Supranuclear, Nuclear & Infranuclear
Running head: SUPRANUCLEAR, NUCLEAR AND INFRANUCLEAR CONTROL
SUPRANUCLEA
Supranuclear, Nuclear and Infranuclear
Control of Eye Movement and their Disorders YE
MOVEMENT AND THEIR DISORDERS
Hanoof Al-Kharashi
ID # 425200399
OPTO 493
Optometry Department
1
Supranuclear, Nuclear & Infranuclear
Supranuclear Control and Disorder
A number of systems are responsible for producing eye movements and controlling fast (saccades),
slow (smooth pursuit), disjugate (vergence) and involuntary (vestibular) movements. The eye movement
system used depends on the nature of the visual input received and the response required for the visual
stimulus. Visual information reaches the visual striate cortex (primary visual area 17, V1) via the visual
pathway and attributes of this visual information such as fine features, color, spatial localization and
motion are processed in separate secondary visual areas (Rowe, 2003).
Saccades
There is an anatomical separation of horizontal (pontine) and vertical (mesencephalic) premotor
saccadic centers. Although pause cells for both are located in the nucleus raphe interpositus (between the
fascicles of the abducens nerve in the caudal portion of the pontine reticular formation), segregation of the
premotor structures is otherwise virtually complete.
Horizontal
Horizontal excitatory burst cells (EBN), which discharge preferentially for ipsilaterally directed
saccades, are located in the paramedian pontine reticular formation (PPRF). The Output from these cells is
directed to two types of neurones that form the abducens nucleus, motor neurones that are directed to the
ipsilateral lateral rectus and Interneurones which decussate at the level of the abducens nucleus and ascend
in the contralateral median longitudinal fasciculus (MLF) to terminate in the contralateral medial rectus
subnuclei in the mesencephalon. Neural integration occurs within the medial vestibular nucleus and the
adjacent nucleus prepositus hypoglossi (Acheson & Riordan-Eva, 1999).
So, Horizontal saccades are controlled by contralateral frontal eye fields in the frontal lobe. The right
frontal lobe controls saccades to the left, and the left frontal lobe controls horizontal saccades to the right.
Vertical
Vertical EBN are located in the rostral interstitial nucleus of the MLF (riMLF). This nucleus lies at
the mesodiencephalic junction dorsal to the red nucleus. Cells on each side discharge for both upward and
downward directed saccades but discharge preferentially for torsional movements directed ipsilaterally (ie
extortion of the ipsilateral eye and intorsion of the contralateral eye). The output for upward saccades
decussates through the posterior commissure whereas the output for downward saccades runs ventrally to
the ipsilateral trochlear and inferior rectus subnuclei. The site of the neural integrator for vertical eye
movements in man is not yet fully established but it probably resides in the interstitial nucleus of Cajal
(INC) in the rostral mesencephelon. For both horizontal and vertical eye movements the cerebellum is
2
Supranuclear, Nuclear & Infranuclear
involved in integrating the output of the burst cells. The output from the cerebellum enters the brain stem at
the level of the vestibular nuclei and for vertical movements it then ascends to the IN C via the MLF.
Cortical
Cortical control of saccades is also segregated largely between two cortical areas: frontal and
parietal. Both have a direct input into the brain stem via the superior colliculus and the frontal cortex
additionally relays through the basal ganglia in what appears to be an inhibitory circuit. Frontally driven
saccades are volitional whereas parietally driven saccades are reflexive (Acheson & Riordan-Eva, 1999).
Fig. 1
3
Supranuclear, Nuclear & Infranuclear
Disorders of saccades
Such disorders can be produced by lesions anywhere from the frontal lobe to the paramedian
pontine reticular formation (Steiner & Melamed 1984; Kernan et al. 1993; Shawkat et al. 1996).
A lesion in the region of the burst cells will result in a gaze palsy, as no pulse will be generated.
Lesions to the neural integrator result in gaze evoked nystagmus, as it is not possible to overcome the
orbital elastic forces (the more severe the lesion the more rapid the slow decay of eye position back to the
primary position). Lesions outside the main nuclei (i.e. the cerebellum) result in saccadic dysmetria due to
a mismatch between the pulse and step. Lesions in the region of the pause cells will result in opsoc1onus
(back to back saccades) if inhibitory tone is lost, or slowed saccades if coherent switching is lost (ie the
cells switching off the pause cells do not fire in concert). Failure to generate saccades to command is
termed ocular rnotor apraxia: children with developmental delay syndromes may demonstrate abnormal
visual behavior with characteristic head thrusts to refixate the eyes because of a congenital form of this
disorder (Acheson & Riordan-Eva, 1999, P.154).
Disorders of saccades result in abnormalities of initiation, velocity, accuracy and inappropriate
saccadic intrusions. Saccadic disorders can be classified according to whether the pulse, step or the pulsestep match is inappropriate. For example, hypometric saccades relate to a deficient pulse-step signal.
Where burst neurons activate too much (excessive pulse) with a normal response from inhibitory neurons
(normal step), an overshoot of the target results which then requires a drift of the eyes (glissade) back to the
target. Dysfunction of specific cell types within the brainstem reticular formation may account for various
types of saccadic disorders. Slow saccades may be noted with nerve palsies or drug use. Accuracy
disorders may be noted with brainstem or cerebellar disease. Disturbance of saccadic initiation with
prolonged latencies and inaccuracy can be seen in degenerative and demyelinating conditions such as
Huntington' s chorea and multiple sclerosis (Rowe, 2003).
Unilateral saccadic deficit
There is loss of voluntary movement to the contralateral side. Binocular single vision is normally
maintained in the primary position but diplopia is not commonly appreciated, even looking to the affected
side, as the defect is conjugate. Doll's head movement is usually intact. An object may be followed slowly
if foveal fixation is maintained into the affected field. Gaze paretic nystagmus may be seen to the affected
side (jerky nystagmus with fast phase to the opposite side of the lesion).There may be facial and/or upper
limb paralysis on the ipsilateral side. Destructive unilateral lesions result in a unilateral contralateral
saccadic deficit which may be due to vascular or space occupying lesions or trauma. Vascular lesions are
most common such as an acute cerebrovascular accident (Rowe, 2004, P.298).
4
Supranuclear, Nuclear & Infranuclear
Bilateral saccadic deficit
There is a complete saccadic palsy with absent horizontal and vertical saccades and no voluntary
rnovernent. Bilateral cortical lesions, which may result in a complete saccadic palsy, are often associated
with decreased levels of consciousness (Rowe, 2004).
Ocular motor apraxia
This is a congenital condition in which there is an inability to make voluntary horizontal saccades
when the head is irnmobilised. The patient rnakes use of head thrusts to induce compensatory movements
of the vestibular system. Typically the eye lids are closed at the onset of the head movement in order to
help break fixation. The head is thrust in the direction of and past the position of the target to be fixated.
Due to the vestibulo-ocular reflex, the eyes deviate in the opposite direction. The head is moved until the
eyes come in line with the target to be fixated. Once fixation is obtained, the head is moved back to a
straight position, making use of the normal smooth pursuit movements to maintain fixation on the target.
The thrusts become less apparent with age (Rowe 1995; Harris et al. 1996).
The condition may also be acquired, e.g. secondary to inflammation and with extensive bilateral
cerebral disease. Balint's syndrome is an acquired condition of saccadic palsy. There may be impaired
reading and simultanagnosia which is an inability to perceive more than one object at a time (Rowe, 2004).
Huntington’s chorea
This is an autosomal dominant defect with insidious onset, usually from 30 years onwards. Marked
loss of saccadic velocity is noted and the patients develop dysarthria and choreic movements (most
noticeable in the face and distal extremities). There is progressive mental deterioration in later stages
(Rowe, 2004, P.299).
Dementia
This is abnormal fixation with saccadic interruptions. Increased latency, hypometria and slowing of
saccades are noted. Vertical saccades are affected more than horizontal saccades. There may be
abnormalities of smooth pursuits with decreased gain. Saccadic deficits are due to frontal lobe dysfunction
but there may also be some parietal lobe involvement. Conditions such as Alzheimer's disease may exhibit
the above (Rowe, 2004, P.299).
Multiple sclerosis
As a result of demyelination of nerve fibres large saccades may show velocity changes such as
increased latency and inaccuracy. Smooth pursuit gain can be decreased. Other ocular motility disorders
may be recorded including VI nerve palsy, INO and gaze palsies (Rowe, 2004, P.299).
Pseudoabducens palsy
During horizontal saccades, the abducting eye may move more slowly and may reflect an excess of
convergence tone. This is a nearly symptom of posterior commissure lesions such as pineal tumours,
5
Supranuclear, Nuclear & Infranuclear
hydrocephalus, vascular lesions, metabolic disorders and MS. Reading difficulties are caused by poor
tracking and focus (Rowe, 2004).
Smooth Pursuit
As there is no need for a ballistic movement, the signal to the brain stem bypasses the burst cells,
and feeds into the contralateral cerebellar flocullus, vermis, and uvula, via the ipsilateral dorsolateral
pontine nuclei. The dorsolateral pontine nuclei (subadjacent to the abducens nuclei) receive their input
from MST and from the frontal eye fields (which in turn receive output from area MT). The output from
the cerebellar centres again crosses the midline to terminate in the ipsilateral vestibular nuclei. The output
from the vestibular nuclei is then passed to the ocular motor nuclei (Acheson & Riordan-Eva, 1999, P.151).
So, pursuit movements are controlled by the ipsilateral parietal lobe (ie, right pursuit is driven by the right
parietal lobe, and left pursuit is driven by the left parietal lobe).
Fig. 2
6
Supranuclear, Nuclear & Infranuclear
Disorders of smooth pursuit
Smooth pursuit disorders are caused by lesions involving the occipitoparietal lobe and pathways to
the paramedian pontine reticular formation (Leigh & Tusa 1985; Lekwuwa & Barnes 1996; Morrow
&Sharpe 1995).Normal smooth pursuit movements are replaced by series of small saccades termed 'cog
wheeling' (Rowe, 2003.P.300).
A lesion in the motion sensitive cortex (MT) will result in defective initiation of smooth pursuit in
this area of visual field. A lesion in the adjacent area (MST) will result in a deficit of smooth pursuit in the
contralateral hemifield. A lesion in the cerebellum will result in low pursuit gain with catch-up saccades broken pursuit (Acheson & Riordan-Eva, 1999).
Unilateral smooth pursuit deficit
Unilateral disorders are most often caused by lesions in the posterior cortical hemisphere or in the
hemisphere of the cerebellum. Cortical lesions produce loss of smooth pursuit to the ipsilateral side. This is
accompanied by Cogan's sign and the patient may also have homonymous contralateral visual field defects.
Hemisphere lesions produce ipsilateral smooth pursuit defects without producing the other signs found in
cortical disease.
Cogan's sign is a tonic deviation of the eye occurring on forced lid closure and associated with
lesions in the cerebral hemispheres.
Bilateral smooth pursuit deficit
Bilateral disorders are produced by diffuse posterior hemispheric, cerebellar or brainstem disease.
True smooth pursuit palsy with an absolute inability to track a moving target, in a patient with normal
fixation saccades, is extremely rare (Rowe, 2003).
Vestibulo-ocular Reflex
The purpose of the vestibulo-ocular reflex (VOR) is to keep the visual scene stable on the retina
despite head perturbations. These may occur during head motion alone or as a result of body motion as in
locomotion. There are two types of receptors, the three semicircular canals (anterior, posterior, and
horizontal; each sensing acceleration in its own plane) and the two otoliths (saccule and utricle; sensing
linear motion and head tilt) (Acheson & Riordan-Eva, 1999).
The Pathway originates in the labyrinths and proprioceptors in the neck muscles which mediate
information concerning head and neck movements. Afferent fibers synapse in the vestibular nuclei and pass
to the horizontal gaze centre in the PPRF (Kanski, 2007).
7
Supranuclear, Nuclear & Infranuclear
Fig. 3
Disorders of vistibulo-ocular reflex
A lesion of the semicircular canals or vestibular nerve will give rise to peripheral vestibular
nystagmus which worsens with removal of fixation. This Nystagmus has slow phases directed towards the
side of the lesion and if the whole nerve is involved it will be a mixture of horizontal and torsional
movements. If one semicircular canal or its connections are damaged then the Nystagmus will have a plane
of motion which is parallel to that of the damaged canal. Central vestibular Nystagmus is usually either
vertical or torsional (or some combination of the two). It is due to lesions of the vestibular nuclei,
vestibula-cerebellum or their onward connections, and does not worsen with removal of fixation.
Downbeat nystagmus may be thought of as a disorder of posterior canal connections and upbeat
nystagmus as a disorder of anterior canal projections. In both central and peripheral vestibular lesions
VOR gain will be disturbed, with a low gain toward the side of the lesion in peripheral disease and a
variable effect on gain with central lesions.
A unilateral lesion in the otolith pathway will give rise to an imbalance of graviception with a
consequent head tilt, tilt in the subjective visual vertical and combined torsion and skew deviation of the
eyes, the ocular tilt reaction (Acheson & Riordan-Eva, 1999).
Vergence
Vergence movements are disjugate and smooth. There is continuous control over the movement
generated. Vergence movements occur as synkinesis with accommodation and miosis. The medial and
lateral recti motoneurons are reciprocally innervated during vergence movements.
8
Supranuclear, Nuclear & Infranuclear
Higher control areas for the generation of vergence movements are poorly understood. Vergence
movements may occur as saccadic or smooth pursuit movements and therefore cortical areas relating to the
generation of these eye movement systems will be involved in the cortical processing of visual information
necessitating a vergence eye movement response.
Neurons for control of vergence have been found in mesencsphalic reticular formation (Judge &
Cumming 1986) which is dorsolateral to the III nerve nuclei and contains different types of neurons:
vergence tonic cells discharge in relation to vergence angle, vergence burst cells discharge in relation to
vergence velocity, vergence burst tonic cells discharge in relation to both vergence angle and velocity.
These cells may serve as a vergence integrator also. Lesions near the midbrain-diencephalic junction have
been documented in pseudo abducens palsy which has been proposed as a manifestation of abnormal
vergence activity.
Medial recti nuclei and VI nuclei discharge for vergence eye movements (Mays & Porter.1984).
Medial rectus motoneurons are organized into different groups: A, B & C. subgroup C may be specifically
involved in vergence commands. There is also some cerabellar input to vergence control. The nucleus
reticularis tegmenti pons (NRTP) houses neurons important for generating vergence position signal which
may therefore serve as a vergence neural integrator (Rowe, 2003).
Fig. 4
9
Supranuclear, Nuclear & Infranuclear
Disorders of vergence movement
Disorders of the vergence system are usually manifest as diplopia or a squint. If the defect is
acquired the patients usually complain of diplopia or aesthenopic symptoms due to the extra effort to
maintain single vision. If the defect is congenital or acquired prior to visual maturation, the diplopic image
may well be suppressed and the defect will be manifest as a squint at a particular viewing distance. Minor
head injury and febrile illnesses have been reported to result in symptomatically poor fusional vergence
with patients complaining of aesthenopic symptoms or frank diplopia. Thalamic lesions may on occasion
cause late-onset concomitant esotropia in childhood (Acheson & Riordan-Eva, 1999).
Convergence paralysis, divergence paralysis and spasm of the near reflex may result from disorders
of the vergence eye movement system. In certain brainstem conditions, such as INO, convergence may be
absent due to involvement of the convergence fibres in the pathological lesion.
Convergence paralysis
Convergence paralysis may be secondary to various organic processes such as encephalitis,
diphtheria, multiple sclerosis and occlusive vascular disease involving the rostral mid brain (Guiloff et al.
1980; Ohtsuka ct al. 2002). It may also occur in isolation as a sequela of a flu syndrome. Patients usually
present with exotropia and diplopia for near. They will have normal adduction of either eye. The deviation
can be said to be concomitant across the field of gaze.
Divergence paralysis
This may be associated with encephalitis, demyelinating disease, neurosyphilis, trauma and space
occupying lesions in and around the cerebellum (Chamlin & Davidoff 1951; Krohel et al. 1982; Roper-Hall
& Burde 1987). The patients appreciate diplopia on distance fixation and there is an esotropia demonstrable
on cover test for distance. There is normal abduction of either eye which differentiates the condition from
lateral rectus paresis (Cunningham 1972). If there are no other associated neurological factors, it is
considered benign and self-limiting (Rowe, 2003).
Divergence insufficiency
There is intermittent or constant esotropia at distance fixation with diplopia. A reduced fusional
divergence is noted (Rutkowsky & Burian 1972; Jacobsohn 2000). Prisms are usually beneficial and may
be reduced with time. Bilateral lateral rectus resection may be considered in cases where surgery is
required (Lyle,1954).
10
Supranuclear, Nuclear & Infranuclear
Spasm of near reflex
This involves convergence, accommodation and miosis and may be psychogenic. It is rarely due to
organic disease such as trauma, dorsal midbrain syndrome, intoxication and Wernicke's encephalopathy
(Dagi et al, 1987).
Horizontal gaze palsy
Horizontal eye movements are generated from the horizontal gaze centre in the PPRF (Fig.5). From
here motor neurons connect to the ipsilateral sixth nerve nucleus which innervates the lateral rectus.
From the sixth nerve nucleus internuclear neurons cross the midline at the level of the pons and
pass up the contralateral medial longitudinal fasciculus (MLF) to synapse with motor neurons in the medial
rectus sub nucleus in the third nerve complex which innervates the medial rectus.
Stimulation of the PPRF on one side therefore causes a conjugate movement of the eyes to the
same side. Loss of normal horizontal eye movements occurs when these pathways are disrupted.
Fig. 5
PPRF lesion gives rise to ipsilateral horizontal gaze palsy with inability to look in the direction of
the lesion. MLF lesion is responsible for the clinical syndrome of internuclear ophthalmoplegia (INO). A
left internuclear ophthalmoplegia is characterized by:
 Straight eyes in the primary position.
 Defective left adduction and ataxic nystagmus of the right eye on right gaze
 Left gaze is normal.
 Convergence is intact if the lesion is discrete; this may help to differentiate INO from
myasthenia.
 Vertical nystagmus on attempted up gaze.
11
Supranuclear, Nuclear & Infranuclear
Bilateral INO is characterized by:
 Limitation of right adduction and ataxic nystagmus of the left eye on left gaze.
 Limitation of left adduction and ataxic nystagmus of the right eye on right gaze.
 Convergence is usually intact if the lesion is discrete but may he absent if the lesion is
extensive.
PPRF and MLF combined lesions on the same side give rise to the 'one-and-a-half syndrome'
which is characterized by a combination of ipsilateral gaze palsy and INO so that the only residual
movement is abduction of the contra lateral eye which also exhibits ataxic nystagmus (Kanski, 2007).
Vertical gaze palsy
Vertical eye movements are generated from the vertical gaze centre (rostral interstitial nucleus of
the MLF) which lies in the midbrain just dorsal to the red nucleus. From the vertical gaze centre, impulses
pass to the sub-nuclei of the eye muscles controlling vertical gaze in both eyes. Cells mediating upward and
downward eye movements are intermingled in the vertical gaze centre, although selective paralysis of upgaze and down-gaze may occur in spite of this (Kanski, 2007).
12
Supranuclear, Nuclear & Infranuclear
Nuclear & Infranuclear Control and Disorders
Third Nerve
Nuclear complex and disorder
The nuclear complex of the third (oculomotor) nerve is situated in the midbrain at the level of the
superior colliculus, ventral to the sylvian aqueduct (Fig.6). It is composed of the following paired and
unpaired subnuclei:
1. Levator subnucleus is an unpaired caudal midline structure which innervates both levator
muscles. Lesions confined in this area will therefore give rise to bilateral ptosis.
2. Superior rectus subnuclei are paired: each innervates the respective contralateral superior
rectus. Nuclear third nerve palsy will spare the ipsilateral and affect the contralateral
superior rectus.
3. Medial rectus, inferior rectus and inferior oblique sub-nuclei are paired and innervate
their corresponding ipsilateral muscles. Lesions confined to the nuclear complex are
relatively uncommon. The most frequent causes are vascular disease, primary tumours and
metastases. Involvement of the paired medial rectus sub-nuclei cause a wall-eyed bilateral
Inter-nuclear ophthalmoplegia (WEBINO), characterized by exotropia, and defective
convergence and adduction. Lesions involving the entire nucleus are often associated with
involvement of the adjacent and caudal fourth nerve nucleus (Kanski, 2007).
Fig. 6
13
Supranuclear, Nuclear & Infranuclear
Fasciculus
The fusclculus consists of efferent fibres which pass from the third nerve nucleus through the red
nucleus and the medial aspect of the cerebral peduncle. They then emerge from the midbrain and pass into
the interpeduncular space.
The causes of nuclear and fascicular lesions are similar, except that demyelination may affect the
fasciculus.
1. Benedikt syndrome Involves the fasciculus as it passes through the red nucleus and is
characterized by ipsilateral third nerve palsy and contralateral extrapyramidal signs such as
hemitremor.
2. Weber syndrome involves the fasciculus as it passes through the cerebral peduncle and is
characterized by ipsilateral third nerve palsy and a contralateral hemiparesis.
3. Nothnagel syndrome involves the fasciculus and the superior cerebellar peduncle and is
characterized by ipsilateral third nerve palsy and cerebellar ataxia. Important causes include
vascular disease and tumours.
4. Claude syndrome is a combination of Benedikt and Nothnagel syndromes.
Basilar
The basilar part starts as a series of 'rootlets' which leave the midbrain on the medial aspect of the
cerebral peduncle, before coalescing to form the main trunk. The nerve then passes between the posterior
cerebral and superior cerebellar arteries, running lateral to and parallel with the posterior communicating
artery (Fig.7). As the nerve traverses the base of the skull a long its subarachnoid course unaccompanied by
any other cranial nerve, isolated third nerve palsies are commonly basilar. The following two are
Important causes:
1. Aneurysm of the posterior communicating artery at its junction with the internal carotid artery.
Typically presents as acute, painful third nerve palsy with involvement of the pupil.
2. Head trauma, resulting in extradural or subdural haematoma, may cause a tentorial pressure cone
with downward herniation of the temporal lobe. This compresses the third nerve as it passes over
the tentorial edge, initially causing irritative miosis followed by mydriasis and total third nerve
palsy.
Fig. 7
14
Supranuclear, Nuclear & Infranuclear
Intracavernous
The third nerve then enters the cavernous sinus by piercing the dura just lateral to the posterior
clinoid process. Within the cavernous sinus, the third nerve runs in the lateral wall above the fourth nerve
(Fig.8). In the anterior part of the cavernous sinus, the nerve divides into superior and inferior branches
which enter the orbit through the superior orbital fissure within the annulus of Zinn. The following are
important causes of intracavernous third nerve palsies:
1. Diabetes, which may cause a vascular palsy, which usually spares the pupil.
2. Pituitary apoplexy (haemorrhagic Infarction) may cause a third nerve palsy (e.g. after
childbirth) if the gland swells laterally and impinges on the cavernous sinus.
3. Intracavernous pathology such as aneurysm, meningioma, carotid-cavernous fistula and
granulomatous inflammation (Tolosa- flunt syndrome ) may all cause third nerve palsy
Because of its close proximity to other cranial nerves. intracavernous third nerve palsies are
usually associated with involvement of the fourth and sixth nerves, and the first division of
the trigeminal nerve. (Kanski, 2007).
Fig. 8
Intraorbital
1. Superior division innervates the levator and superior rectus muscles.
2. Inferior division Innervates the medial rectus, the inferior rectus and the inferior oblique muscles.
The branch to the inferior oblique also contains preganglionic parasympathetic fibres from the
Edinger-Westphal subnucleus, which innervate the sphincter pupillae and the ciliary muscle.
Lesions of the inferior division are characterized by limited adduction and depression, and a dilated pupil.
Both superior and inferior division palsies are commonly traumatic or vascular.
15
Supranuclear, Nuclear & Infranuclear
Pupillomotor ftbres
Between the brainstem and the cavernous sinus, the pupillomotor parasympathetic fibres are located
superficially in the superomedial part of the third nerve (Fig.9).They derive their blood supply from the pial
blood vessels, whereas the main trunk of the third nerve is supplied by the vasa nervorum. Involvement or
otherwise of the pupil is of great importance because it frequently differentiates a 'surgical' from a 'medical'
lesion. Pupillary involvement, like other features of third nerve palsy, may be complete or partial, and
may demonstrate features of recovery. Mild mydriasis and non-reactivity may therefore be clinically
significant (Kanski, 2007).
Sometimes pupillary involvement may be the only sign of third nerve palsy (basal meningitis,
uncal herniation).
Fig. 9
Signs of a right third nerve palsy:
 Weakness of the levator causing profound ptosis, due to which there is often no diplopia.
 Unopposed action of lateral rectus causing the eye to be abducted in the primary position.
 The intact superior oblique muscle causes intorsion of the eye at rest, which increases on






attempted downgaze.
Normal abduction because the latera l rectus is intact.
Weakness of the medial rectus limiting adduction.
Weakness of superior rectus and inferior oblique, limiting elevation.
Weakness of inferior rectus limiting depression.
Parasympathetic palsy causing a dilated pupil associated wit h defective accommodation.
Partial involvement will produce milder degrees of ophthalmoplegia.
16
Supranuclear, Nuclear & Infranuclear
Fourth Nerve
Anatomy
Important features of the fourth (trochlear) nerve are the following:
 It is the only cranial nerve to emerge from the dorsal aspect of the brain.
 It is a crossed cranial nerve; this means that the fourth nerve nucleus innervates the
contralateral superior oblique muscle.
 It is a very long and slender nerve.
The nucleus of the fourth nerve is located at the level of the inferior colliculi ventral to the sylvian
aqueduct (Fig.10). It is caudal to, and continuous with the third nerve nuclear complex.
The fasciculus consists of axons which curve posteriorly around the aqueduct and decussate completely
in the anterior medullary velum.
The trunk leaves the brainstem on the dorsa l surface, just caudal to the inferior colliculus. It then curves
laterally around the brainstem, runs forwards beneath the free edge of the tentorium, and (like the third
nerve) passes between the posterior cerebral artery and the superior cerebellar artery. It then pierces the
dura and enters the cavernous sinus.
The intracavernous part runs in the lateral wall of the sinus, inferiorly to the third nerve and above the
first division or the fifth. In the anterior part of the cavernous sinus it rises and passes through the superior
orbital fissure above and lateral to the annulus of Zinn
Fig. 10:
17
Supranuclear, Nuclear & Infranuclear
The intraorbital part innervates the superior oblique muscle.
Fourth nerve palsy:
Acute onset of vertical diplopia in the absence of ptosis, combined with a characteristic head
posture, strongly suggests fourth nerve disease. The features of nuclear, fascicular and
peripheral fourth nerve palsies are clinically identical, except that nuclear palsies produce contralateral
superior oblique weakness. (Kanski, 2007).
Signs of a left fourth nerve palsy:
 Left hypertropia ('left over right') in the primary position when the uninvolved right eye is fixating




due to weakness of the left superior oblique.
Left limitation in depression in adduction due to superior oblique weakness.
Excyclotorsion.
Diplopia which is vertical, torsional and worse on looking down .
The left hypertropia increases on right gaze due to left inferior oblique overaction.
Sixth Nerve
Nucleus
The nucleus of the sixth (abducens) nerve lies at the mid level of the pons, ventral to the floor of the
fourth ventricle, where it is closely related to the horizontal gaze centre. The fasciculus of the seventh nerve
curves around the abducent nucleus and produces an elevation in the floor of the fourth ventricle (facial
colliculus) (Fig. 11). Isolated sixth nerve palsy is therefore never nuclear in origin. A lesion in and around
the sixth nerve nucleus causes the following signs:
• Ipsilateral weakness of abduction as a result of involvement of the sixth nerve.
• Failure of horizontal gaze towards the side of the lesion resulting from involvement of the
horizontal gaze centre in the pontine paramedian reticular formation (PPRF).
• Ipsilateral lower motor neuron facial nerve palsy caused by concomitant involvement of the facial
fasciculus is common.
Fig. 11
18
Supranuclear, Nuclear & Infranuclear
Fasciculus
The fasciculus passes ventrally to leave the brainstem at the pontomedullary junction, jusl lateral to
the pyramidal prominence.
Foville syndrome involves the fasciculus as it passes through the PPRF and is most
frequently caused by vascular disease or tumours involving the dorsal pons. It is characterized by ipsilateral
involvement of the fifth to eighth cranial nerves and central sympathetic fibres.
• Fifth nerve - facial analgesia.
• Sixth nerve palsy combined with gaze palsy (PPRF).
• Seventh nerve (nuclear or fascicular damage) – facial weakness.
• Eighth nerve - deafness.
• Central Horner syndrome.
Millard- Gubler syndrome involves the fasciculus as it passes through the pyramidal tract and is
most frequently caused by vascular disease, tumours or demyelination. It is characterized by the following:
• Ipsilateral sixth nerve palsy.
• Contralateral hemiplegia (since the pyramidal tracts decussate further inferiorly, in the medulla, to
control contralateral voluntary movement).
• Variable number of signs of a dorsal pontine lesion (Kanski, 2007).
Basilar
The basilar part leaves the brainstem at the pontomedullary junction an d enters the prepontine
basilar cistern. It then passes upwards close to the base of the skull and is crossed by the anterior inferior
cerebellar artery (Fig.12). It pierces the dura below the posterior clinolds and angles forwards over the tip
of the petrous bone, passing through or around the inferior petrosal sinus, through Dorello canal (under the
pctrocIinoid ligament), to enter the caver nous sinus.
Fig. 12:
19
Supranuclear, Nuclear & Infranuclear
Intracavernous
The intracavernous part runs forwards below the third and fourth nerves, as well as the first division
of the fifth. Although the other nerves are protected within the wall of the sinus, the sixth is most medially
situated and runs through the middle of the sinus in close relation to the internal carotid artery. It is
therefore more prone to damage than the other nerves. Occasionally, an intracavernous sixth nerve palsy is
accompanied by a postganglionic Horner syndrome (Parkinson sign) because in its intracavernous course
the sixth nerve is joined by sympathetic branches from the para carotid plexus. The causes of
intracavernous sixth nerve and third nerve lesions are similar (Kanski, 2007).
Intraorbital
The intraorbital part enters the orbit through the superior orbital fissure within the annulus of Zinn
to innervate the lateral rectus muscle.
Signs of a left sixth nerve palsy:
 Left esotropia in the primary position due to unopposed action of the left medial
rectus.
 Esotropia is characteristically worse for a distant target and less or absent for near
fixation.
 Marked limitation of left abduction due to weakness of the left lateral rectus.
 Normal left adduction (Kanski, 2007).
Ophthalmoplegia
This is a group of conditions which have a variety of causative factors, where there is a paresis of
two or more extraocular muscles.
Cavernous sinus syndrome
There is a lesion in the cavernous sinus causing paresis of the ocular motor nerves and the first two
divisions of the V nerve (Hunt et al, 1961).
Papillary reaction is often spared. Ophthalmoplegia is due to involvement of the III, IV and VI
nerves. Ptosis may be evident.
Sphenoidal fissure syndrome
A lesion in the region of the superior orbital fissure may affect any structure passing through.
Diplopia is due to III, IV and VI nerves involvement. Pain and anaesthesia is due to involvement of V
nerve.
20
Supranuclear, Nuclear & Infranuclear
Orbital apex syndrome
A lesion in the posterior part of the orbit near its apex is responsible for this condition. V nerve
involvement causes sever pain. Reduced visual acuity is due to compression of the optic nerve. Limited
ocular motility is seen with III, IV and VI nerves involvement.
Guillain-Barre syndrome (Fisher’s syndrome)
Fisher’s syndrome is characterized by total external ophthalmoplegia, ataxia and hyporeflexia.
Ophthalmoplegia involves symmetrical impairment of conjugate upward and lateral gaze progressing
frequently to complete ophthalmoplegia (Rowe, 2003).
Tolosa-Hunt syndrome
This is an inflammatory condition that involves the superior orbital fissure or the anterior cavernous
sinuses resulting in a painful ophthalmoplegia. Ophthalmoplegia is with complete or partial palsy of EOM
and the pupil may or may not be affected.
Ocular neuromyotonia
This is a rare condition resulting in a transient, aperiodic ocular misalignment. It is due to
spontaneous firing of ocular motor nerves resulting in impairment of muscle relaxation.
Moebius’ syndrome
This congenital condition may be due to a primary developmental defect of the central nervous
system with aphasia of motor nuclei of the VI and VII nerves and denervation atrophy of facial and EOM.
(Rowe, 2003).
21
Supranuclear, Nuclear & Infranuclear
References
Acheson, J. & Riordan-Eva, P. (1999): Fundamental of clinical ophthalmology: neuroophthalmology. London: BMJ Books.
Bartley, G.B. & Liesegang, T.J.(1992): Essential of ophthalmology. Philadelphia:
Lippincott company.
Kanski, J.J.(2007): Clinical ophthalmology: a systimatic approach. Philadelphia: Elsevier
limited.
Rowe, F. (2004). Clinical orthoptics (2nd ed.). Oxford: Blackwell Publishing.
22