Supranuclear Motility.11

SUPRANUCLEARMOTILITYGregory P. Van Stavern

ABSTRACT

The supranuclear ocular pathways are complex, but supranuclear motility disordersare common and result in predictable localizable deficits. Careful history andexamination techniques allow for accurate diagnosis and will guide diagnostictesting. This chapter will discuss the basic organization of the supranuclear ocularmotor system and cover the basic anatomy of cortical and brainstem pathways.Specific examination techniques, as well as common clinical scenarios, will bereviewed. Several relevant cases are included, along with videos on the CD-ROMaccompanying this issue demonstrating the relevant deficits.

Continuum Lifelong Learning Neurol 2009;15(4):128–149.

OVERVIEW

The ocular motor system is arrangedin a hierarchical fashion, with top-down commands originating from cor-tical areas, and parallel inhibition andmodulation of descending pathways.Knowledge of the specific anatomyand physiology of eye movements hasadvanced dramatically over the pastfew decades, aided in part by advancesin neuroimaging. The details of theneuroanatomy and neurophysiology ator below the level of the ocular motornuclei (ie, the nuclei of cranial nervesIII, IV, and VI; the nerves proper;neuromuscular junction; and extraoc-ular muscles) have been studied fairlywell. The supranuclear pathways areless well understood and are often asource of confusion to clinical neurol-ogists. All eye movement disorders canbe classified in terms of localizablelevel of dysfunction (Table 9-1). It istherefore incumbent upon the clini-cian to become familiar with the rel-evant neuroanatomy as well as the

specific examination techniques neces-sary for appropriate localization sincethis aids immensely in deciding diag-nostic and management strategies. Theevaluation and management of patientswith supranuclear eye movement dis-orders is often challenging, and theexamination techniques may be unfamil-iar to some neurologists. We will reviewthe clinical neuroanatomy of the supra-nuclear ocular motor pathways andhighlight the survey with clinical cases.

TERMINOLOGY

A supranuclear ocular motility disor-der is a condition that results fromdamage to the cerebral or vestibularpathways descending upon the ocularmotor nuclei (ie, the oculomotor, ab-ducens, and trochlear nuclei). The termmay also include lesions involving thepathways connecting the ocular motornuclei, such as the medial longitudinalfasciculus (MLF). The ocular motornuclei directly control the extraocular

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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.

KEY POINT

A 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.

Copyright # 2009, American Academy of Neurology. All rights reserved.

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

muscles and receive input from de-scending cortical pathways as well asdirect input from the vestibular nuclei.

Eye movements are governed bycircuitry traversing multiple levels ofthe neuraxis, and all of these eye move-ment centers are highly interdependent.Primate models and clinical lesion-basedstudies show that eye movements fol-low certain rules of behavior:

(1) Law of reciprocal innervation(Sherrington law): This law statesthat when an agonist muscle (eg,lateral rectus) receives a neuralimpulse to contract, an equivalentinhibitory impulse is sent to motorneurons supplying the appropriate

antagonist muscle (in the case ofthe right lateral rectus, the rightmedial rectus), resulting in relativerelaxation of the antagonists.Although Sherrington (whocodified the law in the 1800sbased on experimental evidence)proposed a stretch reflex inthe extraocular muscles as theneural substrate for reciprocalinnervation, subsequent researchhas not confirmed this theory.Currently, the weight of evidenceimplicates the organization ofbrainstem connections as theneural substrate for this law(Sherrington, 1894).

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TABLE 9-1 Localization of Eye Movement Disorders

Brain Level Ocular Motor StructureDisorders Causedby Lesions

Other NeurologicDeficits

Cerebral cortex Cortical gaze centers (eye fields) Ipsilateral gaze deviation Contralateral weakness

Hypometric saccades Hemisensory loss

Impaired smooth pursuit

Basal ganglia Descending gaze controlpathways

Saccadic intrusions Axial rigidity

Impaired smooth pursuit Dyskinesias

Hypometric saccades

Thalamus Descending gaze controlpathways

Wrong-way deviation Hemisensory loss

? Vergence pathwaysThalamic esotropia Visual field defect

Midbrain Vertical gaze centers (rostralinterstitial nucleus of mediallongitudinal fasciculus,interstitial nucleus of Cajal)

Vertical gaze palsy Contralateral hemiparesis

Trochlear nucleus and fascicle

Superior oblique palsy Light-near dissociation

Oculomotor nucleus and fascicle

Convergence-retractionnystagmus

Contralateral tremor

Third nerve palsy

Pons Abducens nucleus and fascicle Internuclearophthalmoplegia

Facial nerve palsy

Paramedian pontine reticularformation Horizontal gaze palsy

Trigeminal neuropathy

Medial longitudinal fasciculus Sixth nerve palsyHearing loss

Skew deviationContralateral weakness

Continuum Lifelong Learning Neurol 2009;15(4)


(2) Law of motor correspondence(Hering law): Conjugate eyemovements require coordinated‘‘yoked’’ pairing of extraocularmuscles. For example, accuratehorizontal movement to the rightrequires combined contractionof the right lateral and left medialrecti muscles. Since a primary goalof normal eye movements is singlebinocular vision, correspondingyoked muscles must receive equalinnervation so that both eyesmove together. From a clinicalstandpoint, this is a useful conceptand can be applied in patientswith acquired ocular motor nervepalsies and eyelid disorders(Hering, 1977) (Figure 9-1).

FUNCTIONAL CLASSES OFEYE MOVEMENTS

Normal eye movements are a prereq-uisite to vision. The goal is to bring anobject of interest onto the fovea (the

portion of the retina subserving centralvision) and to hold it steadily. Allowableretinal drift varies with the spatial fre-quency of the object being viewed(58/s for standard visual acuity charts).Excess retinal motion degrades visualacuity and may cause oscillopsia (illu-sory movement of the visual environ-ment). Since head perturbations arefrequent during normal activities (suchas walking), compensatory mechanismshave evolved to prevent retinal drift withhead and body movements. Eye move-ments have been subdivided into dif-ferent functional classes to help ensuresingle, clear, binocular vision during allactivities (Table 9-2).

Vestibulo-ocular reflexes depend onthe ability of the labyrinthine mechano-receptors to detect head accelerations,while visually mediated reflexes (optoki-netic and smooth pursuit systems) relyon the brain’s ability to determine retinalimage drift. These reflexes act as gaze-holding mechanisms that stabilize gazeand hold images steadily on the retina. It

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FIGURE 9-1 The first patient (A–C ) has a complete left abducens nerve palsy with a completeleft abduction defect. The second patient (D–F) has a complete right abducenspalsy with complete right abduction defects. Although both patients have

complete abduction defects with equally weak affected lateral recti, note that in primary gazethe first patient has a smaller angle esotropia (one eye deviated inward) than the second. Thereason is that the first patient is fixing with the normal eye, and the innervation to the weaklateral rectus remains low. The second patient is attempting to fix with the weak eye, and theinnervation 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 alsoincreased, 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 falseconclusion that the patient has worsened. This is a clinical application of Hering law.


"SUPRANUCLEAR MOTILITY


makes intuitive sense, then, that theafferent visual system (from the photo-receptor layer in the outer retina all theway to the primary visual cortex) plays acritical role in gaze-holding by providingappropriate feedback regarding desiredand actual target position and eye po-sition (Leigh and Zee, 1999).

Saccades are rapid conjugate eyemovements that redirect fixation sothat a new object of interest falls ontothe fovea. Vergences are dysconjugatemovements (ie, the eyes are movingin opposite directions) that shift gazebetween far and near targets (conver-gence and divergence). Both of thesesystems act as gaze-shifting mecha-nisms, which aim to bring new objectsof interest onto the fovea. Normal eyemovements can then be conceivedin terms of a balance between gaze-shifting and gaze-holding mechanisms,with continuous feedback and repro-gramming from the afferent visual system.

ORBITAL MECHANICS ANDSTEP-PULSE INNERVATION

The elastic structures in the orbit sup-port the globe and impose amechanical

restraint on gaze control. To overcomethe viscous drag of supporting tissues, astrong contraction of the extraocularmuscles is required. For rapid move-ments (such as saccades), a phasic in-crease, or ‘‘pulse,’’ of neural activity isrequired. At eccentric positions in theorbit, the eye must be held against theelastic restoring forces acting to returnthe globe to central position. This re-quires a tonic increase in neural activity:the step of innervation. The pulse andstep must be correctly matched to pro-duce an accurate eye movement andsteady fixation following it. There isneurophysiologic evidence that theposition command (the step) is gener-ated from the velocity command (thepulse) by neural structures that in-tegrate in a mathematical sense thevelocity-coded signals into position-coded signals. This is referred to as theneural integrator (Leigh and Zee, 1999;Robinson, 1975). When the pulse–stepinnervation is incorrectly programmed,the eye is carried to a new position inthe orbit but cannot be held steadilyand drifts back toward central position.This appears clinically as gaze-evoked

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TABLE 9-2 Functional Classes of Eye Movement

Class of Eye Movement Main Function

Vestibular Gaze-holding: keeps images steady on the foveaduring brief head rotations

Fixation Holds images of stationary objects upon the fovea

Optokinetic Keeps images stable on retina during prolongedsustained head rotations

Smooth pursuit Holds images of small moving targets steady uponthe fovea

Saccades Brings objects of interest onto the fovea

Vergence Moves eyes in opposite directions to bring imagesof a single object onto the fovea

Nystagmus (physiologic) Resets eyes during prolonged head rotation

Adapted with permission from Leigh JR, Zee DS. The neurology of eye movements. 3rd ed. New York: OxfordUniversity Press, 1999:4.

KEY POINT

A 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.



nystagmus, with the fast phases repre-senting corrective saccades.

SUPRANUCLEAR CONTROL OFEYE MOVEMENTS

Saccadic Control

The cerebral cortex participates in thecontrol of all classes of eye movements.In general, reflexive stimulus-boundeye movements originate in posteriorportions of the brain, while voluntarymovements arise from frontal areas.

The cortical control for eye move-ments has been researched extensivelyover the years (Table 9-3). A largeamount of data has been derived fromexperimental work in animals and clin-ical lesions in humans, but in thepast decade or so, additional informa-tion has been derived using functionalneuroimaging. In general, the path-ways for horizontal eye movementsare better understood than those for

vertical eye movements, and for sac-cades better than for other classes ofeye movements. The frontal cortexcontains several areas responsible forthe initiation of horizontal saccades.These include the frontal eye fields(FEFs), the supplementary eye fields(SEFs), and the dorsolateral prefrontalcortex (DLPC). FEF neurons dischargefor voluntary saccades, memory-guidedsaccades, and vergencemovements. TheSEFs are involved in learned patterns ofocular motor behavior, and the DLPCcontrols planned saccades to remem-bered targets (Pierrot-Deseilligny et al,2002). The posterior parietal region isinvolved in shifting gaze toward novelobjects of interest and modulating spa-tial attention. The parietal eye fields(PEFs) project to the FEFs and areinvolved in exploring visual scenes andinitiating reflexive visually guided sac-cades. The FEF and PEF are heavily andreciprocally interconnected (Figure 9-2).

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TABLE 9-3 Cortical and Subcortical Control of Saccades

Structure Location/Brodmann Area Function

Frontal eye fields Anterior to premotor cortex;Brodmann area 8

Initiates voluntary, non–visuallyguided, contraversive saccades

Parietal eye fields Lateral bank of interparietal sulcus;adjacent to Brodmann area 7a

Initiates voluntary, visuallyguided, contraversive saccades

Supplementary eye fields Anterior to supplementary motorcortex (area 6), dorsal medialfrontal lobe

Involved in planning and learningof saccadic movements

Dorsolateral prefrontal cortex Dorsolateral frontal lobe;Brodmann areas 9,46

Involved in memory-guidedsaccades (saccades towardremembered objects)

Superior colliculus Caudal midbrain, posterior toperiaqueductal gray

Regulates excitatory andinhibitory signals involved ingeneration of saccades, andcontrol of eye–head movement

Paramedian pontine reticularformation

Paracentral pons, anterior andlateral to medial longitudinalfasciculus

Directs projections to effectorextraocular 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

A 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.




The temporoparietooccipital (TPO)junction is engaged in motion percep-tion and smooth pursuit (tracking ofmoving objects). It also plays a significantrole in visual fixation and gaze-holding.

Hemispheric control of horizontalsaccades is contralateral (ie, the righthemisphere controls leftward saccades).Signals arising from the FEF (predomi-

nately non–visually guided saccades)and the PEF (predominately visuallyguided saccades) descend to the burstcells of the contralateral paramedianpontine reticular formation (PPRF). Onefrontal pathway projects directly to thePPRF, and another travels through thecaudate, substantia nigra, and supe-rior colliculus (SC) before reaching the

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FIGURE 9-2 Cortical and subcortical pathways involved in the generation and modulation ofhorizontal saccades (also see Table 9-3). The frontal and parietal eye fieldshelp initiate voluntary horizontal saccades. The control is contralateral:

signals from the left frontal eye fields and partial eye fields project downstream to the rightparamedian pontine reticular formation (PPRF), which contains burst neurons projecting to theright 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, primarilythrough the medial longitudinal fasciculus, to the left medial rectus subnucleus, which causescontraction of the left medial rectus and adduction of the left eye. The final result in a functioningsystem is rapid, coordinated, high-velocity eye movements toward the right. Decreased firingof omnipause neurons causes disinhibition of burst neurons in the PPRF, allowing transmission ofthe signal. The descending signals are modulated by centers in the basal ganglia as well asthe superior colliculus.

KEY POINT

A 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.



PPRF. The pathways through the basalganglia maintain balance between re-flexive and purposeful voluntary sac-cades and help prevent intrusive sac-cades. The PEF projects through theSC to the PPRF.

Several cell populations play animportant role in saccadic control(Table 9-4). Burst cells located inthe PPRF control the pulse of innerva-tion required to move the eye againstthe elastic forces in the orbit andproject to the motor neurons of theipsilateral abducens nucleus. Inhibito-ry neurons project to the contralateralabducens nucleus. Omnipause neu-rons are distributed throughout thebrainstem, project to burst cells, andexert a tonic inhibitory effect. Theyprimarily act to prevent unwanted andintrusive saccades (Kim et al, 2007).

The abducens nucleus is the hori-zontal gaze center and receives com-mands for all functional classes of eyemovements. The motor neurons proj-ect to the ipsilateral lateral rectus, whileinterneurons send axons that cross tothe contralateral MLF and ascend to thecontralateral medial rectus subnucleusof the oculomotor complex.

Signals for eccentric gaze-holdingreach the abducens nucleus from theipsilateral nucleus prepositus hypoglossiandmedial vestibular nuclei. These struc-tures and their cerebellar connectionsserve as the neural integrator for hori-zontal gaze-holding. They provide theeye position signal necessary to holdthe eye steady in eccentric position inthe orbit.

Saccadic disorders. Saccadic con-trol is distributed between the frontaland parietal lobes. Unilateral hemi-spheric lesions may reduce the accu-racy and increase the latency of sac-cades while sparing saccadic velocity.Acute bilateral frontal or large unilateralfrontoparietal lesions (usually ischemicstrokes) can transiently abolish volun-tary saccades in any direction while spar-ing vestibulo-ocular responses. This syn-drome is knownasacquired oculomotorapraxia. The parietal cortex mediatessaccades toward novel visual targets. Uni-lateral parietal lesions may cause delayedhypometric contralateral saccades. This isgenerally more prominent with right-sided (nondominant) lesions.

Clinical evaluation of saccades.In clinic or at the bedside, voluntary

134

TABLE 9-4 Cell Populations Involved in Saccadic Control

Cell Population Location Function

Omnipause neurons Distributed throughout midbrainand pons

Exert tonic inhibitory effect on burstneurons to prevent unwanted saccades

Burst neurons Paramedian pontine reticular formation(horizontal), rostral interstitial nucleusof medial longitudinal fasciculus(vertical)

Control ‘‘pulse’’ of innervation to initiatesaccades; project to motor neurons

Motor neurons Abducens nucleus (horizontalmovements), oculomotor and trochlearnuclei (vertical movements)

Project directly to extraocular muscles toinitiate contraction

Interneurons Abducens nucleus (horizontalmovements), oculomotor and trochlearnuclei (vertical movements)

Connect ocular motor nuclei (cranialnerves III, IV, VI) to produce conjugatemovements

KEY POINTS

A Cerebral

control of eye

movements is

contralateral

for saccades

and ipsilateral

for smooth

pursuit.

A 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.




saccades are assessed by asking thepatient to refixate between two targets(such as the examiner’s fingers), usu-ally 308 to 408 apart. Normal refixationmovements should be accomplishedwith one saccade or may undershootthe target and require one or twocatch-up saccades to reach the target.Three or more refixation saccades areconsidered hypometric and abnormal,particularly if asymmetric. Hypermet-ric saccades overshoot the targets andare always abnormal, often indicatingipsilateral cerebellar system dysfunc-tion. Saccadic hypometria indicates ce-rebral dysfunction but is otherwise(in isolation) nonlocalizing. The anti-

saccade task requires that the patientproduce an eye movement in the di-rection opposite a novel visual target(eg, a finger). This task requires thepatient to suppress the natural ten-dency to refixate toward the new tar-get and suggests damage to the frontallobes or the descending projectionsthrough the basal ganglia; this is oftenabnormal in Huntington chorea andother disorders affecting frontal lobefunction.

Smooth Pursuit

Smooth pursuit eye movements areused to track objects moving in the

135

KEY POINTS

A Saccadic

processing is

shared by

several cortical

areas and both

hemispheres,

so unilateral

hemispheric

dysfunction

generally

causes only

minor transient

saccadic deficits.

A Saccades should

be tested for

accuracy and

speed by

having the

patient refixate

between two

targets about

408 apart.

FIGURE 9-3 A schematic diagram demonstrating cortical and subcortical pathways involvedin smooth pursuit. Retinal image motion produces signals passing throughthe lateral geniculate nucleus to the striate cortex, as well as medial superior

temporal visual area (MST), middle temporal visual area (MT), posterior parietal cortex, andthe frontal eye fields (FEFs) and supplementary eye fields (SEFs). These areas project to thecerebellum via the pontine nuclei. These cerebellar areas project to the ocular motor neuronslocated in the ocular motor nuclei (III, IV, VI).

DLPN = dorsolateral pontine nucleus.

Adapted with permission from Leigh RJ, Zee DS. The neurology of eye movements. 3rd ed. New York: OxfordUniversity Press, 1999:165.



environment. The goal of the system isto generate a smooth eye velocity thatmatches the velocity of a visual target.

Visual motion processing drives pur-suit. Smooth pursuit pathways are lesswell understood than saccadic path-ways, but a critical area, based on func-tional neuroimaging and lesion studies,is the junction of the occipital andtemporal lobes, analogous to the me-dial temporal (MT) and medial supe-rior temporal (MST) region in mon-keys. The posterior parietal lobe andboth the SEF and FEF contribute tosmooth pursuit. Axons descend fromthe ipsilateral TPO junction and FEFto the ipsilateral dorsolateral pon-tine nucleus (DLPN). Fibers cross andreach the contralateral cerebellar floc-culus and then project to the vestibularnuclei. The projections cross again andreach the abducens nucleus, ipsilateralto the originating cortical signal. Con-trol of smooth pursuit, in distinction to

saccades, is ipsilateral: the left hemi-sphere is involved in leftward smoothpursuit and vice versa (Figure 9-3).

Smooth pursuit disorders. Whenthe smooth pursuit system cannotkeep up with target movement, themore durable and evolutionarily oldersaccadic system is called on to recap-ture the object of interest. This resultsclinically in saccadic pursuit, in whichan excessive number of small saccadesintrude on pursuit. Since this systemrelies on widespread neural network-ing, it is vulnerable to dysfunction inmultiple areas of the brain. Symmetricloss of pursuit may be caused by abroad range of neurologic disorders,as well as inattention, age, and med-ications, and is, therefore, a nonspe-cific finding (Table 9-5). Asymmetricsmooth pursuit suggests lateralizedneurologic dysfunction, usually cere-bral and ipsilateral to the directionof abnormal pursuit. Such lesions areoften located in the cortex or subcor-tical white matter of lateral occipito-temporal or the dorsomedial frontalregions (Lekwuwa and Barnes, 1996).

Clinical evaluation of smoothpursuit. Smooth pursuit is examinedclinically by having the patient track aslowly moving accommodative target,such as the 20/200 letter on a near card.We can normally smoothly pursue atarget moving at 108 to 408 per second.It is important to move the target at thisrate; rapidly moving a target back andforth will overcome even a normalsmooth pursuit system and give a falseimpression of impaired pursuit.

Vertical Eye Movement Control

Vertical saccades are generated bi-hemispherically, and signals descendto the rostral interstitial nucleus ofthe MLF (riMLF), located at the meso-diencephalic junction. The riMLF con-tains burst cells responsible for verticaland torsional saccades. The riMLF proj-ects to themotor neurons of the elevator

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TABLE 9-5 Causes ofSymmetricallyImpaired SmoothPursuit

" Sedative-HypnoticMedications

" Anticonvulsants

" Brainstem/CerebellarDysfunction

" Toxic-MetabolicEncephalopathies

" Advanced Age

" Inattention

" Fatigue

" Basal Ganglia Disorders

Parkinson disease

Huntington disease

Wilson disease

Progressive supranuclear palsy

KEY POINTS

A Cortical areas

in the medial

temporo-

occipital,

parietal, and

frontal lobes

participate in

the control of

smooth pursuit.

A Symmetrically

abnormal

(saccadic)

smooth pursuit

is a nonspecific

marker of

generalized

cerebral

dysfunction.

Asymmetrically

impaired

smooth pursuit

suggests focal,

ipsilateral,

hemispheric

disease.




(superior rectus, inferior oblique) nu-clei bilaterally, and the depressor (su-perior oblique, inferior rectus) nucleiipsilaterally.

The interstitial nucleus of Cajal(INC) is located in the rostral midbrainand may function as the neural inte-grator for vertical gaze. The INC receivesinput necessary for vertical vestibularand smooth pursuit movements fromthe medulla and pons, largely conveyedby the MLF (Dalezios et al, 1998). TheINC projects via the posterior commis-sure (PC) to motor neurons of cranialnerves III and IV and to the contralat-eral INC (Scudder et al, 2002).

The PC crosses posterior to thethird ventricle at its junction with theaqueduct, rostral to the SC. This path-way conveys crossing fibers of the INCand receives axons from the nucleusof the PC. The nucleus of the PC con-tributes to upgaze generation and co-ordination between eye and eyelid move-ments (Partsalis et al, 1994) (Figure 9-4).

Vestibular-Ocular System

The vestibulo-ocular reflex (VOR) pro-duces conjugate eyemovements that areequal and opposite to head movements.

The VOR keeps gaze (the sum of eyeposition and head position) stable rela-tive to the visual world and ensures thatimages remain stable on the fovea. TheVOR is anatomically and conceptuallydivided into two components: (1) thehorizontal VOR and (2) the vertical andtorsional VOR. The VOR depends ondirect connections between the periph-eral vestibular system (ie, labyrinth andvestibular nerve) and the central ocularmotor system (ie, the ocular motornuclei). The cerebral modulation of theVOR remains poorly understood, al-though recent data from functionalneuroimaging have emerged (Dieterichand Brandt, 2008). Recent evidencesuggests that cortical processing of ves-tibular input is distributed among mul-tiple areas, including the posterior insu-lar cortex and the parietal and frontalcortex.

The horizontal VOR is producedby projections from the horizontalsemicircular canals to the ipsilateral oc-ulomotor nucleus and contralateral ab-ducens nucleus, causing the yoked me-dial and lateral rectimuscles to fire. Thesefibers carry the head and eye veloc-ity commands. The integrated positioncommand is generated by the nucleus

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FIGURE 9-4 Brainstem centers involved in vertical gaze control. The rostral interstitialnucleus of the medial longitudinal fasciculus (riMLF) contains burst neuronsresponsible for initiating upward, downward, and torsional saccades. The

pathways controlling upgaze pass more dorsally in the posterior commissure (PC) and are morevulnerable to lesions in the dorsal midbrain.

INC = interstitial nucleus of Cajal; IO = inferior oblique; SR = superior rectus.

KEY POINT

A 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.



prepositus hypoglossi and the medialvestibular nucleus, and then carried tothe medial and lateral rectus motorneurons (Figure 9-5).

The vertical and torsional VOR aregenerated by projections from the an-terior and posterior semicircular ca-nals to the oblique and vertical rectus

138

FIGURE 9-5 The excitatory connections of the horizontal vestibulo-ocular reflex. Leftwardhead rotation causes endolymph flow in the horizontal semicircular canalsto excite hair cells, which transmit eye velocity commands to the ipsilateral

vestibular nucleus (not shown), then to the contralateral abducens nucleus. Motor neurons in theright abducens nucleus project directly to the right lateral rectus, resulting in abduction of theright 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 isrightward eye movements in response to leftward head rotation (see also Figure 9-2).

KEY POINT

A The integrity of

the vestibulo-

ocular 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.




muscles. Activation of both anteriorcanals by downward head accelerationinduces the upward VOR, while acti-vation of both posterior canals by up-ward head acceleration induces thedownward VOR. Contraction of theipsilateral superior rectus and contra-lateral inferior oblique, in response toactivation of the ipsilateral anteriorcanal, results in elevation and contra-lateral torsion of both eyes. Contrac-tion of the ipsilateral superior obliqueand contralateral inferior rectus, in re-sponse to activation of the posteriorcanal, results in depression and contra-lateral torsion of both eyes. When ver-tical head acceleration activates bothanterior canals, the torsional signals can-cel out, resulting in purely vertical move-ment. Similarly, when head roll or tiltactivates both vertical posterior canals,the vertical signals cancel each other,producing a purely torsional movement(Figure 9-6).

Implicit in the normal functioningVOR is adequate cancellation of theVOR when pursuing an object thatmoves in synchrony with head and eyemovement; without appropriate can-cellation, the VOR moves the eyes inthe direction opposite to the head,then requiring a catch-up saccade toreach the target. Impaired cancellationof the VOR, often associated clinicallywith impaired smooth pursuit, is a sen-sitive but relatively nonspecific localiz-ing sign of cerebral, brainstem, or, mostoften, cerebellar disease.

Clinical evaluation of the vestibulo-ocular reflex. VOR gain (the ratioof eye velocity to head velocity asthe eyes and head move in oppositedirections) must be close to 1.0 tomaintain normal vision and can beassessed in clinic. Abnormal VOR gain(too low or too high) causes images tomove across the retina and resultsin visual blur or apparent motion ofthe environment (oscillopsia). Thedynamic visual acuity test is an easy

method to detect bilateral VOR gainabnormalities; the patient’s head is ro-tated left and right at 2 Hz to 3 Hzwhile attempting to read the Snellenvisual acuity chart. Patients should weartheir usual and appropriate prescrip-tion while this test is performed. If VOR

139

FIGURE 9-6 The vertical vestibulo-ocular reflex isgenerated by endolymph movement in theanterior and posterior semicircular canals

(SCCs). Downward head rotation (top) activates both anteriorSCCs and induces (via connections to the elevation subnucleiof the oculomotor nerve) upward slow eye movements.Upward head rotation (bottom) stimulates both posteriorSCCs and causes (via connections with the depressorsubnuclei of the oculomotor nerve and the trochlear nuclei)downward eye movements.



gain is normal, visual acuity should bethe same as their best corrected visualacuity performed with the head sta-tionary. If Snellen visual acuity falls bytwo or more lines, VOR gain is too lowor too high.

The head impulse test is a moresensitive technique, able to detect uni-lateral or bilateral abnormalities ofVOR gain. For this test, the patientsare asked to fixate on a distant targetwearing their usual and appropriatecorrection. The examiner grasps thepatient’s head and rapidly rotates thehead horizontally, about 208 to 308.The VOR response elicited results fromexcitation of the ipsilateral horizontalsemicircular canal. If VOR gain is nor-mal, the patient’s gaze remains steadilyupon the target. A catch-up saccadeback to the target at the end of the headrotation suggests abnormal VOR gain onthe side of the head thrust.

Imbalance of the VOR induces nys-tagmus. The slow phase of peripheralvestibular nystagmus is enhanced by re-moval of fixation, using either Frenzel(+20 diopter) lenses or by performingophthalmoscopy on one eye while cov-ering the other. Central vestibular nys-tagmus is not influenced by fixation (seethe chapter on nystagmus).

Cerebellar Control ofEye Movements

The cerebellum plays a major role incoordinating and calibrating all eyemovements. The vestibulocerebellum(flocculus, paraflocculus, nodulus, andventral uvula) deals with stabilizationof sight during motion, whereas thedorsal vermis and fastigial nuclei influ-ence voluntary gaze shifting (Table 9-6).

Flocculus and paraflocculus. Thefloccular complex helps generate smoothpursuit and governs the neural integrator

140

KEY POINTS

A 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.

A 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.

TABLE 9-6 Cerebellar Control of Eye Movements

Cerebellar Structure Function Result of Lesion

Flocculus andparaflocculus

Aids in generation ofsmooth pursuit and helpsmaintain eccentric gaze;calibrates step-pulse ratioof saccades

Saccadic smooth pursuit

Gaze-evoked nystagmus

Downbeat nystagmus

Nodulus and uvula Decreases duration ofvestibular responses;inhibits velocity storage

Increased duration ofvestibular responses

Periodic alternatingnystagmus

Fastigial nucleus Accelerates contraversivesaccades; involved incoordination of smoothpursuit

Hypometric contraversivesaccades

Hypermetric ipsiversivesaccades

Dorsal vermis Tonic inhibitory control offastigial nucleus

Hypermetriccontraversive saccades

Hypometric ipsiversivesaccades

Ipsilateral saccadicsmooth pursuit




in maintaining eccentric gaze (Lisbergeret al, 1984). Damage to the floccularcomplex results in saccadic pursuit andimpaired gaze-holding, manifesting asgaze-evoked nystagmus and reboundnystagmus. This complex also calibratesthe pulse–step ratio of saccades and theamplitude of the VOR, adjusting them inresponse to changes in the visual envi-ronment and visual needs.

Nodulus and uvula. The nodulusand the adjacent uvula decrease theduration of vestibular responses throughregulation of the velocity-storage systemin the vestibular nucleus (Choi et al,2007). This system extends the decaytime of head velocity signals receivedfrom the semicircular canals. The netresult is prolongation of the responseof the VOR to a constant head velocityand enhancement of VOR gain at lowaccelerations. Release of the storedvestibular signal is required when itconflicts with information from theafferent visual system or with gravita-tional signals from the utricles. Thenodulus inhibits velocity storage, andnodular lesions (around the roof ofthe fourth ventricle) result in periodicalternating nystagmus.

Doral vermis and fastigial nu-clei. The dorsal vermis and fastigialnuclei play critical roles in saccadiccontrol and have roles in the coordi-nation of smooth pursuit (Catz andThier, 2007). The fastigial nucleus ac-celerates contralateral saccades throughprojections looping around the superiorcerebellar peduncle and terminating atthe contralateral PPRF. Lesions of thefastigial nucleus (or projections) causehypometric contralateral saccades andhypermetric ipsilateral saccades. Sincethe fastigial nucleus is under inhibitorycontrol of the vermis, lesions of thelatter structure result in hypometricipsilateral and hypermetric contralat-eral saccades. Vermal lesions also im-pair smooth pursuit, usually towardthe side of the lesion.

HORIZONTAL GAZE DISORDERS

Horizontal Gaze Palsy

Abducens nucleus lesion. Damageto the abducens nucleus results in anobligate ipsilateral gaze palsy, evidenton examination as an inability to looktoward the side of the lesion. There isan inability to activate the ipsilaterallateral rectus and contralateral medialrectus for all classes of eye move-ments, including vestibulo-ocular. Nu-clear abducens palsies are often ac-companied by an ipsilateral peripheralfacial nerve palsy (due to the proxim-ity of the facial colliculus). The gazepalsy may be asymmetric with theabducting eye more prominently af-fected. This may be due to selectivevulnerability of the motor neuronscompared to interneurons or may re-flect concomitant involvement of theabducens fascicle. The etiology is usu-ally either ischemia or compression/infiltration. (See Case 9-1 with VideoSegment 51 of horizontal gaze palsy.)

Paramedian pontine reticularformation lesion. Lesions of the PPRFcause selective loss of ipsilateral hori-zontal saccades. Acutely, there may be acontralateral gaze deviation (eg, a rightgaze deviation with a left PPRF lesion).In contrast to lesions involving the ab-ducens nucleus, the horizontal oculoce-phalic reflex (doll’s eye) in a PPRF lesionis preserved, since vestibular fibers proj-ect directly to the abducens nucleus.Etiologies are similar to abducens nervepalsy (Figure 9-7).

Cerebral gaze palsy. Acute, uni-lateral hemispheric injury may causetransient gaze palsy or gaze deviation.This most often occurs with parietaland right-sided lesions. The eyes aredeviated ipsilateral to the lesion. Thegaze deviation may be overcome withhorizontal oculocephalics and usuallychanges within days to a gaze prefer-ence, in which the patient can redirectgaze with prompting. This should

141

KEY POINTS

A Lesions of

the floccular

complex result

in saccadic

smooth pursuit,

impaired

cancellation of

the VOR, and

gaze-evoked,

rebound, and

downbeat

nystagmus.

A Lesions of

the nodulus

prolong the

duration of

vestibular

responses and

may cause

periodic

alternating

nystagmus.

A 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.



be distinguished from gaze apraxia,which implies difficulty initiating visuallyguided saccades. Other localizing fea-tures, such as hemineglect, visual fielddefect, and anosognosia are often pres-

ent. The most common causes arestroke and tumor.

Internuclear ophthalmoplegia.Lesions of the MLF may result in im-paired adduction during conjugate gaze

142

FIGURE 9-7 The effect of lesions on horizontal eye movements. A lesion of the rightparamedian pontine reticular formation (PPRF) (1) results in selective loss ofrightward horizontal saccades. The horizontal vestibulo-ocular reflex (VOR) is

spared and vergence movements are preserved. Damage to the right abducens nucleus (2) resultsin 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 maycause a frank adduction defect, or simply slow adducting rightward saccade (‘‘adduction lag’’).

IN = interneurons; MN = motor neurons.

KEY POINT

A 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 9-1A 53-year-old woman presented with a 3-day history of left-sided weaknessand difficulty seeing toward the right with both eyes. Her neurologicand neuro-ophthalmic examinations were significant for a mild lefthemiparesis and a partial right gaze palsy. MRI of the brain showed highT2 signal in the right paramedian pons. Diffusion-weighted imaging wasconsistent with acute ischemic stroke. Video Segment 51 demonstrates herocular motor examination. Note that vertical movements and vergencewere spared. All rightward eye movements were affected, implicatingthe right abducens nucleus rather than the PPRF (see discussion relatingto PPRF). Also note the contralateral gaze-evoked nystagmus with aprominent rebound component.

Comment. Damage to the abducens nucleus results in an ipsilateralobligate gaze paresis for all classes of eye movements. The usual cause isischemic or hemorrhagic stroke, but demyelination, tumor, and vascularmalformation are other potential causes.




contralateral to the lesion: an INO. TheMLF lesion is on the side of thepoor adduction. Dissociated nystagmusof the abducting eye is a common, al-though not invariant, feature and mostlikely reflects central adaptation (Zeeet al, 1987). Subtle INO may manifest asa slowing of adducting saccades com-pared with abducting movements. AnINO can be differentiated from a partialthird nerve palsy by the lack of othersigns of third nerve dysfunction (infe-rior rectus, superior rectus, inferioroblique weakness, ptosis, pupillary sizeand reaction) and the preservation, insome cases, of medial rectus functionduring convergence. Many patients witha unilateral INO do not report diplopiain primary gaze as there is typically onlyminimal misalignment in this position.Bilateral INO may cause a large exotro-pia (eyes turned out) known as wall-eyed bilateral INO (WEBINO), and pa-tients note horizontal diplopia in alldirections of gaze. The etiology of INOvaries with the age of the patient. Inchildren, the most common cause isneoplasm, followed closely by demye-lination. This is reversed in adults, in

whom demyelination predominates. Inolder adults, ischemia is the most fre-quent etiology because the MLF is sup-plied by end arteries (perforating ves-sels from the basilar), and the INO istypically unilateral. (See Case 9-2 withVideo Segment 52 of bilateral INO.)

One-and-a-half syndrome. Lesionsof the ipsilateral abducens nucleus andipsilateral MLF cause loss of all horizon-tal eye movements except for abductionof the contralateral eye. Vertical andvestibular movements are spared, and askew deviation (see later discussion) iscommon. Acutely, the contralateral eyemay deviate outward due to unopposedresting neural activity reaching lateralrectus muscle from the intact abducensnucleus, a syndrome called paralyticpontine exotropia. Associated localizingfeatures, such as facial and trigeminalnerve palsy and contralateral hemiple-gia, may be present. Etiologies includeischemia, demyelination, and tumor.(See Case 9-3 with Video Segment54 of one-and-a-half syndrome.)

Thalamic esotropia and wrong-way deviation. Thalamic lesions (usuallyhemorrhagic) may cause horizontal gaze

143

Case 9-2A 41-year-old man presented to the neuro-ophthalmology clinic witha 1-week history of diplopia. The diplopia began soon after he returnedfrom a trip to Las Vegas and was described as constant, binocular, andassociated with mild gait instability. His neuro-ophthalmic examinationwas notable for mild bilateral adduction defects and abducting nystagmus.Video Segment 52 demonstrates his ocular motor findings. Note that theadduction defect is partial, and he has prominent bilateral adduction lag,the most sensitive sign of INO. MRI of the brain demonstrated an enhancingdemyelinating plaque in the dorsal pons and two periventricular T2 brightsignals, consistent with asymptomatic previous demyelination.

Comment. INO, either unilateral or bilateral, is a common presentingfeature of multiple sclerosis. It is important to note that the adductiondefect may be subtle, and the presence of slowed adducting saccadesconfirms INO as the etiology. The presence of abducting nystagmusis nonspecific and may be seen in ‘‘pseudo-INO’’ due to myastheniagravis. This may reflect central adaptation or an application of Hering law,with increased innervation to both the weak medial rectus and normallateral rectus.

KEY POINT

A 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.



abnormalities. Acute thalamic hemor-rhage may be associated with a con-tralateral gaze deviation (ie, right tha-lamic lesion causing left gaze deviation).This has been called a wrong-way de-viation, since it is opposite what wouldbe seen in a cerebral lesion (Messeand Cucchiara, 2003). The etiologyis unclear but may be related to anirritative focus causing inappropriatestimulation. Thalamic esotropia (alsocalled pseudoabducens palsy) is anesodeviation (eyes turned in) that maybe seen with acute thalamic lesions.The mechanism may be disinhibitionof medial rectus subnucleus neuronsthat function in convergence.

VERTICAL GAZE DISORDERS

Patients with acute or subacute pare-ses of vertical gaze usually have lesionslocated within the midbrain. Since ver-tical gaze shifts are initiated bilaterally,unilateral hemispheric and brainstemlesions cause only minor vertical eyemovement abnormalities. Lesions atdifferent levels of the midbrain may

produce distinct ocular motor deficits(Table 9-7).

144

Case 9-3A 44-year-old woman presented with a 2-day history of diplopia andright-sided numbness. Her medical history was benign, and she had nohistory of previous neurologic events. Her general neurologic examinationwas notable for patchy predominately right-sided hemisensory loss. Herneuro-ophthalmic examination was remarkable for nearly completeophthalmoplegia, with the only surviving eye movement being rightabduction. Video Segment 54 shows the relevant findings. Note the lackof ptosis and the preserved vertical movements. MRI demonstrated alarge ring-enhancing lesion in the left paramedian pons with multiple,predominately periventricular T2 bright signal, compatible with extensivedemyelinating disease.

Comment. One-and-a-half syndrome (one whole gaze palsy andone half of a gaze palsy) results from a lesion in the paramedian pons.This has also been termed paramedian pontine exotropia. All classesof eye movements include an ipsilateral gaze palsy (resulting frominvolvement of the ipsilateral abducens nucleus) and an ipsilateral INO,secondary to damage to the MLF. The only residual intact eye movementtherefore is abduction contralateral to the lesion. Common etiologiesinclude stroke and demyelination.

TABLE 9-7 Localization ofVertical Gaze Palsy

" Paresis of Downgaze

Selective loss of downwardsaccades: bilateral riMLF

Loss of all forms of verticaleye movements: INC or PC

" Paresis of Upgaze

Loss of all forms of verticaleye movements: PC and INC

Convergence-retractionnystagmus with upwardsaccades: PC

" Complete Vertical Gaze Palsy

Selective loss of verticalsaccades: bilateral riMLF

INC or PC

riMLF = rostral interstitial nucleus ofthe medial longitudinal fasciculus;INC = interstitial nucleus of Cajal;PC = posterior commissure.




Bilateral riMLF lesions (eg, infarctionin the territory of the posterior thalamic-subthalamic artery) produce abnormalvertical saccades. Lesions of the INCimpair vertical gaze-holding and may beassociated with torsional nystagmus.

Parinaud syndrome (dorsal mid-brain syndrome) results from dam-age to the PC. Characteristic featuresinclude limitation of upward eye move-ments, tonic sustaineddowngaze (setting-sun sign), and mid-dilated pupils display-ing light-near dissociation (due toinvolvement of the pretectal nuclei)(Keane, 1990). Additional signs includeeyelid retraction in primary gaze (Colliersign) and convergence-retraction nystag-mus with attempted upgaze. The nys-tagmus is best elicited by having thepatient attempt upward saccades (or byhaving the patient watch a downwardlymoving optokinetic nystagmus tape)and appears as a series of repetitive con-vergence movements associated withglobe retraction (Video Segment 56).The most common causes of Parinaudsyndrome are pineal area tumors, mid-brain infarction, hydrocephalus (dueto dilation of the third ventricle andpressure on the dorsal midbrain). Limi-tation of upward gaze with no otherfeatures of Parinaud syndrome is oftenencountered in older adults; this is be-lieved to represent a consequence ofaging, with no lesion detectable.

Bell phenomenon refers to the up-ward and often oblique ocular deviationwith attempted eyelid closure againstresistance. When upward eye move-ments are impaired, the presence of anintact Bell phenomenon, usually asso-ciated with intact vertical VOR, indicatesa supranuclear etiology.

Skew and ocular tilt reaction.Skew deviation is an acquired verticalmisalignment caused by disturbance ofprenuclear vestibular input. Since as-cending vestibular fibers traverse themedulla, pons, and midbrain, skewis often accompanied by other signs

of brainstem dysfunction (such as anINO). Skew may be comitant (ie, a de-viation that is the same amount in alldirections of gaze) or noncomitant.Although the pattern of misalignmentmay resemble a fourth cranial nervepalsy, the direction of torsion helpsdifferentiate between the two disor-ders. With a skew deviation, the highereye is incyclotorted, while in fourthcranial nerve palsy, the higher eyeis excyclotorted. This may be deter-mined either by using a Maddox rodor observing the fundus with a directophthalmoscope and noting the direc-tion of torsion. The hypertropia andexcyclotorsion in skew deviation areoften minimized or absent when thepatient is in the supine position com-pared to an upright position (Parulekaret al, 2008).

The ocular tilt reaction (OTR) con-sists of head tilt, ocular torsion, andskew deviation. The head tilt is towardthe side of the lower ear, and theupper poles of the eyes are rotatedtoward that side as well. OTR reflectsimbalance of otolith inputs and mayrepresent a lesion anywhere from thecontralateral otoliths in the inner earto the ipsilateral INC. Peripheral andlower brainstem lesions cause ipsilat-eral OTR, whereas pontine and mid-brain lesions cause contralateral OTR.Skew and OTR may be seen in a varietyof disorders of the brainstem andcerebellum or as a transient phenom-enon with elevated intracranial pres-sure (Brodsky et al, 2006).

SUPRANUCLEARMOTILITY DISORDERSIN SPECIFIC DISEASES

Neurodegenerative diseases often re-sult in visual dysfunction. The supra-nuclear motility system is selectivelyinvolved in certain conditions, such asParkinson disease (PD) and progressivesupranuclear palsy (PSP). This may in

145

KEY POINT

A 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.



part relate to the influence (usuallyinhibitory) of the basal ganglia on thedescending supranuclear pathways. Insome patients, visual symptoms mayoccur early in the disease course and beone of the presenting features. Carefulassessment of the ocular motor systemcan identify the cause of the visual symp-toms and provide valuable clues whenthe specific diagnosis is in question.

Parkinson Disease

PD is a primary neurodegenerative dis-order characterized pathologically byloss of dopaminergic cells within thesubstantia nigra and clinically by restingtremor, bradykinesia, and rigidity. Theprecise etiology is unknown, and treat-ment is largely symptomatic, most com-monlywith dopaminergic agonists, suchas levodopa.

Visual symptoms are frequently pres-ent in patients with PD but are rarely apresenting feature. Visual hallucinationsoccur in up to 25% of patients with PD;this may occur as a result of dopa-minergic medications or visual corticaldysfunction (Biousse et al, 2004). Othersymptoms may be relatively vague, re-quiring direct and specific questioningto clarify.

Eyelid disorders are common in PD.Decreased blink rate is frequent, re-sulting in dry eye and assorted afferentvisual symptoms. Blepharospasm canoccur as well, possibly due to disinhi-bition of the facial nucleus and sponta-neous firing of orbicularis oculi muscles.Apraxia of eyelid opening occurs lessfrequently; in this condition, the patienthas difficulty initiating opening of theeyelids. Lepore and Duvoisin (1985) re-ported the clinical criteria for the di-agnosis of apraxia of eyelid openingas transitory inability to initiate eyelidopening; no evidence of ongoing orbic-ularis oculi contraction, such as lower-ing of the brows beneath the superiororbital margins (Charcot eyebrow signof blepharospasm), vigorous frontalis

contraction during periods of inabilityto raise eyelids, no oculomotor or ocu-lar sympathetic nerve dysfunction, andno ocular myopathy.

The supranuclear ocular motor sys-tem is affected in PD. Convergence isimpaired in many patients, resultingin convergence insufficiency (CI). In-deed, CI should be a leading consid-eration in PD patients with diplopia.Historical features supporting CI in-clude binocular horizontal diplopia atnear, visual blurring at near after read-ing for a set time period (usually 5 to10 minutes), and relief of symptomswith monocular occlusion. Examina-tion findings confirming CI includereduced convergence amplitudes, re-mote near point of convergence, andexodeviation at near. Correct diagno-sis in the appropriate clinical settingwould obviate the need for extensiveworkup for alternate causes. Treatmentusually involves adequate presbyopic cor-rection and prisms.

The clinical features of most patientspresenting with PD are prolonged sac-cadic latency, hypometric saccades, andimpaired smooth pursuit. Vertical sac-cadic initiation may be more impairedthan horizontal. Saccadic velocity isunaffected or only minimally affected.Smooth pursuit gain is decreased, andcatch-up saccades are frequently ob-served. Increased saccadic intrusions(usually square-wave jerks) are seen inup to 18% of patients with PD; they arerarely symptomatic (PelakandHall, 2004).

Progressive Supranuclear Palsy

PSP, themost commonof the Parkinson-plus neurodegenerative disorders, hasprominent neuro-ophthalmic findings(Steele et al, 1964). Current diagnos-tic criteria include gradually progres-sive disorder, onset at age older than40, either vertical supranuclear palsyor both slowing of vertical saccadesand postural instability with falls in thefirst year of onset. Patients with PSP have

146

KEY POINT

A 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.




parkinsonian features, such as decreasedblink rate, masked facies, axial rigidity,and en bloc turns, and may initially bemistakenly diagnosedwith PD. However,clues to the diagnosis include greateraxial and neck rigidity, marked micro-graphia, frequent spastic dysarthria anddysphonia, lack of resting tremor, eyemovement abnormalities, and minimalresponse to dopaminergic therapy.

As suggested by the name of thecondition, the supranuclear eye move-ment system is often abnormal in PSP.The ocular motor findings are oftenpresent early in the disease course andmay help in differentiating PSP from PDand other causes of parkinsonism.

Saccades in PSP are initially slowed.The classic abnormality is supranu-clear gaze paresis, initially for verticaleye movements but ultimately affect-ing eye movements in all planes. Pa-tients may progress to completeophthalmoplegia. The VOR remains in-tact until late in the disease course.Frequent or continuous square-wavejerks are commonly seen and are morefrequent in PSP than PD. The ratio ofsquare-wave jerks to blink rate mayhelp distinguish PSP from idiopathicPD (Altiparmak et al, 2006).

Eyelid disorders are common in PSP,similar to PD. Decreased blink rate is com-mon and results in dry eyes, occasionally

147

Case 9-4A 72-year-old man presented with a 5-year history of PSP. He had originallydeveloped axial rigidity and gait instability 5 years earlier. He begannoticing frequent contraction of his eyelids 3 years earlier and had beenreceiving botulinum toxin injections for blepharospasm. He also reportedimpaired reading for the past several years. He had to hold readingmaterial up close to his eyes to read effectively. His rigidity had respondedminimally to dopaminergic medications.

Previous evaluation had included neuroimaging, which wasunremarkable, and a variety of blood tests, including antinuclear antibody,serum ceruloplasmin, rapid plasma reagent, erythrocyte sedimentationrate, and liver enzymes, all of which were unremarkable.

Neuro-ophthalmic examination showed best corrected distance visualacuity of 20/25 and near visual acuity of 20/25 OU. Video Segment 55demonstrates salient features of his external and ocular motor examination:he had nearly complete limitation of saccades and smooth pursuit in thehorizontal plane, with complete limitation of saccades and smooth pursuitin the vertical plane. The horizontal limitation was overcome completelywith horizontal oculocephalics, the vertical limitation only incompletelyovercome (not shown in video). He had frequent, bilateral, synchronizedcontraction of orbicularis oculi muscles, consistent with blepharospasm.He had some apraxia of eyelid opening. No measurable convergencewas present. The remainder of his neuro-ophthalmic examination wasunremarkable.

Comment. This patient has advanced PSP. Note the nearly completeophthalmoplegia. His visual symptoms were multifactorial: the readingimpairment was related to the blepharospasm, the inability to look downto read (due to loss of downgaze), and severe convergence insufficiency.He was switched from botulinum toxin type A to type B and was given areading platform to eliminate need for downgaze. He was also referredto a multidisciplinary visual rehabilitation service.

KEY POINT

A 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.



severe. Blepharospasm and apraxia ofeyelid opening may occur as well. (SeeCase 9-4 with video of PSP patient.)

Treatment for the visual symptomsof both PD and PSP are symptomatic.Dry eye should be treated aggressivelywith lubricating drops and ointments,and punctal plugs for refractory pa-tients. Convergence insufficiency canbe treated successfully with base-inprism placed over reading glasses tohelp fusion, although the poor fu-

sional ability of most patients with PSPoften renders prisms less useful. Bot-ulinum toxin is the treatment of choicefor symptomatic blepharospasm and hasbeen used successfully for apraxia ofeyelid opening as well (Jankovic, 1995)Multidisciplinary low-vision services em-ploying optometrists, physical thera-pists, and occupational therapists canbe useful, particularly if associated oph-thalmic conditions (such as age-relatedmacular degeneration) are present.

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