Supranuclear Motility: Key Point

KEY POINT
128
Supranuclear
implies that the
lesion lies at or
above the level
of the ocular
motor nuclei
(ie, the nuclei
of the third,
fourth, and
sixth cranial
nerves).
Infranuclear
suggests that
the lesion
involves the
nucleus, nerve,
neuromuscular
junction, or
muscle.
SUPRANUCLEAR
MOTILITY
Gregory P. Van Stavern
ABSTRACT
The supranuclear ocular pathways are complex, but supranuclear motility disorders
are common and result in predictable localizable deficits. Careful history and
examination techniques allow for accurate diagnosis and will guide diagnostic
testing. This chapter will discuss the basic organization of the supranuclear ocular
motor system and cover the basic anatomy of cortical and brainstem pathways.
Specific examination techniques, as well as common clinical scenarios, will be
reviewed. Several relevant cases are included, along with videos on the CD-ROM
accompanying this issue demonstrating the relevant deficits.
Continuum Lifelong Learning Neurol 2009;15(4):128149.
OVERVIEW
The ocular motor system is arranged
in a hierarchical fashion, with topdown commands originating from cortical areas, and parallel inhibition and
modulation of descending pathways.
Knowledge of the specific anatomy
and physiology of eye movements has
advanced dramatically over the past
few decades, aided in part by advances
in neuroimaging. The details of the
neuroanatomy and neurophysiology at
or below the level of the ocular motor
nuclei (ie, the nuclei of cranial nerves
III, IV, and VI; the nerves proper;
neuromuscular junction; and extraocular muscles) have been studied fairly
well. The supranuclear pathways are
less well understood and are often a
source of confusion to clinical neurologists. All eye movement disorders can
be classified in terms of localizable
level of dysfunction (Table 9-1). It is
therefore incumbent upon the clinician to become familiar with the relevant neuroanatomy as well as the
specific examination techniques necessary for appropriate localization since

this aids immensely in deciding diagnostic and management strategies. The
evaluation and management of patients
with supranuclear eye movement disorders is often challenging, and the
examination techniques may be unfamiliar to some neurologists. We will review
the clinical neuroanatomy of the supranuclear ocular motor pathways and
highlight the survey with clinical cases.
TERMINOLOGY
A supranuclear ocular motility disorder is a condition that results from
damage to the cerebral or vestibular
pathways descending upon the ocular
motor nuclei (ie, the oculomotor, abducens, and trochlear nuclei). The term
may also include lesions involving the
pathways connecting the ocular motor
nuclei, such as the medial longitudinal
fasciculus (MLF). The ocular motor
nuclei directly control the extraocular
Relationship Disclosure: Dr Van Stavern has received personal compensation for activities with Pfizer Inc.
Unlabeled Use of Products/Investigational Use Disclosure: Dr Van Stavern has nothing to disclose.
Copyright # 2009, American Academy of Neurology. All rights reserved.
Copyright @ American Academy of Neurology. Unauthorized reproduction of this article is prohibited.
TABLE 9-1
Localization of Eye Movement Disorders
Brain Level
Ocular Motor Structure
Disorders Caused
by Lesions
Other Neurologic
Deficits
Cerebral cortex
Cortical gaze centers (eye fields)
Ipsilateral gaze deviation
Contralateral weakness
Hypometric saccades
Hemisensory loss
Impaired smooth pursuit

Basal ganglia
Descending gaze control

pathways
Saccadic intrusions
Axial rigidity
Impaired smooth pursuit
Dyskinesias
Hypometric saccades
Thalamus
Descending gaze control

pathways
Wrong-way deviation
Hemisensory loss
Thalamic esotropia
Visual field defect
Vertical gaze palsy
Contralateral hemiparesis
Superior oblique palsy
Light-near dissociation
Convergence-retraction
nystagmus
Contralateral tremor
? Vergence pathways
Midbrain
Vertical gaze centers (rostral

interstitial nucleus of medial
longitudinal fasciculus,
interstitial nucleus of Cajal)
Trochlear nucleus and fascicle
Oculomotor nucleus and fascicle Third nerve palsy

Pons
Abducens nucleus and fascicle

Paramedian pontine reticular
formation
Medial longitudinal fasciculus
Internuclear
ophthalmoplegia
Horizontal gaze palsy
Sixth nerve palsy
Facial nerve palsy

Trigeminal neuropathy
Hearing loss
Contralateral weakness
Skew deviation
muscles and receive input from descending cortical pathways as well as

direct input from the vestibular nuclei.
Eye movements are governed by
circuitry traversing multiple levels of
the neuraxis, and all of these eye movement centers are highly interdependent.
Primate models and clinical lesion-based
studies show that eye movements follow certain rules of behavior:
(1) Law of reciprocal innervation
(Sherrington law): This law states
that when an agonist muscle (eg,
lateral rectus) receives a neural
impulse to contract, an equivalent
inhibitory impulse is sent to motor
neurons supplying the appropriate
antagonist muscle (in the case of

the right lateral rectus, the right
medial rectus), resulting in relative
relaxation of the antagonists.
Although Sherrington (who
codified the law in the 1800s
based on experimental evidence)
proposed a stretch reflex in
the extraocular muscles as the
neural substrate for reciprocal
innervation, subsequent research
has not confirmed this theory.
Currently, the weight of evidence
implicates the organization of
brainstem connections as the
neural substrate for this law
(Sherrington, 1894).
Continuum Lifelong Learning Neurol 2009;15(4)
129
" SUPRANUCLEAR MOTILITY
(2) Law of motor correspondence

(Hering law): Conjugate eye
movements require coordinated
yoked pairing of extraocular
muscles. For example, accurate
horizontal movement to the right
requires combined contraction
of the right lateral and left medial
recti muscles. Since a primary goal
of normal eye movements is single
binocular vision, corresponding
yoked muscles must receive equal
innervation so that both eyes
move together. From a clinical
standpoint, this is a useful concept
and can be applied in patients
with acquired ocular motor nerve
palsies and eyelid disorders
(Hering, 1977) (Figure 9-1).
FUNCTIONAL CLASSES OF
EYE MOVEMENTS
Normal eye movements are a prerequisite to vision. The goal is to bring an
object of interest onto the fovea (the
portion of the retina subserving central

vision) and to hold it steadily. Allowable
retinal drift varies with the spatial frequency of the object being viewed
(58/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. Eye movements have been subdivided into different functional classes to help ensure
single, clear, binocular vision during all
activities (Table 9-2).
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 brains ability to determine retinal
image drift. These reflexes act as gazeholding mechanisms that stabilize gaze
and hold images steadily on the retina. It
130
The first patient (AC ) has a complete left abducens nerve palsy with a complete
left abduction defect. The second patient (DF) 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.
FIGURE 9-1
KEY POINT
TABLE 9-2
Functional Classes of Eye Movement
Class of Eye Movement Main Function

Vestibular
Gaze-holding: keeps images steady on the fovea

during brief head rotations
Fixation
Holds images of stationary objects upon the fovea
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 (physiologic)
Resets eyes during prolonged head rotation
Eye movements
are functionally
and anatomically
divided into
classes, most
of which are
interconnected
and are highly
dependent on
the afferent
visual system for
programming
and correction.
Adapted with permission from Leigh JR, Zee DS. The neurology of eye movements. 3rd ed. New York: Oxford
University Press, 1999:4.
makes intuitive sense, then, that the

afferent visual system (from the photoreceptor layer in the outer retina all the
way to the primary visual cortex) plays a
critical role in gaze-holding by providing
appropriate feedback regarding desired
and actual target position and eye position (Leigh and Zee, 1999).
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 gazeshifting and gaze-holding mechanisms,
with continuous feedback and reprogramming from the afferent visual system.
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 (such as saccades), a phasic increase, or pulse, of neural activity is
required. At eccentric positions in the
orbit, the eye must be held against the
elastic restoring forces acting to return
the globe to central position. This requires a tonic increase in neural activity:
the step of innervation. The pulse and
step must be correctly matched to produce an accurate eye movement and
steady fixation following it. There is
neurophysiologic evidence that the
position command (the step) is generated from the velocity command (the
pulse) by neural structures that integrate in a mathematical sense the
velocity-coded signals into positioncoded signals. This is referred to as the
neural integrator (Leigh and Zee, 1999;
Robinson, 1975). When the pulsestep
innervation is incorrectly programmed,
the eye is carried to a new position in
the orbit but cannot be held steadily
and drifts back toward central position.
This appears clinically as gaze-evoked
131
KEY POINT
The neural
integrator
integrates
information
regarding eye
position and
velocity to
match both to
desired eye
position and
accurate foveal
targeting.
This is a key
element of the
gaze-holding
system.
TABLE 9-3
132
nystagmus, with the fast phases representing corrective saccades.

SUPRANUCLEAR CONTROL OF
EYE MOVEMENTS
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 cortical control for eye movements has been researched extensively
over the years (Table 9-3). A large
amount of data has been derived from
experimental work in animals and clinical lesions in humans, but in the
past decade or so, additional information has been derived using functional
neuroimaging. In general, the pathways for horizontal eye movements
are better understood than those for
vertical eye movements, and for saccades better than for other classes of
eye movements. The frontal cortex
contains several areas responsible for
the initiation of horizontal saccades.
These include the frontal eye fields
(FEFs), the supplementary eye fields
(SEFs), and the dorsolateral prefrontal
cortex (DLPC). FEF neurons discharge
for voluntary saccades, memory-guided
saccades, and vergence movements. The
SEFs are involved in learned patterns of
ocular motor behavior, and the DLPC
controls planned saccades to remembered targets (Pierrot-Deseilligny et al,
2002). 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 and
initiating reflexive visually guided saccades. The FEF and PEF are heavily and
reciprocally interconnected (Figure 9-2).
Cortical and Subcortical Control of Saccades
Structure
Location/Brodmann Area
Function
Frontal eye fields
Anterior to premotor cortex;

Brodmann area 8
Initiates voluntary, nonvisually

guided, contraversive saccades
Parietal eye fields
Lateral bank of interparietal sulcus;

adjacent to Brodmann area 7a
Initiates voluntary, visually

guided, contraversive saccades
Supplementary eye fields
Anterior to supplementary motor

cortex (area 6), dorsal medial
frontal lobe
Involved in planning and learning

of saccadic movements
Dorsolateral prefrontal cortex
Dorsolateral frontal lobe;

Brodmann areas 9,46
Involved in memory-guided
saccades (saccades toward
remembered objects)
Superior colliculus
Caudal midbrain, posterior to

periaqueductal gray
Regulates excitatory and

inhibitory signals involved in
generation of saccades, and
control of eyehead movement

formation
Paracentral pons, anterior and

lateral to medial longitudinal
fasciculus
Directs projections to effector

extraocular muscles to move eye
Data from Leigh JR, Zee DS. The neurology of eye movements. 3rd ed. New York: Oxford University Press, 1999.
KEY POINT
The pathways
for horizontal
eye movements,
particularly
saccades
are well
understood.
Excitatory
signals descend
from the frontal
and parietal eye
centers and are
modulated as
they pass
through the
basal ganglia.
Cortical and subcortical pathways involved in the generation and modulation of

horizontal saccades (also see Table 9-3). The frontal and parietal eye fields
help initiate voluntary horizontal saccades. The control is contralateral:
signals from the left frontal eye fields and partial eye fields project downstream to the right
paramedian pontine reticular formation (PPRF), which contains burst neurons projecting to the
right abducens nucleus. Motor neurons in the abducens nucleus project to the right lateral rectus,
resulting in abduction of the right eye. Interneurons in the abducens nucleus project, primarily
through the medial longitudinal fasciculus, to the left medial rectus subnucleus, which causes
contraction of the left medial rectus and adduction of the left eye. The final result in a functioning
system is rapid, coordinated, high-velocity eye movements toward the right. Decreased firing
of omnipause neurons causes disinhibition of burst neurons in the PPRF, allowing transmission of
the signal. The descending signals are modulated by centers in the basal ganglia as well as
the superior colliculus.
FIGURE 9-2
The temporoparietooccipital (TPO)

junction is engaged in motion perception and smooth pursuit (tracking of
moving objects). It also plays a significant
role in visual fixation and gaze-holding.
Hemispheric control of horizontal
saccades is contralateral (ie, the right
hemisphere controls leftward saccades).
Signals arising from the FEF (predomi-
nately nonvisually guided saccades)

and the PEF (predominately visually
guided saccades) descend to the burst
cells of the contralateral paramedian
pontine reticular formation (PPRF). One
frontal pathway projects directly to the
PPRF, and another travels through the
caudate, substantia nigra, and superior colliculus (SC) before reaching the
133
KEY POINTS
Cerebral
control of eye
movements is
contralateral
for saccades
and ipsilateral
for smooth
pursuit.
The cellular
control of the
saccadic system
reflects a balance
between
excitatory and
inhibitory stimuli.
The burst
neurons are the
accelerator that
drives ocular
motor neurons,
and omnipause
neurons are
the brakes
that prevent
unwanted
and intrusive
saccades.
TABLE 9-4
134
PPRF. The pathways through the basal

ganglia maintain balance between reflexive and purposeful voluntary saccades and help prevent intrusive saccades. The PEF projects through the
SC to the PPRF.
Several cell populations play an
important role in saccadic control
(Table 9-4). Burst cells located in
the PPRF control the pulse of innervation required to move the eye against
the elastic forces in the orbit and
project to the motor neurons of the
ipsilateral abducens nucleus. Inhibitory neurons project to the contralateral
abducens 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 (Kim et al, 2007).
The abducens nucleus is the horizontal gaze center and receives commands for all functional classes of eye
movements. The motor neurons project to the ipsilateral lateral rectus, while
interneurons send axons that cross to
the contralateral MLF and ascend to the
contralateral medial rectus subnucleus
of the oculomotor complex.
Signals for eccentric gaze-holding

reach the abducens nucleus from the
ipsilateral nucleus prepositus hypoglossi
and medial vestibular nuclei. 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.
Saccadic disorders. Saccadic control is distributed between the frontal
and parietal lobes. Unilateral hemispheric lesions may reduce the accuracy and increase the latency of saccades while sparing saccadic velocity.
Acute bilateral frontal or large unilateral
frontoparietal lesions (usually ischemic
strokes) can transiently abolish voluntary saccades in any direction while sparing vestibulo-ocular responses. This syndrome is known as acquired oculomotor
apraxia. The parietal cortex mediates
saccades toward novel visual targets. Unilateral parietal lesions may cause delayed
hypometric contralateral saccades. This is
generally more prominent with rightsided (nondominant) lesions.
Clinical evaluation of saccades.
In clinic or at the bedside, voluntary
Cell Populations Involved in Saccadic Control
Cell Population
Location
Omnipause neurons Distributed throughout midbrain

and pons
Function
Exert tonic inhibitory effect on burst
neurons to prevent unwanted saccades
Burst neurons
Paramedian pontine reticular formation Control pulse of innervation to initiate

saccades; project to motor neurons
(horizontal), rostral interstitial nucleus
of medial longitudinal fasciculus
(vertical)
Motor neurons
Abducens nucleus (horizontal

movements), oculomotor and trochlear
nuclei (vertical movements)
Project directly to extraocular muscles to

initiate contraction
Interneurons
Abducens nucleus (horizontal

movements), oculomotor and trochlear
nuclei (vertical movements)
Connect ocular motor nuclei (cranial

nerves III, IV, VI) to produce conjugate
movements
saccades are assessed by asking the

patient to refixate between two targets
(such as the examiners fingers), usually 308 to 408 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
ipsilateral cerebellar system dysfunction. Saccadic hypometria indicates cerebral dysfunction but is otherwise
(in isolation) nonlocalizing. The anti-
saccade 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.
Smooth Pursuit
Smooth pursuit eye movements are
used to track objects moving in the
KEY POINTS
Saccadic
processing is
shared by
several cortical
areas and both
hemispheres,
so unilateral
hemispheric
dysfunction
generally
causes only
minor transient
saccadic deficits.
Saccades should
be tested for
accuracy and
speed by
having the
patient refixate
between two
targets about
408 apart.
135
A schematic diagram demonstrating cortical and subcortical pathways involved

in smooth pursuit. Retinal image motion produces signals passing through
the lateral geniculate nucleus to the striate cortex, as well as medial superior
temporal visual area (MST), middle temporal visual area (MT), posterior parietal cortex, and
the frontal eye fields (FEFs) and supplementary eye fields (SEFs). These areas project to the
cerebellum via the pontine nuclei. These cerebellar areas project to the ocular motor neurons
located in the ocular motor nuclei (III, IV, VI).
FIGURE 9-3
DLPN = dorsolateral pontine nucleus.

Adapted with permission from Leigh RJ, Zee DS. The neurology of eye movements. 3rd ed. New York: Oxford
University Press, 1999:165.
KEY POINTS
136
Cortical areas
in the medial
temporooccipital,
parietal, and
frontal lobes
participate in
the control of
smooth pursuit.
Symmetrically
abnormal
(saccadic)
smooth pursuit
is a nonspecific
marker of
generalized
cerebral
dysfunction.
Asymmetrically
impaired
smooth pursuit
suggests focal,
ipsilateral,
hemispheric
disease.
TABLE 9-5
Causes of
Symmetrically
Impaired Smooth
Pursuit
"
Sedative-Hypnotic
Medications
"
"
Anticonvulsants
"
Toxic-Metabolic
Encephalopathies
"
"
"
"
Advanced Age
Brainstem/Cerebellar
Dysfunction
Inattention
Fatigue
Basal Ganglia Disorders
Parkinson disease
Huntington disease
Wilson disease
Progressive supranuclear palsy
environment. The goal of the system is

to generate a smooth eye velocity that
matches the velocity of a visual target.
Visual motion processing drives pursuit. Smooth pursuit pathways are less
well understood than saccadic pathways, but a critical area, based on functional neuroimaging and lesion studies,
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. Axons descend from
the ipsilateral TPO junction and FEF
to the ipsilateral dorsolateral pontine nucleus (DLPN). Fibers cross and
reach the contralateral 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 (Figure 9-3).
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. Since this system
relies on widespread neural networking, it is vulnerable to dysfunction in
multiple areas of the brain. 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 (Table 9-5). 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 (Lekwuwa and Barnes, 1996).
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 108 to 408 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.
Vertical Eye Movement Control
Vertical saccades are generated bihemispherically, and signals descend
to the rostral interstitial nucleus of
the MLF (riMLF), located at the mesodiencephalic junction. The riMLF contains burst cells responsible for vertical
and torsional saccades. The riMLF projects to the motor neurons of the elevator
KEY POINT
Brainstem centers involved in vertical gaze control. The rostral interstitial

nucleus of the medial longitudinal fasciculus (riMLF) contains burst neurons
responsible for initiating upward, downward, and torsional saccades. The
pathways controlling upgaze pass more dorsally in the posterior commissure (PC) and are more
vulnerable to lesions in the dorsal midbrain.
FIGURE 9-4
INC = interstitial nucleus of Cajal; IO = inferior oblique; SR = superior rectus.
(superior rectus, inferior oblique) nuclei bilaterally, and the depressor (superior oblique, inferior rectus) nuclei
ipsilaterally.
The interstitial nucleus of Cajal
(INC) is located in the rostral midbrain
and may function as the neural integrator for vertical gaze. The INC receives
input necessary for vertical vestibular
and smooth pursuit movements from
the medulla and pons, largely conveyed
by the MLF (Dalezios et al, 1998). The
INC projects via the posterior commissure (PC) to motor neurons of cranial
nerves III and IV and to the contralateral INC (Scudder et al, 2002).
The PC crosses posterior to the
third ventricle at its junction with the
aqueduct, rostral to the SC. This pathway conveys crossing fibers of the INC
and receives axons from the nucleus
of the PC. The nucleus of the PC contributes to upgaze generation and coordination between eye and eyelid movements (Partsalis et al, 1994) (Figure 9-4).
Vestibular-Ocular System
The vestibulo-ocular reflex (VOR) produces conjugate eye movements that are
equal and opposite to head movements.
The VOR keeps gaze (the sum of eye

position and head position) stable relative to the visual world and ensures that
images remain stable on the fovea. The
VOR is anatomically and conceptually
divided into two components: (1) the
horizontal VOR and (2) the vertical and
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, although recent data from functional
neuroimaging have emerged (Dieterich
and Brandt, 2008). 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.
The horizontal VOR is produced
by projections from the horizontal
semicircular canals to the ipsilateral oculomotor nucleus and contralateral 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
Lesions involving
the posterior
commissure
initially involve
upgaze,
particularly
upward
saccadic
movements.
This results
from the more
dorsally placed
connections
from the rostral
interstitial
nucleus of
the medial
longitudinal
fasciculus
(riMLF) to
the elevator
subnuclei,
rendering
them more
vulnerable to
compressive
lesions.
137
KEY POINT
The integrity of
the vestibuloocular reflex
(VOR) is
dependent on
connections
between the
vestibular
nuclei and the
ocular motor
nuclei (third,
fourth, and
sixth cranial
nerve nuclei).
The VOR is a
major component
of the gaze-holding
system and helps
ensure that
objects of interest
remain steady
upon the fovea.
prepositus hypoglossi and the medial

vestibular nucleus, and then carried to
the medial and lateral rectus motor
neurons (Figure 9-5).
The vertical and torsional VOR are

generated by projections from the anterior and posterior semicircular canals to the oblique and vertical rectus
138
The excitatory connections of the horizontal vestibulo-ocular reflex. 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. Motor neurons in the
right abducens nucleus project directly to the right lateral rectus, resulting in abduction of the
right eye. Interneurons in the abducens nucleus project (through the medial longitudinal fasciculus)
to the contralateral medial rectus subnucleus, causing adduction of the left eye. The net result is
rightward eye movements in response to leftward head rotation (see also Figure 9-2).
FIGURE 9-5
muscles. Activation of both anterior

canals by downward head acceleration
induces the upward VOR, while activation of both posterior canals by upward head acceleration induces the
downward VOR. Contraction of the
ipsilateral superior rectus and contralateral inferior oblique, in response to
activation of the ipsilateral anterior
canal, results in elevation and contralateral torsion of both eyes. Contraction of the ipsilateral superior oblique
and contralateral inferior rectus, in response to activation of the posterior
canal, results in depression and contralateral 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
(Figure 9-6).
Implicit in the normal functioning
VOR is adequate cancellation of the
VOR 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.
Clinical evaluation of the vestibuloocular reflex. 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 bilateral VOR gain

abnormalities; the patients head is rotated left and right at 2 Hz to 3 Hz
while attempting to read the Snellen
visual acuity chart. Patients should wear
their usual and appropriate prescription while this test is performed. If VOR
139
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.
FIGURE 9-6
KEY POINTS
140
VOR gain can be

tested in clinic
using the
dynamic visual
acuity test and
the head
impulse test.
VOR balance
can be assessed
by looking for
spontaneous
nystagmus
after removal
of fixation.
Three regions of
the cerebellum
play important
roles in ocular
motor control:
(1) the flocculus
and paraflocculus
(floccular complex),
(2) the nodulus
and uvula
(nodulo-uvular
complex), and
(3) the dorsal
vermis and
fastigial nucleus.
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.
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
patients head and rapidly rotates the
head horizontally, about 208 to 308.
The VOR response elicited results from
excitation of the ipsilateral horizontal
semicircular canal. If VOR gain is normal, the patients 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.
TABLE 9-6
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 (see
the chapter on nystagmus).
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, whereas the
dorsal vermis and fastigial nuclei influence voluntary gaze shifting (Table 9-6).
Flocculus and paraflocculus. The
floccular complex helps generate smooth
pursuit and governs the neural integrator
Cerebellar Control of Eye Movements
Cerebellar Structure Function
Result of Lesion
Flocculus and
paraflocculus
Aids in generation of
smooth pursuit and helps
maintain eccentric gaze;
calibrates step-pulse ratio
of saccades
Saccadic smooth pursuit
Decreases duration of
vestibular responses;
inhibits velocity storage
Increased duration of
vestibular responses
Accelerates contraversive
saccades; involved in
coordination of smooth
pursuit
Hypometric contraversive
saccades
Tonic inhibitory control of

fastigial nucleus
Hypermetric
contraversive saccades
Nodulus and uvula
Fastigial nucleus
Dorsal vermis
Gaze-evoked nystagmus
Downbeat nystagmus
Periodic alternating
nystagmus
Hypermetric ipsiversive
saccades
Hypometric ipsiversive
saccades
Ipsilateral saccadic
smooth pursuit
in maintaining eccentric gaze (Lisberger

et al, 1984). 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 pulsestep ratio of saccades and the
amplitude of the VOR, adjusting them in
response to changes in the visual environment and visual needs.
Nodulus and uvula. The nodulus
and the adjacent uvula decrease the
duration of vestibular responses through
regulation of the velocity-storage system
in the vestibular nucleus (Choi et al,
2007). This system extends the decay
time of head velocity signals received
from the semicircular canals. The net
result is prolongation of the response
of the VOR to a constant head velocity
and enhancement of VOR gain at low
accelerations. Release of the stored
vestibular signal is required when it
conflicts with information from the
afferent visual system or with gravitational signals from the utricles. The
nodulus inhibits velocity storage, and
nodular lesions (around the roof of
the fourth ventricle) result in periodic
alternating nystagmus.
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 (Catz and
Thier, 2007). The fastigial nucleus accelerates contralateral saccades through
projections looping around the superior
cerebellar peduncle and terminating at
the contralateral PPRF. Lesions of the
fastigial nucleus (or projections) cause
hypometric contralateral saccades and
hypermetric ipsilateral saccades. Since
the fastigial nucleus is under inhibitory
control of the vermis, lesions of the
latter structure result in hypometric
ipsilateral and hypermetric contralateral saccades. Vermal lesions also impair smooth pursuit, usually toward
the side of the lesion.
HORIZONTAL GAZE DISORDERS

Horizontal Gaze Palsy
Abducens nucleus lesion. Damage
to the abducens nucleus results in an
obligate ipsilateral gaze palsy, evident
on examination as an inability to look
toward the side of the lesion. There is
an inability to activate the ipsilateral
lateral rectus and contralateral medial
rectus for all classes of eye movements, including vestibulo-ocular. 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. (See Case 9-1 with Video
Segment 51 of horizontal gaze palsy.)
formation 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 (dolls eye) in a PPRF lesion
is preserved, since vestibular fibers project directly to the abducens nucleus.
Etiologies are similar to abducens nerve
palsy (Figure 9-7).
Cerebral gaze palsy. Acute, unilateral hemispheric injury may cause
transient gaze palsy or gaze deviation.
This most often occurs with 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
KEY POINTS
Lesions of
the floccular
complex result
in saccadic
smooth pursuit,
impaired
cancellation of
the VOR, and
gaze-evoked,
rebound, and
downbeat
nystagmus.
Lesions of
the nodulus
prolong the
duration of
vestibular
responses and
may cause
periodic
alternating
nystagmus.
Lesions of the
paramedian
pontine
reticular
formation
(PPRF) or the
abducens
nucleus result
in an ipsilateral
gaze palsy.
Paresis of
horizontal gaze
with selective
involvement of
horizontal
saccades and
preservation of
VOR indicates
an ipsilateral
PPRF lesion.
141
KEY POINT
An ipsilateral
gaze deviation
from a cerebral
lesion usually
results in an
inability for the
patient to move
the eyes across
midline with
saccades or
smooth pursuit
but normal
horizontal
oculocephalic
responses.
Case 9-1
A 53-year-old woman presented with a 3-day history of left-sided weakness
and difficulty seeing toward the right with both eyes. Her neurologic
and neuro-ophthalmic examinations were significant for a mild left
hemiparesis and a partial right gaze palsy. MRI of the brain showed high
T2 signal in the right paramedian pons. Diffusion-weighted imaging was
consistent with acute ischemic stroke. Video Segment 51 demonstrates her
ocular motor examination. Note that vertical movements and vergence
were spared. All rightward eye movements were affected, implicating
the right abducens nucleus rather than the PPRF (see discussion relating
to PPRF). Also note the contralateral gaze-evoked nystagmus with a
prominent rebound component.
Comment. Damage to the abducens nucleus results in an ipsilateral
obligate gaze paresis for all classes of eye movements. The usual cause is
ischemic or hemorrhagic stroke, but demyelination, tumor, and vascular
malformation are other potential causes.
be distinguished from gaze apraxia,

which implies difficulty initiating visually
guided saccades. Other localizing features, such as hemineglect, visual field
defect, and anosognosia are often pres-
ent. The most common causes are

stroke and tumor.
Internuclear ophthalmoplegia.
Lesions of the MLF may result in impaired adduction during conjugate gaze
142
The effect of lesions on horizontal eye movements. A lesion of the right

paramedian pontine reticular formation (PPRF) (1) results in selective loss of
rightward horizontal saccades. The horizontal vestibulo-ocular reflex (VOR) is
spared and vergence movements are preserved. Damage to the right abducens nucleus (2) results
in an obligate right gaze palsy. All eye movements, including VOR and vergence, are involved.
A lesion of the left medial longitudinal fasciculus (3) results in a left adduction deficit, which may
cause a frank adduction defect, or simply slow adducting rightward saccade (adduction lag).
FIGURE 9-7
IN = interneurons; MN = motor neurons.
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 (Zee
et al, 1987). Subtle INO may manifest as
a slowing of adducting saccades 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 (inferior rectus, superior rectus, inferior
oblique weakness, ptosis, pupillary size
and reaction) and the preservation, in
some cases, of medial rectus function
during convergence. Many patients with
a unilateral INO do not report diplopia
in primary gaze as there is typically only
minimal misalignment in this position.
Bilateral INO may cause a large exotropia (eyes turned out) known as walleyed 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 most common cause is
neoplasm, followed closely by 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. (See Case 9-2 with
Video Segment 52 of bilateral INO.)
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 (see later discussion) 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. Associated localizing
features, such as facial and trigeminal
nerve palsy and contralateral hemiplegia, may be present. Etiologies include
ischemia, demyelination, and tumor.
(See Case 9-3 with Video Segment
54 of one-and-a-half syndrome.)
Thalamic esotropia and wrongway deviation. Thalamic lesions (usually
hemorrhagic) may cause horizontal gaze
KEY POINT
The most
sensitive sign of
an internuclear
ophthalmoplegia
is ipsilateral
slowing of
adducting
saccades (ie,
adduction lag).
This may be
present even in
the setting of
normal or
nearly normal
adduction.
Case 9-2
A 41-year-old man presented to the neuro-ophthalmology clinic with
a 1-week history of diplopia. The diplopia began soon after he returned
from a trip to Las Vegas and was described as constant, binocular, and
associated with mild gait instability. His neuro-ophthalmic examination
was notable for mild bilateral adduction defects and abducting nystagmus.
Video Segment 52 demonstrates his ocular motor findings. Note that the
adduction defect is partial, and he has prominent bilateral adduction lag,
the most sensitive sign of INO. MRI of the brain demonstrated an enhancing
demyelinating plaque in the dorsal pons and two periventricular T2 bright
signals, consistent with asymptomatic previous demyelination.
Comment. INO, either unilateral or bilateral, is a common presenting
feature of multiple sclerosis. It is important to note that the adduction
defect may be subtle, and the presence of slowed adducting saccades
confirms INO as the etiology. The presence of abducting nystagmus
is nonspecific and may be seen in pseudo-INO due to myasthenia
gravis. This may reflect central adaptation or an application of Hering law,
with increased innervation to both the weak medial rectus and normal
lateral rectus.
143
Case 9-3
A 44-year-old woman presented with a 2-day history of diplopia and
right-sided numbness. Her medical history was benign, and she had no
history of previous neurologic events. Her general neurologic examination
was notable for patchy predominately right-sided hemisensory loss. Her
neuro-ophthalmic examination was remarkable for nearly complete
ophthalmoplegia, with the only surviving eye movement being right
abduction. Video Segment 54 shows the relevant findings. Note the lack
of ptosis and the preserved vertical movements. MRI demonstrated a
large ring-enhancing lesion in the left paramedian pons with multiple,
predominately periventricular T2 bright signal, compatible with extensive
demyelinating disease.
Comment. One-and-a-half syndrome (one whole gaze palsy and
one half of a gaze palsy) results from a lesion in the paramedian pons.
This has also been termed paramedian pontine exotropia. All classes
of eye movements include an ipsilateral gaze palsy (resulting from
involvement of the ipsilateral abducens nucleus) and an ipsilateral INO,
secondary to damage to the MLF. The only residual intact eye movement
therefore is abduction contralateral to the lesion. Common etiologies
include stroke and demyelination.
144
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 (Messe
and Cucchiara, 2003). 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.
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

(Table 9-7).
TABLE 9-7
"
Localization of
Vertical Gaze Palsy
Paresis of Downgaze
Selective loss of downward
saccades: bilateral riMLF
Loss of all forms of vertical
eye movements: INC or PC
"
Paresis of Upgaze
Loss of all forms of vertical
eye movements: PC and INC
Convergence-retraction
nystagmus with upward
saccades: PC
"
Complete Vertical Gaze Palsy

Selective loss of vertical
saccades: bilateral riMLF
INC or PC
riMLF = rostral interstitial nucleus of

the medial longitudinal fasciculus;
INC = interstitial nucleus of Cajal;
PC = posterior commissure.
Bilateral riMLF lesions (eg, infarction

in the territory of the posterior thalamicsubthalamic artery) produce abnormal
vertical saccades. Lesions of the INC
impair vertical gaze-holding and may be
associated with torsional nystagmus.
Parinaud syndrome (dorsal midbrain syndrome) results from damage to the PC. Characteristic features
include limitation of upward eye movements, tonic sustained downgaze (settingsun sign), and mid-dilated pupils displaying light-near dissociation (due to
involvement of the pretectal nuclei)
(Keane, 1990). 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 (Video Segment 56).
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.
Bell phenomenon refers to the upward and often oblique 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.
Skew and ocular tilt reaction.
Skew deviation is an acquired vertical
misalignment caused by disturbance of
prenuclear vestibular input. Since ascending vestibular fibers traverse the
medulla, pons, and midbrain, skew
is often accompanied by other signs
of brainstem dysfunction (such as an

INO). Skew may be comitant (ie, a deviation that is the same amount in all
directions of gaze) or noncomitant.
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 (Parulekar
et al, 2008).
The ocular tilt reaction (OTR) consists of head tilt, ocular torsion, and
skew deviation. The head tilt is toward
the side of the lower ear, and the
upper poles of the eyes are rotated
toward that side as well. OTR reflects
imbalance of otolith inputs and may
represent a lesion anywhere from the
contralateral otoliths in the inner ear
to the ipsilateral INC. Peripheral and
lower brainstem lesions cause ipsilateral OTR, whereas pontine and midbrain lesions cause contralateral OTR.
Skew and OTR may be seen in a variety
of disorders of the brainstem and
cerebellum or as a transient phenomenon with elevated intracranial pressure (Brodsky et al, 2006).
KEY POINT
Lesions involving
the riMLF
generally impair
vertical
saccades but
spare vestibular
responses and
smooth pursuit.
Therefore,
assessment of
vertical gaze
using only
smooth pursuit
may miss a
saccadic vertical
gaze palsy.
SUPRANUCLEAR
MOTILITY DISORDERS
IN SPECIFIC DISEASES
Neurodegenerative diseases often result in visual dysfunction. The supranuclear motility system is selectively
involved in certain conditions, such as
Parkinson disease (PD) and progressive
supranuclear palsy (PSP). This may in
145
KEY POINT
146
Convergence
insufficiency is
a common
cause of
diplopia in
patients with
Parkinson
disease.
Accurate
recognition
and diagnosis
prevent
unnecessary
diagnostic
testing
and guide
appropriate
treatment.
part relate to the influence (usually

inhibitory) of the basal ganglia on the
descending supranuclear pathways. In
some patients, visual symptoms may
occur early in the disease course and be
one of the presenting features. Careful
assessment of the ocular motor system
can identify the cause of the visual symptoms and provide valuable clues when
the specific diagnosis is in question.
Parkinson Disease
PD is a primary neurodegenerative disorder characterized pathologically by
loss of dopaminergic cells within the
substantia nigra and clinically by resting
tremor, bradykinesia, and rigidity. The
precise etiology is unknown, and treatment is largely symptomatic, most commonly with dopaminergic agonists, such
as levodopa.
Visual symptoms are frequently present in patients with PD but are rarely a
presenting feature. Visual hallucinations
occur in up to 25% of patients with PD;
this may occur as a result of dopaminergic medications or visual cortical
dysfunction (Biousse et al, 2004). Other
symptoms may be relatively vague, requiring direct and specific questioning
to clarify.
Eyelid disorders are common in PD.
Decreased blink rate is frequent, resulting in dry eye and assorted afferent
visual symptoms. Blepharospasm can
occur as well, possibly due to disinhibition of the facial nucleus and spontaneous firing of orbicularis oculi muscles.
Apraxia of eyelid opening occurs less
frequently; in this condition, the patient
has difficulty initiating opening of the
eyelids. Lepore and Duvoisin (1985) reported the clinical criteria for the diagnosis of apraxia of eyelid opening
as transitory inability to initiate eyelid
opening; no evidence of ongoing orbicularis oculi contraction, such as lowering of the brows beneath the superior
orbital margins (Charcot eyebrow sign
of blepharospasm), vigorous frontalis
contraction during periods of inability

to raise eyelids, no oculomotor or ocular sympathetic nerve dysfunction, and
no ocular myopathy.
The supranuclear ocular motor system is affected in PD. Convergence is
impaired in many patients, resulting
in convergence insufficiency (CI). Indeed, CI should be a leading consideration in PD patients with diplopia.
Historical features supporting CI include 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. Examination findings confirming CI include
reduced convergence amplitudes, remote near point of convergence, and
exodeviation at near. Correct diagnosis in the appropriate clinical setting
would obviate the need for extensive
workup for alternate causes. Treatment
usually involves adequate presbyopic correction and prisms.
The clinical features of most patients
presenting with PD are prolonged saccadic latency, hypometric saccades, and
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; they are
rarely symptomatic (Pelak and Hall, 2004).
Progressive Supranuclear Palsy
PSP, the most common of the Parkinsonplus neurodegenerative disorders, has
prominent neuro-ophthalmic findings
(Steele et al, 1964). Current diagnostic criteria include gradually progressive disorder, onset at age older than
40, either vertical supranuclear palsy
or both slowing of vertical saccades
and postural instability with falls in the
first year of onset. Patients with PSP have
parkinsonian features, such as decreased

blink rate, masked facies, axial rigidity,
and en bloc turns, and may initially be
mistakenly diagnosed with PD. However,
clues to the diagnosis include greater
axial and neck rigidity, marked micrographia, frequent spastic dysarthria and
dysphonia, lack of resting tremor, eye
movement abnormalities, and minimal
response to dopaminergic therapy.
As suggested by the name of the
condition, the supranuclear eye movement system is often abnormal in PSP.
The ocular motor findings are often
present early in the disease course and
may help in differentiating PSP from PD
and other causes of parkinsonism.
Saccades in PSP are initially slowed.

The classic abnormality is supranuclear gaze paresis, initially for vertical
eye movements but ultimately affecting eye movements in all planes. Patients may progress to complete
ophthalmoplegia. The VOR remains intact until late in the disease course.
Frequent or continuous square-wave
jerks are commonly seen and are more
frequent in PSP than PD. The ratio of
square-wave jerks to blink rate may
help distinguish PSP from idiopathic
PD (Altiparmak et al, 2006).
Eyelid disorders are common in PSP,
similar to PD. Decreased blink rate is common and results in dry eyes, occasionally
KEY POINT
The visual
manifestations
of progressive
supranuclear
palsy are similar
to Parkinson
disease but
differ in terms
of direction
of saccadic
slowing,
frequency
of saccadic
intrusions,
and ratio of
square-wave
jerks to
blink rate.
Case 9-4
A 72-year-old man presented with a 5-year history of PSP. He had originally
developed axial rigidity and gait instability 5 years earlier. He began
noticing frequent contraction of his eyelids 3 years earlier and had been
receiving botulinum toxin injections for blepharospasm. He also reported
impaired reading for the past several years. He had to hold reading
material up close to his eyes to read effectively. His rigidity had responded
minimally to dopaminergic medications.
Previous evaluation had included neuroimaging, which was
unremarkable, and a variety of blood tests, including antinuclear antibody,
serum ceruloplasmin, rapid plasma reagent, erythrocyte sedimentation
rate, and liver enzymes, all of which were unremarkable.
Neuro-ophthalmic examination showed best corrected distance visual
acuity of 20/25 and near visual acuity of 20/25 OU. Video Segment 55
demonstrates salient features of his external and ocular motor examination:
he had nearly complete limitation of saccades and smooth pursuit in the
horizontal plane, with complete limitation of saccades and smooth pursuit
in the vertical plane. The horizontal limitation was overcome completely
with horizontal oculocephalics, the vertical limitation only incompletely
overcome (not shown in video). He had frequent, bilateral, synchronized
contraction of orbicularis oculi muscles, consistent with blepharospasm.
He had some apraxia of eyelid opening. No measurable convergence
was present. The remainder of his neuro-ophthalmic examination was
unremarkable.
Comment. This patient has advanced PSP. Note the nearly complete
ophthalmoplegia. His visual symptoms were multifactorial: the reading
impairment was related to the blepharospasm, the inability to look down
to read (due to loss of downgaze), and severe convergence insufficiency.
He was switched from botulinum toxin type A to type B and was given a
reading platform to eliminate need for downgaze. He was also referred
to a multidisciplinary visual rehabilitation service.
147
severe. Blepharospasm and apraxia of

eyelid opening may occur as well. (See
Case 9-4 with video of PSP patient.)
Treatment for the visual symptoms
of both PD and PSP are symptomatic.
Dry eye should be treated aggressively
with lubricating drops and ointments,
and punctal plugs for refractory patients. Convergence insufficiency can
be treated successfully with base-in
prism placed over reading glasses to
help fusion, although the poor fu-
sional ability of most patients with PSP

often renders prisms less useful. Botulinum toxin is the treatment of choice
for symptomatic blepharospasm and has
been used successfully for apraxia of
eyelid opening as well (Jankovic, 1995)
Multidisciplinary low-vision services employing optometrists, physical therapists, and occupational therapists can
be useful, particularly if associated ophthalmic conditions (such as age-related
macular degeneration) are present.
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rates to blink rates distinguishes progressive supranuclear palsy from Parkinson disease.
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Biousse V, Skibell BC, Watts RL, et al. Ophthalmologic features of Parkinsons disease.
Neurology 2004;62(2):177180.
Brodsky MC, Donahue SP, Vaphiades M, Brandt T. Skew deviation revisited. Surv
Ophthalmol 2006;51(2):105128.
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Supranuclear Motility: Key Point

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KEY POINT

specific examination techniques necessary for appropriate localization since

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Localization of Eye Movement Disorders

Ocular Motor Structure

Cortical gaze centers (eye fields)

Ipsilateral gaze deviation

Impaired smooth pursuit

Descending gaze control

Impaired smooth pursuit

Descending gaze control

Visual field defect

Vertical gaze palsy

Superior oblique palsy

Vertical gaze centers (rostral

Oculomotor nucleus and fascicle Third nerve palsy

Abducens nucleus and fascicle

Facial nerve palsy

muscles and receive input from descending cortical pathways as well as

antagonist muscle (in the case of

Copyright @ American Academy of Neurology. Unauthorized reproduction of this article is prohibited.