Pontine Goze Center

Although not a discrete anatomic entity, the neurons that function as the
pontine center for horizontal conjugate gaze project directly to the ipsilateral
sixth-nerve nucleus and to the contralateral third-nerve nucleus by way of
the medial longitudinal fasciculus (MLF). Lesions of the abdnucens nucleus
produce a complete paralysis of ipsilateral horizontal conjugate gaze.
involving saccades, pursuit, and vestibular nystagmus. an ipsilateral gaze
palsy. Central isolated sixth-nerve palsies result from lesions of the sixth-
nerve tasciculus and spare the sixth-nerve nucleus. Some lesions (especially
lesions of the PPRF area) also cause an ipsilateral gaze palsy, but may spare
the pursuit or vestibular mechanism. In contrast to the transient deviations
that follow hernispheric lesions. dencits due to lesions of the pontine gaze
center persist for a long period. Other abnormal eye movements. most
associated with pontine lesions and lesions of vestibule-cerebellar function,
are considered in Chapter 14, as are ocular bobbing, upbeat nystagmus. and
downbeat nystagmus.

Medial Longitudinal Fasciculus (lnternuclear Ophthalmoplegio)

Lesions of the medial longitudinal fasciculus (MLF; Table 12-3) between the
third and sixth nerve nuclei produce the clinical picture termed internuclear
ophthalmoplegia (INO). The typical MLF syndrome

TABLE 12-3. CAUSES OF INTERNUCLEAR OPHTHALMOPLEGIA

Multiple sclerosis (commonly bilateral); postirradiation demyelination

Brainstem infarction (commonly unilateral)

Brainstem and fourth ventricular tumor

Arnold-Chiari malformation and associoted syringobulbia

Infection; viral or other forms of encephalitis

Wernickes encephalopethy

Mass effect (eg, subdural hematoma)

Metabolic disorders (eg, hepatic encephalopethy and maple

Syrup, urine disease)

Drug intoxicotions (eg from phenothiozines ond tricyclic antide pressants]

Head trauma

Degenerative conditions; progressive supranuclear palsy Syphilis.

Pseudo-internuclear ophthalmoplegia of myasthenia gravis and

Fisher syndrome

From Leigh RJ, Zee DS. The Neurology of Eye Movements. Philadelphia;

Davis, 1983

consists of an apparent medial rectus paresis in the eye on the side of the
lesion, nystagmus of the abducting eye on lateral gaze to the side opposite
the lesion, and normal medial rectus activity on convergence. The anterior
INO of Cogan, in which convergence is also absent, probably is found only in
larger lesions, possibly with third-nerve nucleus involvement.

The MLF syndrome is a typical supranuclear disorder, because the

apparently paretic muscle is able to produce normal convergence and there
is no diplopia (no heterotropia) in the primary position. A

Figure 12-5. One-and-a-half syndrome in a 19-year-old patient with o

brainstem glioma. (From Sanders EACM: Syndromes of the medial
longitudinal fasciculus, In; Sanders EACM, et al, eds. Eye Movement
Disorders. Hingham, MA; Kluwer, 1987;11; wifh permission).

MLF lesion produces disconjugate eye movements and diplopia on lateral

gaze, because impulses to the lateral rectus travel normally, whereas those
to the medial rectus are interrupted. ln mild degrees of INO, the abducting
nystagmus may be made more obvious by eliciting asymmetric convergence
or by producing fast movements in the direction of the abducting nystagmus.
That is, when there is a right MLF lesion, the abducting nystagmus in the left
eye on left lateral gaze is augmented by optokinetic or vestibular nystagmus
with fast phases to the left.

Combined PPRF and MLF lesions cause striking motility disorders. If the
PPRF and MLF are damaged, there is an ipsilateral gaze palsy and medial
rectus palsy. As a result, the ipsilateral eye can make no horizontal
movements and the contralateral eye can abduct only-the "one-and-a-half
syndrome" (Fig. 12-5]. Acutely, the deviation due to the gaze palsy may
cause the contralateral eye to be exotropic (the ipsilateral eye cant follow
because of its internuclear medial rectus paresis), causing a paralytic pontine
exotropia (PPEX; Fig. 12-6]. Skew deviation occurs frequently with lesions
of the MLF, especially when unilateral, but may occur in many brain-stem
lesions. Usually the higher eye is on the side of the lesion. A skew deviation
is thought to represent an interruption of otolithic inputs.

Cerebellum

The detailed cerebellar control of eye movements is not well understood.

However, the cerebellum is important in the precise control of eye
movements and of saccades in particular. It probably integrates eye
movements, as it does limb movements, in order to provide smooth,
effective control of movement and compensation for ocular motor
abnormalities. information flowing into the cerebellum is integrated and
organized. The resulting output is either directly to the spinal cord or to the
cerebral cortex via the thalamic nuclei. With reference to the ocular motor
sys-tem, it is of interest that the cerebellum has direct input to the ocular
motor nuclei; some of its outflow fibers travel to these nuclei without
synapse, in contrast, direct fibers from the cerebral cortex to the ocular
motor nuclei have never been found, and the exact number of synapses
between the cerebral cortex and the ocular motor nuclei remains unknown,
Certainly, a direct connection of the cerebellum with the ocular motor nuclei
would be of great value for precise ongoing control of eye movement. In
current thinking, the cerebellum provides continuous ongoing correction of
eye movements, "incessantly subject to revision by the continuous feedback
of information to the cerebellum with the further integration in its output and
so on continuously throughout all postures and movements (Ec-cles)

The cerebellum and its projections include premotor areas in which

afferent information (visual, vestibular) projects to the neurons involved in
eye movement. The cerebellum adaptively regulates eye movement with
respect to the environment and re-

Figure 12-6. Top. Oculomotor findings. Right eye is completely immobile in

the horizontal plane. Left eye is moderately exotropic during forward gaze.
adduction to the midline is achieved; with attempted left gaze, further
abduction occurs. Bottom. Histopathologic findings. A. Cross section at level
of mesencephalon. midline thirdnerve nuclei, ventrally exiting nenres are
intact. (SIits in tissue are processing artifacts.) (2.5 x ). B. Cross section at
level of upper pons. Destruction of median tegmentum [arrow] to right of
midline (ie. in region of ll/ILF ana PPRF) as well as necrosis of the basis pontis
is present. The left PPRF and MLP are intact (2.5 x ). C. Mognlfied view of B.
Asterisk represents midline. The Iefl PPRF and MLF are intact. Ischemic
necrosis of the right MLF and PPRF is seen (10 x ), (From Newman NM, Day
SH, Aguilar MJL . Paralyfic ponfine exafropia: A case report with
clinicopafhologic confirmafion. in Komrnereli G, ed. Disorders of Ocular
motility. Neurophysiological and Clinical Aspects. Munich, Germany: JF
Bergman, 1978, with permission.)
 pairs abnormal eye movement production. It controls sacoadic amplitude
and repairs saccadic dysmetria via the verinis and fastigial nuclei; it also
works to stabilize the retinal image (via the flocculus, which appears to aot
as part of the neural integrator) and repairs mismatches of eye, head, and
target movement via the VOR (nodulus).

Cerebellar pathway lesions result in a spectacular group of oculomotor

disorders: dysmetria, flutter, opsoclonus, and other abnormal oscillations.
Most are conjugate disturbances and predominantly disturbances of fast eye
movements [see Chapter 14].

Two other disorders of eye movement involving cerebellar pathways have

been described. One group of patients with cerebellar degenerations has no
normal pursuit movements, only saccadic pursuit. Families with
heredofamiliar spinocerebellar degeneration show a spectrum of slowed eye
movements, including slowed or absent saccades and pursuit. Many intrinsic
"pure" cerebellar degenerations are associated with several less common
types of nystag- mus and other abnormal eye movements of unex-plained
mechanism [Table 12.-4].

Medulla

Three forms of unusual eye movements are frequently correlated with

medullary lesions: [1] downbeat nystagmus; [2] dissociated nystagmus, in
which one eye moves vertically and the other horizontally; and [3) periodic
alternating nystagmus. These abnormal eye movements are of infrequent
occurrence and are very difficult to explain by what is known of ocular motor
pathways and control mechanisms. Spontaneous nystagmus to the
contralateral side and lateropulsion of saccades occur in Wallenbergs lateral
medullary syndrome.

TABLE 12-4. OCULAR MOTOR ABHORMALITIES IN "PI.lRE"

CEREBELLAR DEGENERATIONS

1. inaccurate (dysmetrio) saccades; normal velocities and

latencies

2. Fixation abnormalities: square wave jerks (saccadic intrusions) and

increased slow

drift

3. Impaired smooth pursuit with head still or moving [VOR cancellation];

impaired OKN;
 impaired fixation suppression of caloric-induced nystagmus

4. Postsaccadic drift (glissades)

5. Gaze-evoked nystagmus (occasionally centripetal nystag-

mus)

6. Rebound nystagmus

7. Downbeat nystagmus

8. Positional nystagmus

9. Increased VOR gain

10. Alternating hyperdeviation on lateral gaze [skew]

From Leigh RJ. Zee DS. The Neurology of Eye Movements. Philadelphia:

Davis, 1983.

TABLE 12-5. SOME DRUGS AND TOXIHS THAT AFFECT

EYE MOVEMENTS

Drug or Toxin Reported Effects

Diazepam Reduces soccadic peak velocity.

impairs smooth persuit and gaze
holding. Decreases VOR amplitude.

Tricyclic antidepressants lnternuclear ophthalmoplegia. Total

gaze paresis.

Phenytoin Impaired smooth pursuit and gaze

holding. Downbeat nystagmus,
periodic alter nating nystogmus.
Total gaze paresis.

Phenobarbital and other Impaired smooth pursuit and

barbiturates biturates gaze holding. impaired
vergence. Total gaze poresis.
Decreased accommodative
convergence accommodation ratio.

Carbamazepine Ophtholmoplegia. oculogyric

crises, downbeat nystogmus.

Phenothiozines Oculogyric crises. lnternuclear

ophthalmoplegia.
Methadone Soccodic hypometrio. impairs
smooth pursuit.
Alcohol and marijuana Impaired smooth pursuit and gaze
holding. Alcohol may cause
positionally induced
nystogmus.

Chloral hydrate Impaired smooth pursuit.

Amphelamine Increased accommodative
convergence-accommodation ratio
Chlordecone. lithium, and thdllium Opsoclohus.

Botulinum toxin Ophthalmoparesis.

One-and-a-Half. ln these cases there is a conjugate gaze palsy to one side

("one") and impaired adduction on looking to the other side ("and a half")
[614,829]. As a result, the only horizontal moveignent remaining is abduction
of one eye, which exhibits nystagmus in abduction. Vertical movements and
convergence are spared. The lesion responsible for his condition involves the
PPRF or abdicens nutleus and the adjacent MLP on the side of the complete
gaze palsy. A clinical distinction can be made between the horizontal gaze
palsy in lesfons affecting the rostral part of the PPRF_and those at me level
of the abducens nucleus [193]. When all rapid eye movements (saceades
and quick phases of nystagmus) ipsilateral to the lesion are abolished with
preserved ipsilateral vestibulo-ocular response, the rostral part of the PPRF is
involved (dissociated ipsilateral horizontal conjugate gaze palsy). In contrast.
lesions at the lower pontine level, affecting the PPRF and/or abducens
nucleus, are associated with an ipsilateral horizontal gaze palsy and loss of
reflex vestibular eye movements (dissociated ipsilateral horizontal gaze
palsy) [193].

Patients with the one-and-a-Half syndrome often have XT of the eye opposite
the side of the lesion (paralytic pontine XT) because the eyes tend to drift to
the side opposite the lesion due to the gaze palsy, but adduction in this
direction is limited by, the MLP lesion [709].

Rarely, a primary position ET may occur with the one-and-a-half syndrome,

likely due to involvement of- the abducens nerve fascicle superimposed upon
a lesion of the PPRF and MLP [829]. The one-and-a-half syndrome may be
associated with ocular bobbing [246] and, more often, facial nerve palsy [the
eight-and-a-half syndrome) [218]. Patients with one-and-a-half syndrome
and facial nerve palsies may develop oculopalatal myoclonus weeks to years
after the onset of the ocular motility problem [845,863].

The one-and-a-half syndrome has also been described with facial diplegia
(the "15 1/2 syndrome"[1 1/2 + 7+7 = 15 1/2]) [43]. It may also be
associated with supranuclear facial weakness on the same side as the gaze
palsy and internuclear ophthalmoplegia with lesions of the paramedian
aspect of the dorsal pontine tegmentum, providing evidence for the
existence of corticofugal fibers that extend to the facial nucleus in the dorsal
paraniedian pontine tegmentum [20].

The one-and-a-half syndrome is most often. caused by multiple

sclerosis, infarcts, hemorrhages, trauma, basilar artery aneurysms,
brainstem arteriovenous malformations, and tumors [425,590,829]. A
pseudo on-and-a-half syndrome may be caused by myasthenia gravis
[55,184] and the Miller-Fisher syndrome [59]. A, somewhat similar syndrome
may result fron. two separate lesions involving both MLFS and the roots of
the abducens nerve on the side of the unilateral horizontal "gaze" palsy.
However, in this case, if the "gaze" palsy is incomplete, the eyes would move
tiisconjugately in the direction of the gaze palsy [614]. A true gaze palsy due
to unilateral PPRF damage causes concomitant paresis of both eyes. Also,.a
unilateral ING may be associated with an ipsilateral abducens nerve palsy
(lascicular involvement) without abducens nuclear or PPRF damage (i.e., no
associated gaze palsy. Another type of one-and-a-half syndrome has been
described with rostrai brainstem infarction.

The patient developed a left ptosis, iight conjugate gaze palsy. and
abduction paralysis of left eye cu attempted gaze to left with adduetion
nystagmus of right eye. The horizontal eye movement disorder was similar to
one-and-a-half syndrome except for an abduction paralysis and adduction
nystagmus. TDC left ptosis BHG adduction paralysis were attributed to a left
oculomotor fascicular involvement, while the tight-sided ET and abduction
paresis were consistent with pseudoabducens palsy. Left abduction paralysis
with adduction nystagmus on the right side on attempted gaze to left was
thought to be due- to involvement of the paraiMLF path on the left side and
is called inrgzmuclear opfztltalmoplegia in abduction. [143] A different one-
anda-half syndrome has been described in a patient with mucormycosis of
the cavernous sinus [141]. The patient had an ipsilateral sixth nerve palsy
due to cavernous sinus involvement and ia contralateral horizontal gaze
palsy due to simultaneous carotid artery occlusion with infarction of the
frontal lobe. Contrary to the pontine one-and-a-half syndrome, in which
abduction in one eye is the preserved horizontal movement, this patient had
only preserved adduction in one eye (contralateral to the sixth nerve palsy)
[141].

Vertical Dysconjugate Gaze Palsies

Monoctrlar elevation prrresis ("double-elevator palsy") may occur with

pretectal suprauuclear lesions contralateral to Lhe paretic eye or ipsilateral
to the paretic eye that interrtlpi efferents from the rostral interstitialnucleus
of the MLF to the SR and IO subnuclei (often Bells phenomenon is intact)
[350,767]; Double elevator palsy may cerebellar infarct can, therefore,
present with im- balance as the only neurologic symptom and with conjugate
ocular torsion as the only specihc neurologic sign [536,555].

Skew deviation associated with concomitant ocular torsion and tilts of

the SVV toward the under most eye is a sensitive brainstem sign of localizing
and lateralizing value. The topographic diagnosis of vestibular syndromes in
the roll plane may be summarized as follows [106,107]:

1. The fundamental pattem of eye-head tilt in roll, either complete OTR

or skew. torsion with-out head tilt, indicates a unilateral peripheral
deficit of otolith input or a unilateral lesion of graviceptive brainstem
pathways from- the V N (crossing midline at lower pontine level) to the
INC iu the rostral midbrain.
 2. Skew deviation and tilts of the perceived visual vertical occur with
peripheral or central vestibular lesions from the labyrinth to the visual
cortex and represent the most sensitive sign of vestibular tone
imbalance in roll.

3. All tilt effects, perceptual, ocular motor, and postural, are ipsiversive
(ipsilateral eye lowermost) with unilateral peripheral or
pontomedullasy lesions below the crossing of the graviceptive
pathways. They indicate involvement of medial and for superior VN,
mainly supplied by the vertebral .

4. All tilt effects in unilateral pontomesenceplhalic brainsteln lesions ate

contraversive (contralateral eye loweiniost) and indicate involvement
of the MILF tparaniedioii arteries arising from the basilar artery) or INC
and riMLF (para-median superior mesencephalic arteries arising from
the basilar artery).

5. Unilateral lesions of vestibtlar structures rostral to the INC typically

manifest with deviations of perceived vertical witliont concurrent eye-
head tilt.

6. CTR in unilateral paramedia in thalamic infarction (paramedian

thalarnic an aries from basilar artery) indicates simultaneou: ischemia
of the paramedian rostral midbrain including the INC.

7. Unilateral lesions of the posterolateral thala-mus can cause thaiamic

astasia and moderate i psiversive or contraversive skew deviation
andtilts cf the perceived visual vertical, tliareby indicating involvement
of the vestibular thalamic subnuclci (thalamogeniculate arteries).

8. Unilateral lesions ofthe parietoinsular vestibular cortex cause

moderate, mostly contraversive skew deviation and tilts ofthe
perceived visual vettical (temporal branches off the middle cerebral
artery or deep perxbrators)

9. A skew deviation and tilts of the perceived visual vertical found with
monocular but not with binocular viewing is typical of a trochlear or
oculomotor palsy rather than a supranuclear graviceptive brainstem
lesion.

Infarction in the distribution of the middle cerebial artery, especially affecting

the posterior insula, may cause contraversive, pathologic SVV tilts [109]. The
parietoinsular vestibular cortex therefore likely represents the integration
center of the multisensory vestibular cortex areas within the parietal lobe.
Clinical Classification of Nystagmus

In assessing a patient with abnormal eye oscillations, it is first useful to note

whether the oscillations are confined to one eye (monocular), involve mainly
one eye (binocular asymmetric or dissociated), or involve both eyes
symmetrically (binocular symmetric) [128].

Monocular Eye Oscillations and Asymmetric Binocular Eye

Oscilltions

Monocular eye oscillations and asymmetric binocular eye oscillations may be

due to spasmus nutans and its ntimickcrs, monocular A visual deprivation or
loss, monccular pendular nystagmus, intemuciear ophthalmoplegia and its
mimickers, partial paresis of extraocular muscles, restrictive syndromes of
extraocular muscles, or SOM.

Spasmus nurans is a benign syndrome characterized by a triad of head

nodding, nystagmus, and abnormal head posture [296-353]. This condition
usually has its onset in the Hrst year of life and remits spontaneously within
one month to several years (up to 8 years) of onset. The sinusoidal
nystagmus is cften_intermittcnt, asymmetric or unilateral. and of high
frequency and small amplitude with a "shirnmering" quality. The nysiagnius is
usually horizontal. but may have a vertical or torsional component. The
irregular head nodding with spasmus nutans has horizontal, vertical, or
mixed components.

Patients uiten also demonstrate a head tum or tilt. In all children with
spasmus nutans, monocular nystagmus, or asymmetric pendular nystagmus,
one must consider that the nystagmus may be due to tumor of the optic
nerve, chiasm, third ventricle, or thalamus [26,229,574,726]. These latter
patients may also have visual loss, optic atrophy, or other signs of tumor
[435] A myopic child suspected of having spasmus nutans should also
undergo electroretinographit. testing to exclude the diagnosis of Congenital
stationary night blindness [456]. Monocular nystagmus may occur in adults
or children with acquired monocular visual loss and consists of small, slow
vertical ncntluiai oscillations in the primary posilzoiiol city, It may develop
years after uniocular visual loss (Heimann-Bielschowsky phenomenon) and
may improve if vision is corrected [630,726,857]. Monocular, small
amplitude, fast frequency, and predominantly horizontal nystagmus in
children may be caused by unilateral anterior visual pathway disease [294].

Epileptic monocular horizontal nystagmus has been described in a

cognitively intact adult with normal vision [298]. Focal seizures originated in
the occipital lobe contralateral to the involved eye, and an associated
structural lesion was thought to represent a forme frusta of the Sturge-Weber
syndrome. It was hypothesized that the seizure discharge either activated a
cortical saccade region and caused simultaneous supranuclear inhibition of
ipsilateral eye movement or triggered monocular eye movement commands.

Acquired monocular pendular nystagmus may also occur with multiple

sclerosis, neurosyphilis, and brainstem infarct (thalamus and uppermid-brain)
and may be vertical, horizontal, or multi veetorial [630]. Monocular DBN may
occur with acute infarction of the medial thalamus and upper midbrain and
with pontomrebellar degeneration; this abnormality is likely due to
dysfunction of the ipsilateral brachium conjunctivum [93,574]. Contralateral
unilateral DBN has been described with a paramedien thalamopeduncular
infarction [595]. Monocttlai rotatory nystagmcts may occur with brainstem
lesions [400]. One patient has been described who dcveloped ictal monocuiai
horizontal nystagmtrs during a generalized seizure triggered by photic
stimulation [375].

Nystagmus is seen only in the abduct eye in INO and in pseudo INO
syndromes (see preceding text). SOM (deseribed earlier) may also cause
vertical dscillopsia, vertical or torsional diplopia, or both.

Horizontal Dysconjugate Eye

Oscillations Convergence may evoke various forms of nystagmus (i.e.,

convergence evolced nystagmus-see subsequent text). Convergence-
retraction nysmgmus is a disorder of ocular motility in which repetitive
aclducting saccacles, which are often accompanied by retraction of the eyes
into the orbit, occur spontaneously or on attempted upgaze [600]. Sliding an
optokinetic tape downwarcl in front of the patients eyes may also elicit
convergence-retraction nystaginus. Convergence-reteraction nystagmus is
primarily a saccadic disorder as the convergence movements are not normal
vergence movements but asynchronous, adducting saccades.
Mesencephalic lesions affecting the pretectal region are most likely to cause
this type of nystagmus that is often associated with abnormalities of vertical
gaze. The localization- of these venical gaze abnormalities and convergence-
retraction nystagmus was discussed in the preceding text. Occasionally,
periodic lateralized epileptiform discharges (PLEDS) during
electroencephalography have been found to occur in synchrony with
retraction nystagmus [860]. Convergence nystagmus has been described
without vertical gaze abnormalities in patients with dorsal midbrain stroke
and-in patients with Arnold-Chiari malformation [554,697].

Whipples disease may also cause convergence nystagmus at approximately

one Hz (penduiar vergence oscillations) [703]. Convergence nystagmus has
been described in a patient with spasmus nutans [515].
Divergence nysmgmus (with divergent quick phases) may occur with
hindbrain abnormalities (eg., Chiari inalformation). and is associated with
DBN [857]. These patients have slow phases directed upward and inward.
Repetitive divesggetzce consists of a slow divergent movement followed by a
rapid return tothe primary posidon at regular intervals [580]. This rare
disorder has been described with coma from hepatic encephalopathy. A
similar disorder, probably related to seizures, was reported in a neonate in
association with bursbsuppression patterns of the electroencephalogram
[572].

Oculomasticalory myorhyte refers to acquired penciular vergence

oscillations of the eyes associated with concurrent contraction of the
masticatoiy muscles [6,338,503,701]. When the myorhythmia also involves
nonfacial skeletal muscles, it is called oculo facial-skeletal myorhythmia..

There is a smooth, rhythmic eye convergence, which cycles at a frequency of

approximately 1 Hz followed by divergence back to the primary position.
Rhythmic elevation and depression of the mandible is synchronous with the
ocular oscillations that persist in sleep and are unaltered by stimuli. The
masticatory involvement may occasionally consist of a permanent brurism
leading to severe tooth abrasions [787]. Patients with oculomasticatory
myorliythmia may also have paralysis of venical gaze, progressive
somnolence and intellectual deterioration. This distinct movement disorder
has been recognized only in Whipples disease. Whipple`s disease may also
cause convergence nyslagmus at approximately 1 Hz (pendularvergence
oscillations) [703]