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Chapter 198 – Nuclear and Fascicular Disorders of Eye Movement

Chapter 198 – Nuclear and Fascicular Disorders of Eye Movement

 

SEAN P. DONAHUE

 

 

 

 

 

DEFINITION

• Eye movement disorders caused by damage to the ocular motor nerve nuclei (cranial nerve III, IV, or VI) or to the ocular motor nerve fascicles within the brainstem as they travel from the nerve nucleus to the subarachnoid space.

 

KEY FEATURES

• Diplopia.

• Incomitant ocular deviation.

• Other localizing neurological signs.

 

ASSOCIATED FEATURES

• Other cranial nerve palsies.

• Supranuclear disorders of motility.

• Long tract signs.

 

 

 

INTRODUCTION

Eye movement commands are carried from the cerebral cortex and higher brainstem structures to the ocular motor nerve nuclei. These commands are then sent to the individual extraocular muscles by cranial nerves III, IV, and VI. Eye movement abnormalities resulting from damage to the structures that carry commands to the ocular motor nerve nuclei are considered supranuclear or prenuclear in origin (see Chapter 197 ). Abnormalities resulting from damage to the ocular motor nuclei and their respective cranial nerves are considered infranuclear.

An infranuclear ocular motor nerve palsy can be caused by damage to the nerve anywhere from the nucleus to the extraocular muscle it innervates. Nuclear ocular motor palsies occur at the level of the ocular motor nucleus, whereas fascicular nerve palsies are caused by lesions of the fascicle of nerve that travels through the brainstem from the nerve nucleus to its exit into the subarachnoid space.

Nuclear and fascicular ocular motor nerve palsies produce characteristic ocular abnormalities according to the function of the innervated structure. All acute palsies produce an incomitant strabismus that is greatest in the field of action of the paretic muscle. Palsies of the third nerve are typically associated with abnormal pupillary and lid function, in addition to ocular motility abnormalities. Fourth nerve palsies are associated almost always with additional complaints of torsion or a head tilt.

Nuclear and fascicular nerve palsies often are associated with other neurological signs because of the large number of structures located nearby ( Fig. 198-1 ). A detailed knowledge of the neuroanatomy of the midbrain and pons enables the clinician to localize these lesions with great accuracy.

 

 

Figure 198-1 Location of ocular motor nerve nuclei and fascicles in the brainstem. Note the relationship of the cranial nerve nuclei and fascicles to the medial longitudinal fasciculus, red nucleus, paramedian pontine reticular formation, and facial nerve nucleus and fascicle. The fourth nerve exits dorsally, while the third and sixth nerves exit ventrally.

EPIDEMIOLOGY AND PATHOGENESIS

Multiple reports in the literature document the causes of palsies of the three cranial nerves that subserve eye movements.[1] [2] [3] [4] However, ocular motor nerve palsies typically become apparent in one of the following four ways[5] :

• Truly isolated nerve palsies that have no other signs or symptoms

• Isolated nerve palsies that have associated symptoms

• Nerve palsies associated with palsies of other cranial nerves

• Nerve palsies with neurological signs other than cranioneuropathies

Each of these four groups has a different corresponding differential diagnosis. Reports in the literature that consider the causes of ocular motor nerve palsies generally do not classify the palsies in this manner. Thus, most of these reports are of limited value to the clinician, who may have either localized the lesion already or formulated a differential diagnosis based on the manner of appearance.

 

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Causes of Nucleur and Fascicular Third Cranial Nerve Palsies

 

CHILDREN

Congenital

 

• with neurological abnormalities

• with aberrant reinnervation

• with cyclic oculomotor spasm

Vascular (arteriovenous malformation)

 

Primary tumor

 

Metastatic tumor

 

 

YOUNG ADULTS

Demyelinating

 

Vascular (hemorrhage or infarction)

 

Tumor

 

 

OLDER ADULTS

Vascular (infarction)

 

Tumor

 

 

 

 

 

 

 

Causes of Nucleur and Fascicular Fourth Cranial Nerve Palsies

 

INTRINSIC MIDBRAIN LESIONS

Trauma (anterior medullary velum)

 

Tumor

 

• Medulloblastoma

• Ependymoma

• Metastatic

Demyelination

 

Stroke

 

• Ischemic

• Hemorrhagic

Arteriovenous malformation

 

 

EXTRINSIC MIDBRAIN LESIONS

Tumor

 

• Pinealoma

• Metastatic

Hydrocephalus

 

Aqueductal stenosis

 

 

 

 

 

 

 

Causes of Nucleur and Fascicular Sixth Cranial Nerve Palsies

Vascular disease

 

• Hemorrhage

• Infarction (anterior inferior cerebellar artery paramedian perforating arteries)

Demyelinating disease

 

Trauma

 

Tumor

 

• Glioma

• Astrocytoma

• Ependymoma

• Medulloblastoma

• Metastatic

• Infiltrative

Other

 

 

 

 

Because nuclear and fascicular disorders have associated findings that make them highly localizable, it is better to localize the lesion and then consider the causes based on the patient’s age and the history ( Boxes 198-1 to 198-3 ). Most nuclear and fascicular disorders of eye movement are caused by vascular disease (infarction, hemorrhage from arteriovenous malformation), demyelination, and tumor (metastatic or primary). Infectious, inflammatory, and traumatic causes are much less likely. Congenital oculomotor nerve palsy can arise from brainstem disorders in some patients,[6] [7] [8] who often have other brain anomalies and brainstem syndromes. Although thyroid disease and myasthenia can mimic isolated cranial nerve palsies, neither is associated with neurological deficits of brainstem function.

OCULAR MANIFESTATIONS

Palsies of the Third Cranial Nerve

The oculomotor nerve innervates the levator palpebrae, the pupillary sphincter, and the following four extraocular muscles:

• Medial rectus

• Inferior rectus

• Superior rectus

• Inferior oblique

The degree of involvement of these six structures varies in patients who have third nerve palsies. When the palsy is complete, there is complete ptosis with a dilated pupil that responds neither to light nor near. The eye is deviated out and usually, but by no means always, down. Function of the other ocular motor nerves can be assessed in this situation by evaluation of abduction (sixth cranial nerve) and by observing incyclotorsion on attempted depression (fourth cranial nerve).

Nuclear Third Cranial Nerve Lesions

The third nerve nucleus is located in the midbrain near the cerebral aqueduct at the level of the superior colliculus ( Fig. 198-2 ). The anatomy of the third nerve nucleus was described by Warwick [9] in a classic paper in 1953. Each extraocular muscle that receives innervation from the third nerve has a corresponding group of cells, called a subnucleus, in the third nerve nucleus ( Fig. 198-3 ). A single central nucleus (central caudal nucleus) innervates both levator palpebrae muscles. Distinct, bilateral subnuclei exist for the left and right medial recti, inferior recti, superior recti, and inferior oblique muscles. An additional bilateral subnucleus, the Edinger–Westphal nucleus, provides parasympathetic input to the pupillary sphincter.

Projections from the subnuclei to their targets all are uncrossed (each subnucleus innervates the ipsilateral corresponding extraocular muscle), with two exceptions—the single central caudal nucleus sends projections to both levator muscles, and the superior rectus subnucleus projection is crossed. Thus, the right superior rectus subnucleus innervates the left superior rectus muscle, and vice versa.

The rationale for the crossing of the fibers of the superior rectus subnucleus to the contralateral superior rectus is not understood fully but may be to facilitate vestibular innervation. The trochlear nerve also undergoes a decussation. As a result, each cyclovertical muscle and its corresponding yoked muscle pair have nuclei on the same side of the brain. The right inferior oblique subnucleus and left superior rectus subnucleus are both located on the right; the left inferior rectus subnucleus and right superior oblique subnucleus are both located on the left. This allows the direct innervation of a yoked muscle pair from the corresponding semicircular canal without a decussation; it may have been important in the development of the vestibular–ocular counter-rolling reflex (see Chapter 197 ).

Although the anatomy of the third nerve nucleus is quite complex, it does allow precise localization when certain abnormalities are present. Daroff [10] has proposed clinical rules that obligate or exclude nuclear involvement ( Box 198-4 ). Because the central caudal subnucleus sends projections to both levator muscles, a bilateral third nerve palsy that spares the lid on both sides obligates a (rostral) nuclear lesion. The crossed projection of the superior rectus subnucleus also is important in the localization of these lesions—unilateral third nerve lesions that have

 

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Figure 198-2 Anatomy of midbrain at the level of the third cranial nerve nucleus. The fascicles of the third nerve pass through the red nucleus, substantia nigra, and crus cerebri before they exit into the interpeduncular fossa. The medial lemniscus is nearby. Note the intimate relationship of the oculomotor nerve nuclei to the medial longitudinal fasciculus, periaqueductal gray, and the cerebral aqueduct.

involvement of the contralateral superior rectus obligate a nuclear lesion, whereas a third nerve palsy with no contralateral superior rectus abnormality cannot be caused by a nuclear lesion. The reader should review Daroff’s rules (see Box 198-4 ) and determine how the neuroanatomy is responsible for each rule.

Isolated nuclear third nerve lesions are quite rare. Usually the lesion extends to cause supranuclear disorders of vertical gaze and other neurological signs. However, Warwick’s scheme of nuclear anatomy has received confirmation by magnetic resonance imaging documentation in patients who have obligatory nuclear third nerve palsies[11] [12] [13] ; histopathological confirmation also has been reported.[14] [15]

Infarction, usually of small branches of the basilar artery, is the cause of most nuclear third nerve palsies. Metastatic, lymphoproliferative, and primary neoplastic disease also can occur.

Fascicular Third Cranial Nerve Palsies

After leaving the nucleus, the axons of the oculomotor neurons travel through the midbrain and exit ventrally. They pass near or through two important structures before exiting into the subarachnoid space of the interpeduncular fossa—the red nucleus and the crus cerebri. Lesions that damage the third nerve fascicle within the red nucleus cause a contralateral intention tremor and ataxia. Because the nearby medial lemniscus carries sensory fibers for light touch and proprioception on the contralateral side, these modalities also may be impaired or absent. Lesions of the cerebral peduncle damage corticospinal tract fibers that descend to innervate the musculature of the contralateral extremities; damage in this area is associated with a contralateral hemiparesis. Each of these syndromes has a specific eponym ( Table 198-1 ).

 

 

Figure 198-3 Anatomy of the third cranial nerve nucleus. The third nerve nucleus consists of a single, central, caudally located nucleus for the levator palpebrae, paired bilateral subnuclei with crossed projections that innervate the superior recti, and paired bilateral subnuclei with uncrossed projections that innervate the medial recti, inferior recti, and inferior oblique muscles. Parasympathetic input to the ciliary body and iris sphincter arises from the Edinger–Westphal nucleus. (Redrawn from Warwick R. Representation of the extraocular muscles in the oculomotor nuclei of the monkey. J Comp Neurol. 1953;98:449–503.)

 

 

 

Daroff’s Rules for Nucleur Third Cranial Nerve Palsies*

 

CONDITIONS THAT OBLIGATE NUCLEAR INVOLVEMENT

Bilateral third nerve palsy without ptosis (bilaterally spared levator function)

 

Unilateral third nerve palsy with contralateral superior rectus abnormality and bilateral partial ptosis

 

 

CONDITIONS THAT EXCLUDE A NUCLEAR LESION

Unilateral ptosis

 

Unilateral internal ophthalmoplegia

 

Unilateral external ophthalmoplegia associated with normal contralateral superior rectus function

 

 

CONDITIONS THAT NEITHER EXCLUDE NOR OBLIGATE A NUCLEAR LESION

Bilateral total third nerve palsy

 

Bilateral ptosis

 

Bilateral internal ophthalmoplegia

 

Bilateral medial rectus palsy

 

 

From Daroff RB. Oculomotor manifestation of brainstem and cerebellar dysfunction. In: Smith JL, ed. Neuro-ophthalmology: symposium of the University of Miami and Bascom-Palmer Eye Institute, vol 5. Hallandale: Huffman; 1971:104–21.

 

* Isolated unilateral single muscle involvement (except levator and superior rectus).

 

 

 

Classically, fascicular third nerve palsies were thought to affect all functions of the third nerve equally, with the degree of pupil involvement (anisocoria increasing in bright light) being proportional to the lid and motility defects. Recently, however, it has been recognized that isolated extraocular muscle pareses, especially inferior rectus paresis, can result from fascicular third nerve lesions.[16] [17] Divisional oculomotor paresis also can be

 

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TABLE 198-1 — SYNDROMES OF THE FASCICULAR THIRD CRANIAL NERVE

Location

Eponym

Findings

Red nucleus

Benedikt’s

Intention tremor, ataxia, contralateral sensation loss (if medial lemniscus Involved)

Crus cerebri

Weber’s

Contralateral hemiparesis

 

 

caused by brainstem disease.[18] Three cases of pupil-sparing third nerve palsy associated with midbrain vascular disease also have been reported,[19] [20] and it is possible that the “isolated,” pupil-sparing third nerve palsy seen in adults who have diabetes mellitus results from fascicular damage.[21]

Most fascicular third nerve lesions have vascular causes (hemorrhage, infarction). Metastatic or infiltrative disease is less common; demyelinating disease is rare, even in patients who have known multiple sclerosis. Because fascicular third nerve palsies are typically ischemic in nature, they may have varying degrees of recovery. Aberrant regeneration, however, does not occur. Patients who have aberrant regeneration after an acquired third nerve palsy must be considered to have a compressive lesion of the third nerve.

Congenital Third Cranial Nerve Palsies

Congenital oculomotor nerve palsies are rare and are associated with neurological abnormalities in a significant percentage of patients. [6] [7] [8] These palsies can result from aplasia or hypoplasia of the oculomotor nucleus,[22] but more often they occur because of lesions of the nerve itself. Aberrant regeneration following congenital third nerve palsies is rather common,[23] which argues against a nuclear lesion. Loewenfeld and Thompson[24] have speculated that perinatal damage to the third nerve causes retrograde degeneration of the oculomotor nucleus, which then is reinnervated haphazardly. Patients who have congenital third nerve palsies and associated neurological abnormalities without aberrant regeneration likely have brainstem pathology.

Some patients who have congenital oculomotor nerve palsies develop cyclic oculomotor spasm.[24] Typical cases have a slow alternation between a paretic phase, in which the lid droops, the pupil dilates, and the eye turns out, and a spastic phase, in which the lid elevates, the pupil constricts, accommodation occurs, and the eye adducts. These cycles usually persist throughout life. Cyclic oculomotor spasm usually is not associated with acquired lesions of the third nerve.

Palsies of the Fourth Cranial Nerve

Superior oblique palsy is the most common cause of acquired vertical diplopia and can be either congenital or acquired. Patients who have acquired superior oblique palsies have diplopia that is often worse in downgaze, and they usually complain of torsion. Subjective image separation increases with gaze in the direction opposite the side of the palsy and with head tilt toward the side of the palsy. For example, a right superior oblique palsy has diplopia worse on left gaze and right head tilt. Motility testing in the acute phase usually demonstrates poor depression in adduction. Orthoptic measurements show a hypertropia of the affected eye that increases with gaze to the side opposite the palsy and with head tilt toward the side of the palsy. The most common cause of an isolated, acquired fourth nerve palsy is trauma (see Box 198-2 ).[25] [26] [27]

Congenital fourth nerve palsies can become apparent at any age. Young children often exhibit abnormal head postures, while older individuals typically experience intermittent vertical diplopia. Patients who have congenital fourth nerve palsies have large vertical fusional amplitudes, usually greater than 10 prism diopters, and old photographs demonstrate a consistent head tilt, usually away from the side of the palsy. Motility often is full in these patients; overelevation in adduction with a corresponding hypotropia of the abducting eye on alternate cover test (inferior oblique overaction) also is relatively common. Orthoptic testing yields results similar to those for acquired fourth nerve palsies.

Three unique clinical points exist that need to be remembered about the trochlear nerve. It is the only cranial nerve to exit dorsally; all others exit ventrally. It undergoes an immediate decussation in the anterior medullary velum and thus innervates the contralateral superior oblique muscle. Finally, the fourth nerve has the longest intracranial course of any cranial nerve.

Although both congenital and acquired fourth nerve palsies usually are isolated, additional neuro-ophthalmologic findings occasionally are present that help to localize the lesion and determine whether imaging studies are warranted. The fourth nerve fasciculus is quite short, because the nerve exits the brainstem dorsally, and most brainstem fourth nerve palsies usually involve both the nucleus and fasciculus. Thus, the nuclear and fascicular lesions have been combined in the following discussion.

Nuclear and Fascicular Fourth Cranial Nerve Lesions

The fourth nerve nucleus is in the midbrain at the level of the inferior colliculus (see Fig. 198-1 ). It lies just caudal to the third nerve nucleus and receives prenuclear input from the vestibular system, the medial longitudinal fasciculus, and the rostral interstitial medial longitudinal fasciculus (riMLF). The fasciculus of the trochlear nerve travels dorsally to exit the lower midbrain just caudal to the inferior colliculus, near the tentorium. Because the nerve decussates in the anterior medullary velum, nuclear and fascicular fourth nerve palsies are associated with superior oblique dysfunction on the contralateral side.

Isolated lesions that affect only the nuclear or fascicular trochlear nerve are very rare. Most lesions of the area that surrounds the fourth nerve nucleus and fasciculus also affect neighboring structures. Both extrinsic (tumor, hydrocephalus) and intrinsic (tumor, stroke, demyelination, arteriovenous malformation) lesions of the brainstem may damage the trochlear nerves or nucleus and often produce an associated upgaze palsy or features of the dorsal midbrain syndrome (see Box 198-2 ). Lesions that damage the fourth nerve within the dorsolateral midbrain also can damage the first-order (descending) sympathetic fibers ( Table 198-2 ). Affected patients have an ipsilateral preganglionic Horner’s syndrome and a contralateral superior oblique palsy.[28] Lesions that extend into the superior cerebellar peduncle have an associated ipsilateral dysmetria. Damage that extends into the medial longitudinal fasciculus can produce an ipsilateral internuclear ophthalmoplegia in association with a superior oblique palsy. The hypertropia can be misdiagnosed as a skew deviation unless careful attention is paid to measurements of head tilt and to objective and subjective torsion. Damage to both trochlear nerve fascicles at their decussation within the anterior medullary velum usually results from trauma and produces a bilateral superior oblique palsy, which is often asymmetrical. These patients typically have a V-pattern esotropia, a right hypertropia on left gaze, a left hypertropia on right gaze, and greater than 10 degrees of subjective excyclotorsion when measured with the double Maddox rod. Bilateral fourth nerve palsy also can be produced by brainstem hematoma, but this is much rarer.[29]

Perhaps the most interesting fascicular syndrome of the fourth nerve involves the brachium of the superior colliculus.[30] Through this structure pass pupillomotor fibers as they travel from the optic tract to the pretectum. These fibers subserve the pupillary light reflex from the contralateral visual field. Because the retinogeniculate pathway has already separated from the pupillary pathways, conscious light detection is not affected, but the pupillary light

 

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TABLE 198-2 — NUCLEAR AND FASCICULAR SYNDROMES OF THE FOURTH CRANIAL NERVE

Site of Damage

Laterality of Superior Oblique Palsy

Clinical Manifestations

Pretectal area

Contralateral

Vertical gaze palsy

Dorsal midbrain syndrome

Descending sympathetic pathways

Contralateral

Ipsilateral Horner’s syndrome

Superior cerebellar peduncle

Contralateral

Ipsilateral dysmetria

Medial longitudinal fasciculus

Contralateral

Ipsilateral internuclear ophthalmoplegia

Brachium of superior colliculus

Contralateral

Contralateral relative afferent pupillary defect

Contralateral pupil homonymous hemianopia

Normal visual fields

Anterior medullary velum

Bilateral

‘V’ pattern esotropia

Reversing hypertropias on side gaze

>10° excyclotorsion

 

 

reflex is. Patients who suffer lesions in this area have normal visual fields but a small (0.6–0.9 log unit) relative afferent pupillary defect in the eye contralateral to the lesion, consistent with an optic tract lesion. The fourth nerve palsy is also on the contralateral side (the fascicle is damaged before the decussation). For example, a patient who has a right-sided lesion will have a left hypertropia that maps to a left superior oblique palsy and a small relative afferent pupillary defect in the left eye. If performed, pupil fields would demonstrate a left homonymous hemianopia, while formal visual fields would be full.

Palsies of the Sixth Cranial Nerve

The sixth nerve innervates the ipsilateral lateral rectus muscle and produces abduction. Damage to the sixth nerve produces an esotropia that is worse in the field of action of the involved sixth nerve. The esotropia usually is greater at distance than at near. Most patients are able to fuse with a face turn toward the side of the palsy (gaze away from the palsy). The pupil is not affected. Patients who have long-standing sixth nerve palsies can develop tightening and contracture of the medial rectus, which causes a restrictive strabismus with positive forced ductions. Occasionally, patients who have long-standing sixth nerve palsies may have associated vertical diplopia and hypertropia.[31]

Although patients who suffer sixth nerve palsies have a characteristic abduction deficit, it must be recognized that all abduction deficits are not due to sixth nerve palsies. Orbital lesions, medial wall fractures, Duane’s syndrome, thyroid disease, and myasthenia all can mimic sixth nerve palsies.

The sixth nerve can be damaged at any location between its nucleus and the lateral rectus muscle. In a manner similar to the case with third nerve palsies, nuclear and fascicular lesions of the sixth nerve typically have characteristic findings that make them highly localizable.

Nuclear Sixth Cranial Nerve Palsies

The sixth nerve nucleus is in the pons, just ventral to the floor of the fourth ventricle. The fascicle of the facial nerve wraps around the sixth nerve nucleus ( Fig. 198-4 ). The sixth nerve nucleus contains cell bodies of two types of neurons—most cell bodies

 

 

Figure 198-4 Anatomy of sixth cranial nerve nucleus in the pons. The abducens nucleus is surrounded by the facial nerve fasciculus after it originates from its nucleus and is associated intimately with the medial longitudinal fasciculus. Abducens fascicles traverse the paramedian pontine reticular formation and the corticospinal tract before leaving the lower ventral pons. The vestibular nuclei and spinal nucleus and tract of the trigeminal nerve are nearby in the lateral pons.

 

 

 

Nuclear and Fascicular Syndromes of the Sixth Cranial Nerve

 

NUCLEAR SIXTH NERVE PALSIES

One-and-a-half syndrome (obligate)

 

Foville’s syndrome

 

Gaze palsy

 

Peripheral facial palsy (likely)

 

 

FASCICULAR SIXTH NERVE PALSIES

With contralateral hemiplegia (Raymond’s syndrome)

 

Facial weakness (Millard–Gubler syndrome)

 

 

 

 

project directly to the lateral rectus muscle, via the abducens nerve. However, about 40% of the cells in the abducens nucleus are interneurons which project, via the medial longitudinal fasciculus, to the contralateral medial rectus subnucleus, and cause adduction of the contralateral eye. Thus, the sixth nerve nucleus, like the paramedian pontine reticular formation, is a gaze center. Damage to the sixth nerve nucleus or to the caudal paramedian pontine reticular formation produces an ipsilateral gaze palsy that cannot be overcome by vestibular testing.[32] Because all nuclear sixth nerve palsies produce a gaze palsy, an abduction deficit not associated with contralateral adduction weakness cannot arise from nuclear damage.

The location of the sixth nerve nucleus within the brainstem produces several possible associated deficits when a nuclear sixth nerve palsy is present ( Box 198-5 ). As a result of the intimate relationship between the facial nerve fasciculus and the sixth nerve nucleus, an ipsilateral peripheral facial nerve palsy is present in nearly all cases of abducens nuclear injury ( Fig. 198-5 ). The first-order

 

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Figure 198-5 T2-weighted magnetic resonance image of a 33-year-old woman who has a left abduction deficit, gaze paretic nystagmus on left gaze, and left facial weakness. The cause of this nuclear sixth nerve lesion (long arrow) most likely was demyelinating disease. A second lesion can be seen in the right cerebellum (arrowhead).

sympathetic fibers travel in the dorsal pons; damage to these fibers produces an ipsilateral preganglionic Horner’s syndrome. Damage to the trigeminal nucleus and tract produces ipsilateral facial analgesia. Damage to the lateral ventral pons can produce loss of taste. In addition, fibers from the seventh and eighth cranial nerves may be damaged. Foville’s syndrome results from a dorsal pontine infarct (usually from anterior inferior cerebellar artery infarction) and combines an ipsilateral gaze palsy with an ipsilateral facial palsy, loss of taste, and facial analgesia, Horner’s syndrome, and peripheral deafness. It is rare for a patient to have all characteristics of Foville’s syndrome.

When damage from either the sixth nerve nucleus or paramedian pontine reticular formation also involves the ipsilateral medial longitudinal fasciculus, a characteristic motility pattern is produced, consisting of an ipsilateral gaze palsy with an ipsilateral internuclear ophthalmoplegia. The ipsilateral eye cannot adduct or abduct, while the contralateral eye can only abduct. This syndrome is called a one-and-a-half syndrome.[33]

Most nuclear abducens palsies are caused by infarction (anterior inferior cerebellar or paramedian perforating arteries), demyelination, or compression (intrinsic pontine tumors). Infiltrative disease, hemorrhage, and trauma are less likely causative factors (see Box 198-3 ).

Fascicular Sixth Cranial Nerve Palsies

Nearly all fascicular lesions of the abducens nerve are associated with distinctive neurological findings that result from damage to the surrounding neurological structures of the pons. Foville’s syndrome (sixth nerve palsy, ipsilateral Horner’s syndrome, ipsilateral facial analgesia, ipsilateral facial palsy with loss of taste, and ipsilateral peripheral deafness) can occur with either nuclear or fascicular lesions of the sixth nerve. These can be differentiated by evaluation of contralateral adduction: A nuclear lesion has a gaze palsy, while a fascicular lesion has an ipsilateral abduction deficit.

Lesions that affect the abducens fasciculus in the ventral pons can cause a contralateral hemiplegia (Raymond’s syndrome). Millard–Gubler syndrome has ipsilateral peripheral facial weakness in addition to the abduction deficit and contralateral hemiplegia. These eponymous syndromes and their findings are listed in Box 198-5 . Because most lesions can affect both the dorsal and ventral pons, a clinical overlap exists between these syndromes.

Common causes of fascicular lesions include infarction, compression (cerebellar pontine angle tumor or glioma), infiltration, and demyelination, and vary with the age of the patient.[1] [3] [34] Hemorrhage, trauma, and infection are less likely (see Box 198-3 ).

Classic teaching in pediatric ophthalmology held that isolated sixth nerve palsies in childhood should be considered the result of a pontine glioma until proven otherwise. This was based upon a series of 133 such patients seen before 1965 at the Mayo Clinic.[34] Of these children, 52 had tumors, and over 75% of the tumors were pontine gliomas. However, the definition of isolated palsy used in that study meant that no other cranial nerve palsies existed, and not that the remainder of the neurological examination was normal. Most of these children had other abnormalities, such as papilledema and nystagmus. Because children without these associated findings nearly always develop them within a few weeks, a careful neuro-ophthalmologic examination with close follow-up probably is all that is necessary in children (under age 14 years) who have truly isolated idiopathic sixth nerve palsies.

DIAGNOSIS

Palsies of the Third Cranial Nerve

Both nuclear and fascicular third nerve palsies usually can be highly localized on the basis of clinical findings. A detailed examination of ocular motility (see Chapter 197 ) often is sufficient to diagnose nuclear lesions. Particular attention should be paid to vertical gaze abnormalities, because the centers for vertical gaze are in close proximity to the oculomotor nucleus and also are often damaged. Vestibular testing should be performed in patients who have bilateral vertical gaze abnormalities, to differentiate supranuclear from nuclear and infranuclear causes of these disorders. Bell’s reflex often is preserved with supranuclear lesions. A neurological examination should be directed to identify tremor, contralateral hemisensory loss, contralateral hemiplegia, pronator drift, and contralateral hyperreflexia, which help to localize fascicular lesions. Magnetic resonance imaging is the best method by which to assess the integrity of midbrain structures in patients who have acute palsies. The neuroradiologist should be informed of the clinical localization so that attention can be directed to this area.

Palsies of the Fourth Cranial Nerve

Management of fourth nerve palsies depends upon the associated neurological findings and localization. Older adults with an isolated fourth nerve palsy and predisposing factors for vascular disease need only careful follow-up. Imaging studies should be performed if progression occurs, if additional neurological signs develop, or if recovery does not begin to occur within 3 months. Younger individuals who have large fusional amplitudes and photographic documentation of head tilting since infancy or childhood need no further evaluation, because the palsy is likely congenital with recent decompensation. Patients who have acquired fourth nerve palsies with localizing signs should undergo imaging studies, with attention paid to the areas suggested by the clinical findings. Patients who have no risk factors for vascular disease, no history of trauma, and no findings suggestive of a decompensating congenital fourth nerve palsy should undergo imaging studies to rule out small peripheral schwannomas, especially if progression occurs. Inquiry regarding the presence of multiple café-au-lait spots or other stigmata of neurofibromatosis may be useful.

Palsies of the Sixth Cranial Nerve

Management of sixth nerve palsies also depends on the associated findings. All patients who have sixth nerve palsies must receive complete neuro-ophthalmologic evaluation. Specific attention should be paid to the function of the facial nerve and to the other cranial nerves that subserve ocular motility and the pupil. The cerebellum and vestibular system also should be evaluated. Testing of deep tendon reflexes and the peripheral motor system is necessary to rule out corticospinal tract involvement. The optic nerves must be examined to rule out papilledema. Patients who have brainstem findings need magnetic resonance imaging and appropriate management. Patients who have had strokes need immediate neurological

 

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consultation, while patients who have brain tumors need urgent neurosurgical evaluation.

For patients who have truly isolated sixth nerve palsy, nuclear or fascicular involvement is unlikely. The evaluation and work-up of these patients is given in detail in Chapter 199 . However, it should be remembered that all abduction deficits are not the result of sixth nerve palsies—myasthenia, thyroid disease, Duane’s syndrome, and orbital disorders must be ruled out.

TREATMENT, COURSE, AND OUTCOME

Palsies of the Third Cranial Nerve

Many patients who have ischemic oculomotor nerve palsies eventually improve. Ptosis is often advantageous in this situation, because it prevents diplopia. Strabismus correction and lid surgery are needed to restore binocularity in patients who do not improve spontaneously; the author waits for stable measurements to occur for 6 months before suggesting surgical alignment. Specific techniques for restoring motility in patients who have third nerve palsy (superior oblique tendon transfer) are discussed elsewhere.[35]

Palsies of the Fourth Cranial Nerve

Palsies of the fourth nerve that result from vascular disease or trauma often resolve spontaneously over 3–6 months. During this time, Fresnel prisms can be placed over spectacles to allow fusion. However, this often is fraught with difficulty, because the deviation is usually quite incomitant and torsion cannot be corrected. Patients who have fourth nerve palsies that arise from compressive lesions often do not improve and require surgery.

Surgical options for the treatment of superior oblique palsy are complex and are beyond the scope of this chapter. The choice of procedure depends upon the deviation in primary position, the deviation in the fields of action of the paretic superior oblique and the antagonist inferior oblique, the deviation out of the field of action of the involved superior oblique, and the objective and subjective torsion. Knapp[36] and Scott and Kraft[37] [38] have proposed surgical classification schemes; this author prefers that of Scott because it is more detailed and has better long-term follow-up. Congenital superior oblique palsies often are associated with abnormalities of the insertion of the superior oblique tendon and have been discussed by Wallace and von Noorden.[39]

Palsies of the Sixth Cranial Nerve

Nearly all patients who have sixth nerve palsies experience diplopia. During the acute phase, this is best managed by patching the paretic eye or by frosting a spectacle lens. Prisms usually are not tolerated well because of the magnitude and incomitance of the deviation. Botulinum toxin has been suggested to prevent secondary contracture of the antagonist medial rectus for patients who have acute bilateral sixth nerve palsies (trauma). Injection of the ipsilateral medial rectus muscle with 5 units of botulinum toxin (Botox) often weakens this muscle sufficiently to allow fusion with a small face turn while recovery of lateral rectus function occurs.[40] Botulinum toxin injection probably does not decrease the need for later surgical intervention of unilateral sixth nerve palsy.[41] [42]

Surgical intervention for sixth nerve palsy is indicated when the deviation has been stable for a minimum of 6 months. Preoperative evaluation should include determination of corneal sensation and lid closure; patients who have constant esodeviations often are protected from exposure keratopathy by the relative position of the eye and can experience severe corneal damage if the eye is brought to primary position when lagophthalmos or hypesthesia is present. The choice of surgical procedure for chronic sixth nerve palsies depends upon the recovery of function of the lateral rectus muscle, which can be assessed by determining the saccadic velocity. Patients who have good return of function usually do quite well with an ipsilateral recess–resect procedure. Patients who have little or no lateral rectus function need muscle transposition surgery. The transposition procedure described by Jensen works well to restore binocularity, with little risk of anterior segment ischemia. [43] Other transposition procedures have been described, but fewer long-term follow-up data are published.

 

 

REFERENCES

 

1. Rush JA, Younge BR. Paralysis of cranial nerves III, IV, and VI. Cause and prognosis in 1000 cases. Arch Ophthalmol. 1981;99:76–9.

 

2. Berlit P. Isolated and combined pareses of cranial nerves III, IV, and VI. A retrospective study of 412 patients. J Neurol Sci. 1991;103:10–5.

 

3. Richards BW, Jones FR Jr, Younge BR. Causes and prognosis in 4278 cases of paralysis of the oculomotor, trochlear, and abducens cranial nerves. Am J Ophthalmol. 1992;113:489–96.

 

4. Kodsi SR, Younge BR. Acquired oculomotor, trochlear, and abducent cranial nerve palsies in pediatric patients. Am J Ophthalmol. 1992;114:568–74.

 

5. Miller NR. Topical diagnosis of neuropathic ocular motility disorders. In: Miller NR, ed. Walsh & Hoyt’s clinical neuro-ophthalmology, ed 4. Baltimore: Williams & Wilkins, 1985:652–784.

 

6. Balkan R, Hoyt CS. Associated neurologic abnormalities in congenital third nerve palsies. Am J Ophthalmol. 1984;97:315–9.

 

7. Hamed LM. Associated neurologic and ophthalmologic findings in congenital oculomotor nerve palsy. Ophthalmology. 1991;98:708–14.

 

8. Good WV, Barkovich AJ, Nickel BL, Hoyt CS. Bilateral congenital oculomotor nerve palsy in a child with brain anomalies. Am J Ophthalmol. 1991;111:555–8.

 

9. Warwick R. Representation of the extraocular muscles in the oculomotor nuclei of the monkey. J Comp Neurol. 1953;98:449–503.

 

10. Daroff RB. Oculomotor manifestation of brainstem and cerebellar dysfunction. In: Smith JL, ed. Neuro-ophthalmology: symposium of the University of Miami and Bascom-Palmer Eye Institute, vol 5. Hallandale: Huffman; 1971:104–21.

 

11. Bryan JS, Hamed LM. Levator-sparing nuclear oculomotor palsy. Clinical and magnetic resonance imaging findings. J Clin Neuroophthalmol. 1992;12:26–30.

 

12. Martin TJ, Corbett JJ, Babidian PV, et al. Bilateral ptosis due to mesencephalic lesions with relative preservation of ocular motility. J Neuroophthalmol. 1996; 16:258–63.

 

13. Pratt DV, Orengo-Nania S, Horowitz BL, Oram O. Magnetic resonance imaging findings in a patient with nuclear oculomotor palsy. Arch Ophthalmol. 1995; 113:141–2.

 

14. Barton JJ, Kardon RH, Slagel D, Thompson HS. Bilateral central ptosis in acquired immunodeficiency syndrome. Can J Neurol Sci. 1995;22:52–5.

 

15. Keane JR, Zaias B, Itabashi HH. Levator-sparing oculomotor nerve palsy caused by a solitary midbrain metastasis. Arch Neurol. 1984;41:210–2.

 

16. Warren W, Burde RM, Klingele TG, Roper-Hall G. Atypical oculomotor paresis. J Clin Neuroophthalmol. 1982;2:13–8.

 

17. Ksiazek SM, Slamovits TL, Rosen CE, et al. Fascicular arrangement in partial oculomotor paresis. Am J Ophthalmol. 1994;118:97–103.

 

18. Ksiazek SM, Repka MX, Maguire A, et al. Divisional oculomotor nerve paresis caused by intrinsic brainstem disease. Ann Neurol. 1989;26:714–8.

 

19. Breen LA, Hopf HC, Farris BK, Gutmann L. Pupil-sparing oculomotor nerve palsy due to midbrain infarction. Arch Neurol. 1991;48:105–6.

 

20. Fleet WS, Rapcsak SZ, Huntley WW, Watson RT. Pupil-sparing oculomotor palsy from midbrain hemorrhage. Ann Ophthalmol. 1988;20:345–6.

 

21. Hopf HC, Gutmann L. Diabetic 3rd nerve palsy: evidence for a mesencephalic lesion. Neurology. 1990;40:1041–5.

 

22. Norman MG. Unilateral encephalomalacia in cranial nerve nuclei in neonates. Report of two cases. Neurology. 1974;24:424–7.

 

23. Victor DI. The diagnosis of congenital unilateral third-nerve palsy. Brain. 1976; 99:711–8.

 

24. Loewenfeld IE, Thompson HS. Oculomotor paresis with cyclic spasms. A critical review of the literature and a new case. Surv Ophthalmol. 1975;20:81–124.

 

25. von Noorden GK, Murray E, Wong SY. Superior oblique paralysis. Arch Ophthalmol. 1986;104:1771–6.

 

26. Brazis PW. Palsies of the trochlear nerve: diagnosis and localization—recent concepts. Mayo Clin Proc. 1993;68:501–9.

 

27. Keane JR. Fourth nerve palsy: historical review and study of 215 inpatients. Neurology. 1993;43:2439–43.

 

28. Guy J, Day AL, Mickle JP, Schatz NJ. Contralateral trochlear nerve paresis and ipsilateral Horner’s syndrome. Am J Ophthalmol. 1989;107:73–6.

 

29. Tachibana H, Minura O, Shiomi M, Oono T. Bilateral trochlear nerve palsies from a brainstem hematoma. J Clin Neuroophthalmol. 1990;10:35–7.

 

30. Eliott D, Cunningham ET Jr, Miller NR. Fourth nerve paresis and ipsilateral relative afferent pupillary defect without visual sensory disturbance. J Clin Neuroophthalmol. 1991;11:169–72.

 

31. Slavin ML. Hyperdeviation associated with isolated unilateral abducens palsy. Ophthalmology. 1989;96:512–6.

 

32. Muri RM, Chermann JF, Cohen L, et al. Ocular motor consequences of damage to the abducens nucleus area in humans. J Neuroophthalmol. 1996;16:191–5.

 

33. Wall M, Wray SH. The one-and-a-half syndrome—a unilateral disorder of the pontine tegmentum: a study of 20 cases and review of the literature. Neurology. 1983;33:971–80.

 

34. Robertson DM, Hines JD, Rucker CW. Acquired sixth nerve paresis in children. Arch Ophthalmol. 1970;83:574–9.

 

35. van Noorden GK, Campos EC. Binocular vision and ocular motility, 6th ed. St Louis: Mosby; 2002.

 

36. Knapp P. Classification and treatment of superior oblique palsy. Am Orthopt J. 1974;24:18–22.

 

37. Scott WE, Kraft SP. Classification and surgical treatment of superior oblique palsies: I. Unilateral superior oblique palsies. In: New Orleans Academy of Ophthalmology. Pediatric ophthalmology and strabismus: transactions of the New Orleans Academy of Ophthalmology. New York: Raven Press; 1986:15–38.

 

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38. Scott WE, Kraft SP. Classification and treatment of superior oblique palsies: II. Bilateral superior oblique palsies. In: New Orleans Academy of Ophthalmology. Pediatric ophthalmology and strabismus: transactions of the New Orleans Academy of Ophthalmology. New York: Raven Press; 1986:265–91.

 

39. Wallace DK, von Noorden GK. Clinical characteristics and surgical management of congenital absence of the superior oblique tendon. Am J Ophthalmol. 1994;118:63–9.

 

40. Repka MX, Lam GC, Morrison NA. The efficacy of botulinum neurotoxin A for the treatment of complete and partially recovered chronic sixth nerve palsy. J Pediatr Ophthalmol Strabismus. 1994;31:79–83.

 

41. Lee J, Harris S, Cohen J, et al. Results of a prospective randomized trial of botulinum toxin therapy in acute unilateral sixth nerve palsy. J Pediatr Ophthalmol Strabismus. 1994;31:283–6.

 

42. Archer S. Study needs more statistical power. J Pediatr Ophthalmol Strabismus. 1995;32:142.

 

43. Cline RA, Scott WE. Long-term follow-up of Jensen procedures. J Pediatr Ophthalmol Strabismus. 1988;25:264–9.

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4 comments on “Chapter 198 – Nuclear and Fascicular Disorders of Eye Movement

  1. Your post caught my eye. Thanks for offering this information.

  2. All ’round amazingly written blog post.

  3. Nice post, but will anyone tell me how to get the figures; I am able to see the legends but not the figures

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