Journal of Binocular Vision and Ocular Motility

ISSN: 2576-117X (Print) 2576-1218 (Online) Journal homepage: http://www.tandfonline.com/loi/uaoj21

Isolated Ocular Motor Nerve Palsies

Stacy L. Pineles & Federico G. Velez

To cite this article: Stacy L. Pineles & Federico G. Velez (2018): Isolated Ocular Motor Nerve
Palsies, Journal of Binocular Vision and Ocular Motility, DOI: 10.1080/2576117X.2018.1481266

To link to this article: https://doi.org/10.1080/2576117X.2018.1481266

Published online: 21 Jun 2018.

Submit your article to this journal

Article views: 3

View Crossmark data

Full Terms & Conditions of access and use can be found at

http://www.tandfonline.com/action/journalInformation?journalCode=uaoj21
JOURNAL OF BINOCULAR VISION AND OCULAR MOTILITY
https://doi.org/10.1080/2576117X.2018.1481266

EVERYTHING YOU NEED TO KNOW IN 2018 ABOUT:

Isolated Ocular Motor Nerve Palsies

Stacy L. Pineles, M.D., M.S. and Federico G. Velez, M.D.
Department of Ophthalmology, University of California Los Angeles, Los Angeles, California

ABSTRACT ARTICLE HISTORY

Isolated cranial nerve (CN) palsies are frequently encountered by strabismologists. Management Received 18 April 2018
decisions for patients with isolated ocular motor nerve palsies must take into account multiple Accepted 11 May 2018
factors, including patient age, historical features, the specific CN affected, examination findings, KEYWORDS
and coexistent medical diagnoses. In general, isolated ocular motor nerve palsies in children are Strabismus; diplopia; cranial
assessed and managed differently than adults. Furthermore, older adults with vascular risk factors nerve palsy
may be managed differently than younger adults and children. The need for urgent neuroimaging
in older adults with microvascular risk factors is under debate and requires the physician to weigh
the risks and benefits of close observation with immediate testing. The presence of multiple
cranial neuropathies should also raise the level of concern and indicate the need for a more
urgent work-up. The following manuscript aims to provide information on common etiologies of
isolated ocular motor nerve palsies and to suggest algorithms for the management of these CN
palsies in children and adult.

Isolated cranial nerve (CN) palsies present a difficult muscle. Interestingly, the superior rectus subnucleus
scenario for physicians who examine both children and innervates the contralateral superior rectus muscle,
adults with strabismus. Decisions regarding work-up while the remainder of the subnuclei innervate the
and management can be challenging and depend in ipsilateral corresponding muscles. The Edinger-
part on patient characteristics, historical features, and Westphal nucleus, which supplies innervation to the
examination findings. The purpose of this manuscript pupillary sphincter, is shared by both sides. The oculo-
is to provide up-to-date information for strabismus motor nerve fascicle exits the brainstem through the
specialists on isolated ocular motor palsies in children ventral midbrain in the interpeduncular fossa.
and adults, outlining common etiologies (Table 1) and The trochlear nerve nucleus is located in the ventral
suggested algorithms for work-up (Table 2). pontomesencephalic junction caudal to the oculomotor
nuclei. The trochlear nerve fascicles decussate to inner-
vate the contralateral superior oblique muscle, and exit
Review of cranial nerve anatomy
the brainstem dorsally beneath the inferior colliculi.
The three ocular motor nerves innervate the six extraocular The abducens nucleus resides in the dorsal pons. The
muscles as well as the levator palpebrae superioris (LPS) abducens nerve fascicles travel ventrally and exit the
and the pupillary sphincter. The oculomotor nerve (CNIII) brainstem at the pontomedullary junction to innervate
innervates the LPS, superior rectus, inferior rectus, medial the ipsilateral lateral rectus muscle.
rectus, inferior oblique, and the pupillary sphincter. The All three ocular motor nerves travel through the subar-
trochlear nerve (CNIV) innervates the superior oblique achnoid space at the skull base and into the cavernous
muscle, and the abducens nerve (CNVI) innervates the sinus. Within the cavernous sinus, they are adjacent to
lateral rectus muscle. The pathways involved in supranuc- the first and second division of the trigeminal nerve, the
lear control of the ocular motor nerves descend from the internal carotid artery, and the third-order oculosympa-
cerebral cortex and terminate in the brainstem in the thetic fibers. In the cavernous sinus, the oculomotor nerve
omipause neurons (for horizontal saccades) and the rostral divides into superior and inferior divisions which innervate
interstitial nucleus of the medial longitudinal fasciculus of the (1) superior rectus and LPS and (2) the inferior rectus,
the midbrain (for vertical saccades). inferior oblique, medial rectus, and pupillary sphincter,
The oculomotor nucleus resides in the midbrain and respectively. The nerves then exit the cavernous sinus and
is divided into individual subnuclei for each extraocular traverse the orbit. CNIII and CNVI are positioned within

CONTACT Stacy L. Pineles pineles@jsei.ucla.edu Department of Ophthalmology, University of California Los Angeles, 100 Stein Plaza, Los Angeles,
CA 90095.
© 2018 American Orthoptic Journal Inc.
2 S. L. PINELES AND F. G. VELEZ

Table 1. Common etiologies of isolated ocular motor nerve palsy.

Age
group Oculomotor nerve Trochlear nerve Abducens nerve
Pediatric ● Congenital ● Congenital ● Neoplasm
● Traumatic ● Traumatic
● Neoplastic ● Craniofacial anomalies ○ Medulloblastoma, ependymoma,
● Neoplastic pontine glioma
○ Midbrain astrocytoma, glioma, orbital
rhabdomyosarcoma ○ Astrocytoma, glioma ● Trauma
○ Intrinsic nerve tumors (especially in ○ Intrinsic nerve tumors (especially in ● Meningitis
neurofibromatosis) neurofibromatosis)
● Meningitis ○ Pneumococcus
● Meningitis ○ Haemophilus influenza
○ Pneumococcus ○ Tuberculosis
○ Haemophilus influenza ○ Pneumococcus ○ Lyme
○ Tuberculosis ○ Haemophilus influenza ● Benign abducens palsy
○ Lyme ○ Tuberculosis
● Migraine ○ Lyme

Adult Microvascular ischemia Congenital Neoplasm

Stroke Trauma Trauma
Aneurysm Microvascular ischemia Microvascular ischemia
Traumatic Stroke Stroke

Table 2. Suggested work-up for patients with isolated ocular motor nerve palsies.
Age
group Oculomotor nerve Trochlear nerve Abducens nerve
Pediatric Congenital: contrast-enhanced MRI of the brain and Congenital: no work-up required Congenital: consider Duane
orbits syndrome and Moebius syndrome

Acquired: Acquired: Acquired:

● Contrast-enhanced MRI brain/orbits ● Contrast-enhanced MRI brain/orbits ● Contrast-enhanced MRI brain/
● MR-angiography (to exclude vascular lesions) ● Consider lumbar puncture if symptoms of orbits
● Consider lumbar puncture if normal neuroimaging meningitis ● Serologies: syphilis, Lyme
● Consider migraine if normal lumbar puncture ● Consider lumbar puncture if
● In older children (>10), consider conventional symptoms of meningitis or
angiography if all testing normal (to exclude pos- elevated intracranial pressure
terior communicating artery aneurysm)

Adult ● Evaluate for undiagnosed vascular risk factors ● Evaluate for undiagnosed vascular risk factors ● Evaluate for undiagnosed
● Contrast-enhanced MRI brain and orbits – if elderly and +vascular risk factors, it is vascular risk factors
● MRA or CTA brain reasonable to observe for resolution ● Serologies: syphilis, Lyme
● If high suspicion and normal MRA/CTA, consider ● Contrast-enhanced MRI of the brain and orbits ● Contrast-enhanced MRI of the
conventional angiography ● Consider lumbar puncture if symptoms of brain and orbits
● If imaging normal, consider lumbar puncture meningitis ● Consider lumbar puncture if
● If all studies normal, evaluate for mimics ● Evaluate for mimics (myasthenia gravis, thyr- symptoms of meningitis
(myasthenia gravis, thyroid, GCA) oid, GCA) ● Evaluate for mimics (myasthe-
nia gravis, thyroid, GCA)

GCA = giant cell arteritis.

the annulus of Zinn, while CNIV lies outside of the annulus pediatric versus adult onset. Congenital CNIII palsies are
of Zinn. In-depth knowledge of the pathways of the ocular often noted soon after birth due to the obvious nature of
motor nerves as well as adjacent structures provides clin- their presentation. However, congenital CNIV and CNVI
icians with the knowledge required to understand various palsies are often not noticed until the child begins to track
clinical presentations of CN palsies with coexistent neuro- objects and gain head control, which allows the patient to
logical syndromes. adopt an anomalous head posture to facilitate fusion. In
order to determine whether a CN palsy is congenital in
nature, physicians must review old photographs and elicit
Isolated cranial nerve palsies in children versus
findings on the examination such as aberrant regenera-
adults
tion, which may be seen in congenital CNIII palsies as
The details of presentation and management of isolated well as several other etiologies. Furthermore, while con-
ocular motor nerve palsies will be discussed in the forth- genital CNIII and CNIV palsies are relatively common
coming sections. However, there are some general con- (CNIV more than CNIII), it is exceedingly rare to see a
cepts that apply to any type of CN palsy with respect to congenital CNVI palsy without Duane syndrome or
 JOURNAL OF BINOCULAR VISION AND OCULAR MOTILITY 3

Moebius syndrome. Non-congenital childhood onset CN studies using modern neuroimaging techniques appear
palsies are often difficult to characterize based on the to conflict, and the same data have been interpreted for
difficulty of history-taking and examination in young either recommendation and used both in pro and con
children. Frequently, head trauma may be unobserved arguments. In 2004, a prospective study of 66 patients
or unreported. Additionally, symptoms such as headache, over the age of 50 years with isolated ocular motor
diplopia, nausea, weakness, or numbness may not be neuropathies who underwent neuroimaging found that
elicited as easily in pediatric patients compared to adults. 14% of patients had positive findings, and the authors
Lastly, adult patients may be more likely to observe and therefore recommended imaging of these patients upon
report variability of their symptoms throughout the day presentation. However, in a retrospective epidemiological
than children. study, Patel et al. failed to find an indication for acute
In terms of underlying etiologies to consider, the most imaging of older adults and elderly patients with isolated
common causative factors are also different among pedia- acute abducens palsy.3 Later, this controversy was further
tric and adult patients. In pediatric patients, the most intensified by two prospective studies that also reported
common presenting etiologies overall include congenital differing conclusions. A 2011 study focusing mainly on
malformations, brainstem or posterior fossa neoplasms, cost analysis evaluated patients over the age of 50 years
inflammatory conditions, and migraine. Also possible in with isolated cranial mononeuropathies and found that
children is congenital absence of the CN or muscle.1 In only one (2%) patient had an abnormal MRI (a pontine
adults, vascular etiologies such as aneurysm and micro- hemorrhage). The authors modeled the total cost for
vascular ischemia are often foremost in the differential imaging in the study to be $131,688 to find only one
diagnosis. Diabetes mellitus should always be considered lesion and therefore argued that imaging in this circum-
in cases of isolated cranial neuropathies in adults. stance should be reserved for those cases who fail to
Demyelination, trauma, tumors, and increased intracra- resolve after 3 months or for patients who are less than
nial pressure can be considered in any age groups. 50 years of age, have a history of cancer, or if the cranial
neuropathy is not isolated.4 Conversely, in 2013,
Tamhankar and colleagues5 prospectively evaluated neu-
Isolated ocular motor nerve palsies in older
roimaging findings in 109 patients from with isolated
adults with vascular risk factors
cranial neuropathy several centers. In this study, 10% of
Although each type of ocular motor neuropathy will be patients with vascular risk factors had abnormal work-
discussed in detail, there is one encompassing concept ups, which included neoplasms, giant cell arteritis, and
that is shared by all of them with regard to presentation brainstem infarcts. This paper argued for urgent neuroi-
in older adults. There is great debate in the literature maging of all cases, even those in which a microvascular
regarding the management of older adults and elderly etiology is likely. Given this level of controversy and the
patients with an isolated cranial neuropathy and known reasonable arguments on both sides, the decision to work
vascular risk factors.2 Classic teaching has generally been up an isolated ocular motor nerve palsy in an older adult
that it is safe to carefully observe older adults and elderly or elderly patient with known vascular risk factors must
patients with vascular risk factors who have a truly iso- be based upon the clinician and patient values and level
lated ocular motor neuropathy for improvement, given of concern, which can be founded upon the clinician’s
the high likelihood of a microvascular insult. Historical own comfort level with the patient’s age, risk factors, and
recommendations were only to work up the cranial neu- access to imaging, as well as their ability to comply with
ropathy if there is no improvement after 3 months. This very close follow-up.
standpoint is rooted both in an earlier era of neuroima-
ging at which time the sensitivity of MRI was not as high
Isolated oculomotor nerve palsy
as it is in modern times and importantly in consideration
of cost-effectiveness, for which many studies have shown The presentation of an isolated CNIII palsy can vary from
that imaging all of these patients has a very low yield of a complete palsy with the characteristic ptosis, mydriasis
management-changing outcomes. However, in the past and “down and out” appearance of the affected eye to a
decade, many clinicians have worked to change this milder form, with any combination of affected muscles
recommendation, given the higher quality of neuroima- and any level of severity. When considering a CNIII palsy,
ging and the advent of new treatments for strokes, brain a distinction is often made between a “complete” and
tumors, and vascular anomalies. There are reasonable “incomplete” palsy. A complete palsy is diagnosed when
arguments on both sides of this debate, and the recom- there is complete ptosis, a fixed pupil, and complete
mendations may vary based upon which of the three paralysis of the superior rectus, inferior rectus, inferior
ocular motor nerves is involved.2 Data from research oblique, and medial rectus. Historically, this distinction
4 S. L. PINELES AND F. G. VELEZ

was thought to reflect the anatomical location of the consciousness, evolution of the CNIII involvement, and
causative lesion; however, it is now established that hemiplegia will result. Similarly, posterior communicat-
incomplete palsies can result from lesions anywhere ing artery aneurysms in adults typically result in an early
along the pathway of the nerve. CNIII palsy with prominent mydriasis, but the most
When examining a patient with a suspected CNIII common accompanying symptom is pain. A common
palsy, it is important to determine which muscles are misconception is that posterior communicating artery
affected in order to define whether the palsy may be aneurysm should only be considered in cases with
divisional (superior vs. inferior). Divisional palsies are mydriasis; however, pupillary sparing may occur in up
typically attributed to lesions in the pathway anterior to to 14% of CNIII palsies attributed to aneurysm.12 Other
or within the cavernous sinus, although they have also types of aneurysms that may result in CNIII compression
been localized as far posteriorly as the nerve fascicle or include basilar artery and internal carotid aneurysms.
subarachnoid space.6–9 Evidence of aberrant regeneration Within the subarachnoid space, children and adults may
should also be sought as it is considered extremely rare in also develop primary tumors of the nerves such as neu-
ischemic etiologies and its presence in a non-congenital romas and schwannomas. These tumors can present at
or nontraumatic case should prompt practitioners to any age and typically result in a slowly progressive CNIII
evaluate for a compressive lesion.10 palsy without coexistent symptoms. Skull base tumors
Given the anatomy of the third nerve, there are several such as meningiomas or chordomas may also compress
coexistent symptoms that should be sought on history CNIII in this location.
and examination in order to localize the lesion and In the cavernous sinus, oculomotor nerve palsies are
guide work-up. Lesions of the oculomotor nucleus can rarely isolated. They typically occur in conjunction with
result in bilateral ptosis (due to a shared LPS nucleus), CNIV or CNVI dysfunction, as well as evidence of tri-
contralateral or bilateral SR palsy (due to the crossing geminal involvement or Horner syndrome. Interestingly,
fibers of the SR nucleus), ipsilateral mydriasis and ipsilat- due to the proximity of the oculosympathetic fibers, one
eral inferior rectus, medial rectus, and inferior oblique can find an absence of mydriasis in patients with CNIII
palsies. Although this clinical scenario is fairly classic for a palsy due to cavernous sinus lesions when both the para-
nuclear lesion, there is variability in the possible presenta- sympathetic and sympathetic fibers are equally affected.
tion, and a nuclear third nerve palsy may also be Lesions to consider in the cavernous sinus include neo-
mimicked by a fascicular lesion.11 Fascicular CNIII palsies plasms, cavernous sinus thrombosis, infectious etiologies,
are often associated with obvious neurological symptoms and high or low flow carotid-cavernous fistulas.
due to the adjacent structures in the brainstem. In chil-
dren and adults with CNIII palsies, the following symp-
When should one pursue further work-up in
toms should be sought to evaluate for brainstem
patients with isolated oculomotor nerve
syndromes: contralateral ataxia (Claude syndrome), con-
dysfunction?
tralateral hemiparesis (Weber syndrome), and contralat-
eral tremor (Benedikt syndrome). Despite the proximal Whether all patients with CNIII palsies require further
location, fascicular CNIII palsies can present with super- work-up and neuroimaging is a debated topic among
ior or inferior divisional involvement given the topogra- neuro-ophthalmologists. The majority of clinicians agree
phical arrangement of the nerve fibers. Rarely, nuclear that all CNIII palsies require further work-up; however, the
and fascicular lesions can result in an isolated muscle two entities that are not pursued by some practitioners are
palsy, although isolated muscle palsies should also prompt congenital CNIII palsies and presumed vasculopathic
consideration of other diagnostic entities. CNIII palsies (“pupil-sparing complete palsies”).
In the subarachnoid space, the oculomotor nerve is Although in adults over the age of 50 years with an isolated
susceptible to compression, which may be a sign of a complete “pupil-sparing” CNIII palsy some clinicians feel
life-threatening condition. Uncal herniation can result in comfortable observing for resolution within 3 months if
a third nerve palsy with altered mental status in a patient there are coexistent vascular risk factors, the majority of
of any age, although compression of the third nerve by a neuro-ophthalmologists agree that even patients with these
posterior cerebral artery aneurysm is much more com- “pupil-sparing” CNIII palsies should undergo neuroima-
mon in adults than pediatric patients. Due to the dor- ging at the time of presentation due to the possibility of
somedial location of the pupillary fibers in the CNIII missing a small infarct or mass lesion.13–15 Certainly if
bundle, mydriasis is often the first sign of CNIII compres- there is no resolution of a presumed microvascular third
sion in the subarachnoid space. Adults and children with nerve palsy, or if the patient is younger than 50 years of age
uncal herniation may initially present with pupillary dila- or has no vascular risk factors, then these patients should all
tion, but as the syndrome progresses, decreased undergo urgent work-up. Diabetes mellitus should also be
 JOURNAL OF BINOCULAR VISION AND OCULAR MOTILITY 5

considered in these cases and tested for as part of the initial When examining a patient with a suspected CNIV
work-up. Although rare, patients with diabetes can also palsy, it is important to determine whether the symptoms
present with an aneurysm. are acute in onset or whether they are long-standing and
In children with CNIII palsy, it is estimated that potentially congenital. Patients with congenital trochlear
18–47% of cases are of congenital origin.16 Congenital palsies frequently present with a head tilt that can be seen
palsies classically have pupillary involvement and aber- in childhood photographs, large fusional amplitudes, and
rant regeneration. Congenital palsies have been attributed facial asymmetry. If these historical and examination fea-
to abnormalities anywhere along the pathway of the nerve tures can be proven, then further work-up is not required.
from the nucleus to the peripheral bundle. As neuroima- However, in acute cases or those in which the history is
ging techniques improve, it has become evident that some unclear, further consideration must be given.
congenital palsies are in actuality secondary to neuromas Due to the anatomical course of the fourth nerve,
or schwannoma.17 For all other patients presenting with trauma is the most common cause of acquired palsies in
chronic (non-congenital) or acute third nerve palsies, children and adults.20–23 Trauma frequently causes unilat-
further work-up is mandated. eral or bilateral trochlear palsies due to the long path of the
For adult patients with acute third nerve palsies who nerves and their close proximity between the decussating
are being referred for urgent imaging to rule out a life- nerve fibers and the tentorium, which can create contu-
threatening aneurysm, computed tomography (CT) or sions or pressure on the nerves. In the absence of trauma,
MRI angiography should be performed in conjunction additional diagnoses to consider vary based on the age of
with radiology consultation to evaluate for the presence of the patient. In adults, microvascular ischemia to the tro-
an aneurysm. If the CT angiogram or MR angiogram is chlear nerve may cause an acute palsy that improves over
normal but suspicion is high for an aneurysm, then con- time. Vascular risk factors including age over 50 years,
ventional angiography should be considered. For adult diabetes, hypertension, and hypercholesterolemia may
patients without an aneurysm and for all pediatric indicate a high likelihood of a microvascular etiology in
patients, a high-quality contrast-enhanced MRI should an older patient with an acute CNIV palsy; however, simi-
be performed of the brain and orbits. MRI should also larly to patients with presumed microvascular oculomotor
be considered in patients with traumatic third nerve palsy palsies, there is a risk of missing a neoplasm, brainstem
due to the possibility of pseudoaneurysm, orbital fracture, stroke, or demyelination if no further work-up is consid-
or cavernous sinus fistula. In adults and patients with ered. Therefore, it is reasonable in adults, even in cases of
acute CNIII palsy and normal neuroimaging, limited presumed microvascular insult to at least consider neuroi-
laboratory work-up should be considered and guided by maging, especially if there is no resolution of the palsy after
the clinical scenario: testing might include cholesterol 3 months. Other diagnoses that can be considered in
levels, blood pressure measurement, glucose levels, thyr- certain circumstances include neoplasms, meningitis, mid-
oid function tests, testing for myasthenia gravis, or a brain hemorrhage or stroke, giant cell arteritis, schwanno-
lumbar puncture with analysis for various infectious and mas, and neurinomas.16 In children, other relatively
inflammatory conditions. An ophthalmoplegic migraine, common causes include craniofacial anomalies, hydroce-
which presents more frequently in children, is considered phalus, tumors, and orbital inflammation.24
a diagnosis of exclusion.18,19
When should one pursue further work-up in
patients with isolated trochlear nerve dysfunction?
Isolated trochlear nerve palsy
In children and adults, if the history and examination are
The presentation of an isolated CNIV palsy can vary consistent with a congenital origin, then no further work-
depending on the severity and the age at onset. In patients up is required. However, in adults with an acute onset of
with a congenital or very early onset trochlear palsy, there diplopia, further work-up should always be considered. In
may be no manifest hypertropia, as these patients often cases that a microvascular etiology is likely, there is still
develop large fusional amplitudes. In these cases, patients debate as to whether immediate versus delayed neuroi-
more typically present with torticollis or complaints of maging should be considered. Some clinicians feel that it
intermittent diplopia or asthenopia; a prolonged cover is reasonable to wait 3 months to determine whether the
testing or a patch test may be required in order for the palsy will resolve on its own (thereby indicating a likely
practitioner to discover the hypertropia. Conversely, acute microvascular ischemic etiology) while others recom-
acquired trochlear palsies more typically present with a mend earlier neuroimaging due to the risk of missing an
larger manifest hypertropia, abnormal ductions, and con- occult mass or ischemic lesion. In the most recent pro-
stant cyclovertical diplopia. spective study by Tamhankar et al., 12% of patients with
6 S. L. PINELES AND F. G. VELEZ

an isolated CNIV mononeuropathy over the age of 50 Other diagnoses that can be considered in adults
years had abnormal work-ups, including one patient who include hemorrhage, stroke, neoplasm, meningitis,
also had vascular risk factors but was found to have a new intracranial hypertension, and giant cell arteritis. In
dorsal midbrain infarct.5 However, other population- children, the most common causes include trauma,
based studies have failed to show a benefit to neuroima- brain neoplasms, elevated intracranial pressure, and
ging in these cases and it is therefore still debatable meningitis.20,22,23,28–31 Although benign recurrent
whether it is required.25 Of the three types of ocular sixth nerve palsy and post-vaccination sixth nerve
motor neuropathies, neuroimaging has the lowest yield palsy are also relatively common in children, these
in trochlear nerve palsies and therefore observation in should be diagnoses of exclusion, after a complete
cases that are presumed microvascular is very reasonable.2 work-up has been done.
In all other adults and children who do not have a con-
genital onset or vascular risk factors, an MRI should be
When should one pursue further work-up in
considered with special attention to the midbrain, caver-
patients with isolated abducens nerve dysfunction?
nous sinus, and orbit. If there are any signs of meningitis,
a lumbar puncture should also be considered. If neuroi- Similar to the other ocular motor nerve palsies, it is still
maging is normal, then other diagnoses such as thyroid debated whether further work-up is required in older adults
eye disease and myasthenia gravis should be considered and elderly patients with an abducens palsy who have
and worked up if indicated. known vascular risk factors. In Chou et al.’s study from
2004, 17% of older adult patients with isolated abducens
palsies had positive neuroimaging findings.13 Similarly, in
Tamhankar et al.’s study 19% of patients with an abducens
Isolated abducens nerve palsy
palsy who were prospectively evaluated with neuroimaging
The presentation of an isolated CNVI palsy can vary were found to have an abnormal work-up, with diagnoses
depending on the severity of the paralysis. Patients may that included cavernous sinus lymphoma, petroclival
present with a small esotropia and face turn, or a large meningioma, and giant cell arteritis.5 However, Patel et al.
esotropia that precludes fusion in any direction of gaze. in a retrospective study of the Olmstead County,
Due to the anatomical course of the sixth nerve, several Minnesota, database failed to identify any cases of neoplasm
associated symptoms must be sought in order to localize or aneurysm that did not present with coexisting historical
the lesion. Neurons reside in the sixth nerve nucleus that and examination features of an additional neurologic
is destined to ascend within the medial longitudinal fas- symptom or sign.3 Given the findings of the two former
ciculus to innervate the contralateral medial rectus muscle papers, many clinicians typically work up patients with
for ipsilateral gaze. For this reason, a nuclear abducens neuroimaging even if they have a likely microvascular
palsy is typically associated with a gaze palsy in the ipsi- etiology since an isolated sixth nerve palsy can be poten-
lateral direction. In addition, nuclear abducens palsies are tially more dangerous than a fourth nerve palsy as it can
also almost always associated with facial nerve palsies due indicate a clival or cavernous sinus lesion, or increased
to the proximity of the facial nerve nucleus and genu. As intracranial pressure. However, an equally convincing
the sixth nerve traverses the petrous apex, it can be argument could be made for a “watch and wait” approach
affected by intracranial pressure changes as well as by based on the study of Patel and colleagues.3 This decision
skull base tumors. In the cavernous sinus, the oculosym- can generally be based upon the clinician/patient values and
pathetic fibers are adjacent to the abducens nerve and level of concern, as well as the patient’s ability to comply
therefore a coexistent Horner syndrome must be sought. with very close follow-up if no imaging is obtained initially.
Abducens palsies are the most common isolated ocular For all other cases, a contrast-enhanced MRI of the
motor cranial neuropathy.26,27 In adults, the most frequent brain and orbits should be obtained. Furthermore, lumbar
etiologies include trauma and microvascular ischemia. puncture can be considered in patients with a normal brain
Vascular risk factors indicate a high likelihood of a micro- MRI in order to evaluate for elevated intracranial pressure,
vascular etiology in an older adult or elderly patient with an meningitis, and other central nervous system infiltrative
acute CNVI palsy; however, similar to patients with other processes. Finally, an MR venogram can also be considered
types of presumed microvascular ocular motor palsies, in cases where elevated intracranial pressure is suspected.
there is a risk of missing mass lesions, ischemia, or demye-
lination if no further work-up is considered. Despite the
Conclusion
advantages of modern neuroimaging techniques, recent
series have included an “undetermined etiology” in up to Isolated ocular motor neuropathies present a challenge
one-third of adult patients with an isolated palsy.26,27 to physicians. A good rule of thumb is to consider a
 JOURNAL OF BINOCULAR VISION AND OCULAR MOTILITY 7

work-up, including neuroimaging for all acquired cra- 8. Guy JR, Day AL. Intracranial aneurysms with superior
nial neuropathies except for those who are most likely division paresis of the oculomotor nerve.
due to a microvascular etiology in older patients. The Ophthalmology. 1989;96(7):1071–1076. doi:10.1016/
S0161-6420(89)32782-5.
need for urgent neuroimaging in older patients with 9. Ksiazek SM, Repka MX, Maguire A, et al. Divisional
isolated cranial neuropathies thought to be microvas- oculomotor nerve paresis caused by intrinsic brainstem
cular in origin is under debate and requires the physi- disease. Ann Neurol. 1989;26(6):714–718. doi:10.1002/
cian to weigh the risks and benefits of close observation ana.410260605.
with immediate testing. Risk stratification should 10. Barr D, Kupersmith M, Turbin R, Yang S, Lezzi R.
Synkinesis following diabetic third nerve palsy. Arch
include patient-specific data such as age, vascular risk
Ophthalmol. 2000;118:132–134.
factors, duration of symptoms, comorbid medical pro- 11. Liu GT, Carrazana EJ, Charness ME. Unilateral oculo-
blems, and the specific type of CN palsy, with CNIII motor palsy and bilateral ptosis from paramedian mid-
and CNVI palsies generally requiring greater concern brain infarction. Arch Neurol. 1991;48(9):983–986.
than CNIV palsies. The presence of multiple cranial doi:10.1001/archneur.1991.00530210115031.
neuropathies should also raise the level of concern 12. Kissel JT, Burde RM, Klingele TG, Zeiger HE. Pupil-
sparing oculomotor palsies with internal carotid-pos-
and indicate the need for a more urgent work-up. terior communicating artery aneurysms. Ann Neurol.
1983;13(2):149–154. doi:10.1002/ana.410130207.
13. Chou KL, Galetta SL, Liu GT, et al. Acute ocular motor
Conflict of interest mononeuropathies: prospective study of the roles of
neuroimaging and clinical assessment. J Neurol Sci.
Neither of the authors have any financial conflict of interest 2004;219(1–2):35–39. doi:10.1016/j.jns.2003.12.003.
related to this subject matter. 14. Jacobson DM, Trobe JD. The emerging role of mag-
netic resonance angiography in the management of
patients with third cranial nerve palsy. Am J
Funding Ophthalmol. 1999;128(1):94–96. doi:10.1016/S0002-
This work was supported by the Research to Prevent 9394(99)00107-5.
Blindness (unrestricted funds). 15. Trobe JD. Third nerve palsy and the pupil. Footnotes
to the rule. Arch Ophthalmol. 1988;106(5):601–602.
doi:10.1001/archopht.1988.01060130655019.
16. Liu GT, Volpe NJ, Galetta SL. Eye Movement Disorders.
References Neuro-Ophthalmology: Diagnosis and Management.
Philadelphia: Elsevier; 2010.
1. Lee S, Kim SH, Yang HK, et al. Imaging demonstration
17. Norman AA, Farris BK, Siatkowski RM. Neuroma as a
of trochlear nerve agenesis in superior oblique palsy
cause of oculomotor palsy in infancy and early childhood.
emerging during the later life. Clin Neurol Neurosurg.
J AAPOS. 2001;5(1):9–12. doi:10.1067/mpa.2001.112442.
2015;139:269–271. doi:10.1016/j.clineuro.2015.10.027.
18. Raymond LA, Tew J Jr., Fogelson MH. Ophthalmoplegic
2. Volpe NJ, Lee AG. Do patients with neurologically
migraine of early onset. J Pediatr. 1977;90(6):1035–1036.
isolated ocular motor cranial nerve palsies require
doi:10.1016/S0022-3476(77)80598-2.
prompt neuroimaging? J Neuroophthalmol. 2014;34
19. Robertson WC Jr., Schnitzler ER. Ophthalmoplegic
(3):301–305. doi:10.1097/WNO.0000000000000149.
migraine in infancy. Pediatrics. 1978;61:886–888.
3. Patel SV, Mutyala S, Leske DA, Hodge DO, Holmes JM.
20. Harley RD. Paralytic strabismus in children. Etiologic
Incidence, associations, and evaluation of sixth nerve
incidence and management of the third, fourth, and
palsy using a population-based method. Ophthalmology.
sixth nerve palsies. Ophthalmology. 1980;87(1):24–43.
2004;111(2):369–375. doi:10.1016/j.ophtha.2003.05.024.
doi:10.1016/S0161-6420(80)35280-9.
4. Murchison AP, Gilbert ME, Savino PJ. Neuroimaging
21. Holmes JM, Mutyala S, Maus TL, Grill R, Hodge DO,
and acute ocular motor mononeuropathies: a prospec-
Gray DT. Pediatric third, fourth, and sixth nerve palsies:
tive study. Arch Ophthalmol. 2011;129(3):301–305.
a population-based study. Am J Ophthalmol. 1999;127
doi:10.1001/archophthalmol.2011.25.
(4):388–392. doi:10.1016/S0002-9394(98)00424-3.
5. Tamhankar MA, Biousse V, Ying GS, et al. Isolated third,
22. Kodsi SR, Younge BR. Acquired oculomotor, trochlear,
fourth, and sixth cranial nerve palsies from presumed
and abducent cranial nerve palsies in pediatric patients.
microvascular versus other causes: a prospective study.
Am J Ophthalmol. 1992;114(5):568–574. doi:10.1016/
Ophthalmology. 2013;120(11):2264–2269. doi:10.1016/j.
S0002-9394(14)74484-8.
ophtha.2013.04.009.
23. Richards BW, Jones FR Jr., Younge BR. Causes and
6. Bhatti MT, Eisenschenk S, Roper SN, Guy JR. Superior
prognosis in 4,278 cases of paralysis of the oculomotor,
divisional third cranial nerve paresis: clinical and anato-
trochlear, and abducens cranial nerves. Am J
mical observations of 2 unique cases. Arch Neurol.
Ophthalmol. 1992;113(5):489–496. doi:10.1016/S0002-
2006;63(5):771–776. doi:10.1001/archneur.63.5.771.
9394(14)74718-X.
7. Guy J, Savino PJ, Schatz NJ, Cobbs WH, Day AL.
24. Tarczy-Hornoch K, Repka MX. Superior oblique palsy
Superior division paresis of the oculomotor nerve.
or paresis in pediatric patients. J AAPOS. 2004;8
Ophthalmology. 1985;92(6):777–784. doi:10.1016/S0161-
(2):133–140. doi:10.1016/j.jaapos.2003.12.001.
6420(85)33958-1.
8 S. L. PINELES AND F. G. VELEZ

25. Dosunmu EO, Hatt SR, Leske DA, Hodge DO, 28. Afifi AK, Bell WE, Menezes AH. Etiology of lateral
Holmes JM. Incidence and etiology of presumed rectus palsy in infancy and childhood. J Child Neurol.
fourth cranial nerve palsy: a population-based study. 1992;7(3):295–299. doi:10.1177/088307389200700310.
Am J Ophthalmol. 2018;185:110–114. doi:10.1016/j. 29. Moster ML, Savino PJ, Sergott RC, Bosley TM, Schatz
ajo.2017.10.019. NJ. Isolated sixth-nerve palsies in younger adults. Arch
26. Park UC, Kim SJ, Hwang JM, Yu YS. Clinical features Ophthalmol. 1984;102(9):1328–1330. doi:10.1001/
and natural history of acquired third, fourth, and sixth archopht.1984.01040031078029.
cranial nerve palsy. Eye (Lond). 2008;22(5):691–696. 30. Robertson DM, Hines JD, Rucker CW. Acquired sixth-
doi:10.1038/sj.eye.6702720. nerve paresis in children. Arch Ophthalmol. 1970;83
27. Rucker CW. The causes of paralysis of the third, (5):574–579. doi:10.1001/archopht.1970.00990030574008.
fourth and sixth cranial nerves. Am J Ophthalmol. 31. Lee MS, Galetta SL, Volpe NJ, Liu GT. Sixth nerve
1966;61(5 Pt 2):1293–1298. doi:10.1016/0002-9394 palsies in children. Pediatr Neurol. 1999;20(1):49–52.
(66)90258-3. doi:10.1016/S0887-8994(98)00090-3.