
eye will adduct when he attempts to converge.
Questions:
1. What structures are involved in looking to the left?
(See answer to first question from Case I.) To look left, a signal starts in the right FEF,
directing the left PPRF to initiate a movement. The left PPRF directs the left VIth nucleus
to contract the left lateral rectus muscle, causing the left eyeball to abduct. At the same
time, via connections into the right MLF, the right IIIrd nucleus contracts the right medial
rectus muscle, causing the right eye to adduct.
2. Which structure(s) do you think are involved here?
The key here is that his right eye can adduct when he looks at an object close upduring
convergence. The fact that this occurs means that the right IIIrd nucleus and nerve and the
right medial rectus muscle all work just fine, and are all hooked up just fine. The problem
is that this intact system is not being driven during left lateral horizontal gaze. So, the
problem is with the PPRF-MLF system. Our thinking after that is a bit less clear, because
of the way the information we have is worded. If neither eye looks to the left, then this
patients pattern implies damage to the left PPRF. If only the right eye cannot look left on
horizontal gaze, then this patients pattern implies damage to the right MLF.
3. What structures are involved in convergence?
Convergence does not involve the MLF at all, since convergence is achieved by
simultaneous contraction of the medial rectus muscle of each eye. So, only the IIIrd cranial
nerve nucleus and this one target muscles need be intact on each side. The coordination is
done at the level of the dorsal midbrain. (Parinauds syndrome, described above, usually
also causes loss of convergence.)

Case III
A 27-year-old woman sees her physician because of dizziness and difficulty walking. She was
well until 7 years ago, when she had an episode of numbness in her legs, poor handwriting, and a
staggering gait, which resolved spontaneously over a 3-week period. She was well for the next 5
years, when she again developed some mild difficulty in walking. Again, she improved on her
own over a 2-weeks period and did well subsequently. She now presents with a 3-week history
of such severe dizziness that it has caused her to a fall several times. Over these past weeks, her
walking has deteriorated steadily, and she must now hold onto furniture in order to get around
her home. She also complains of double vision when looking off to her right side.
On her physical exam, during cranial nerve testing, the right optic disk appears paler than the
left. Her ocular motility is normal on left gaze. However, when she looks to the right, the right
eye develops some motor horizontal nystagmus, and the left eye does not completely adduct. On
motor examination, muscle tone is increased in the lower extremities; muscle bulk and power are
normal. Right ataxia is greater than left on finger to nose testing as well as on heel to shin
testing. The sensory examination shows some loss of vibratory perception and proprioception at
the toes. She sways when standing with her feet together, and swaying is made worse when she
closes her eyes. Her reflexes are brisk throughout, with bilateral extensor plantar responses. She
has a broad base when she walks and occasionally lurches to one side or the other. She is unable
to perform a tandem gait.
Questions:
1. What is nystagmus
Nystagmus is a rapid, involuntary, rhythmic jerking of an eyeball. In general, it represents
a cortical attempt to bring back the eyeball into the correct position. It can be
horizontal, vertical, or rotary. The most common kind of nystagmus is called jerk
nystagmus. In this kind, the eyeball moves slowly in one direction, and then rapidly in the
other direction. By convention, jerk nystagmus is described by the direction of the fast
phase (e.g. jerk nystagmus to the right means the eye moves slowly left and rapidly right).
See more in the answer to #2 next.
2. What problems might cause failure of adduction of the left eye?
This is most likely an internuclear ophthalmoplegia (INO), also known as an MLF
syndrome. Damage to the one MLF causes the eye on that side to fail to adduct during
horizontal gaze to the opposite direction. Classically, the normal eye shows horizontal
nystagmus. Since cranial nerve III and the medial rectus muscle themselves are
unaffected, the eye can still adduct during convergence. Since the MLF is densely
myelinated (think about why thats a good idea), it is a frequent target in multiple sclerosis,
a demyelinating disease of the central nervous system. Since it is in a vulnerable spot to be
infarcted by occlusions of tiny lateral penetrator arteries off of the basilar artery, it is also
frequently damaged by stroke.
3. Can you localize these problems to one place in the nervous system?
No. The patients symptoms and signs imply damage in multiple places in the nervous
systemone lesion cannot cause all these things. Starting with symptoms, she had bilateral

leg numbness. That requires bilateral involvement of sensory pathways, but that could be
anywhere from peripheral nerves up through sensory cortex of he brain. Poor right hand
control and unsteady gait sounds like a right cerebellar lesion. Alternatively, if this was
really weakness rather than dyscoordination it could have been due to a lesion to the
corticospinal tract subserving the right hemibody (i.e. right cervical cord, or left brain).
Dizziness could suggest vestibular dysfuction, which could be due to a peripheral inner ear
problem, VIIIth nerve or nucleus dysfunction, or caudal brainstem vestibular nuclei
dysfunction. She complains of diploplia when looking right, so either her left medial rectus
or right lateral rectus is failing to contract. In this patient, we should already suspect MS
(crudely defined as multiple CNS deficits separated by space and time), so we might
suspect a left INO causing left medial rectus failure on rightward gaze.
Turning to signs (i.e. exam findings), she had a left INO. So, there was damage in the
rostral pons involving the left MLF. She also has a pale right optic disk, implying
demyelination of the right optic nerve. She has bilateral upper motor neuron (UMN) signs
in her legs (increased tone, hyper-reflexia, upgoing toes) implying bilateral corticospinal
tract lesions in the thoracic cord (most likely to be there because there were no UMN signs
in her arms). Right greater than left hand ataxia confirms the above speculated right
cerebellar lesion. Bilateral posterior column involvement is suggested by the wide base
while walking (it decreases the need for proprioceptive feedback to keep one standing),
poor tandem walking, loss of vibratory and position sense, and positive Romberg sign.