176 MAY/JUNE 2005/VOL 42 NO 3

Short Subjects
Drs. Werner and Vaishnav are from the Department of Ophthalmol-
ogy; Dr. Bhatti is from the Departments of Ophthalmology, Neurology, and
Neurological Surgery; Dr. Pincus is from the Departments of Neurological
Surgery and Pediatrics; and Drs. Eskin and Yachnis are from the Depart-
ment of Pathology, University of Florida College of Medicine, Gainesville,
Florida.
Originally submitted December 26, 2003.
Accepted for publication May 10, 2004.
Address reprint requests to M. Tariq Bhatti, MD, Department of
Ophthalmology, University of Florida College of Medicine, Box 100284
JHMHSC, Gainesville, FL 32610-0284.
Supported in part by an unrestricted departmental grant from Research
to Prevent Blindness Inc., New York, New York.
Isolated Anisocoria From an
Endodermal Cyst of the Third
Cranial Nerve Mimicking an
Adies Tonic Pupil
Mark Werner, MD
M. Tariq Bhatti, MD
Hetal Vaishnav, MD
David W. Pincus, MD, PhD
Thomas Eskin, MD
Anthony T. Yachnis, MD
Abstract. We present only the second reported case
in the literature of a neuroenteric cyst involving the
third cranial nerve. Our case is highlighted by the
initial presentation of an isolated anisocoria, ini-
tially believed to represent an Adies tonic pupil as
interpreted by pharmacologic testing. False-positive
results may occur with the dilute pilocarpine test.
J Pediatr Ophthalmol Strabismus 2005;42:176-
179.
INTRODUCTION
Endodermal or neurenteric cysts of the central
nervous system are rare benign lesions frequently in-
volving the spinal cord and less frequently the pos-
terior fossa, supratentorial, and optic nerve.
1-3
They
are believed to occur as the result of a development
anomaly of the notochord during the third week of
embryogenesis.
1,2
Pathologically, the cyst is lled
with high-protein, viscous, cloudy uid lined by co-
lumnar epithelium arising from cells of the gastroin-
testinal or respiratory tracts.
2
We report a case of an endodermal cyst of
the third cranial nerve in a 10-month-old infant.
4

This case highlights the limitations of the dilute
pilocarpine test for detecting cholinergic iris su-
persensitivity when evaluating a patient with an-
isocoria.
CASE REPORT
A 10-month-old infant was referred to the
pediatric ophthalmology service for anisocoria.
The patients mother noticed the infants right
pupil was larger than the left when the infant was
approximately 6 months old. Prior to our evalu-
ation, cranial computed tomography, magnetic
resonance imaging (MRI), magnetic resonance
angiography, abdominal ultrasound, and chest
radiograph were all normal. The ocular motility
examination was normal. There was no ptosis.
Pupillary examination revealed 3 mm of aniso-
coria, with the right pupil being larger than the left.
The anisocoria was accentuated in a lighted room.
The direct and consensual light reaction of the right
pupil was sluggish, and the left pupil was normal.
Both pupils appeared equally round. No prior pho-
tographs were available for comparison. After instil-
lation of 0.125% pilocarpine into both eyes, the
right pupil was found to constrict more than the
left pupil (the degree of anisocoria lessened), indi-
cating an Adies tonic pupil. Cycloplegic refraction
was +0.50 sphere in the right eye and +1.75 sphere
in the left eye. Fundus examination of both eyes re-
vealed no abnormalities.
Six weeks later, the patient returned because the
parents noticed a difference between the two eyes.
On the return examination, the patient exhibited a
left head turn with the right pupil 3 mm larger than
the left with limitation of supraduction, infraduc-
tion, and adduction of the right eye consistent with
third cranial nerve palsy involving the right pupil.
Cranial MRI showed a smooth ring enhancing cys-
JOURNAL OF PEDIATRIC OPHTHALMOLOGY & STRABISMUS 177
tic mass adjacent to the cisternal portion of the third
cranial nerve. The lesion had a homogeneous signal
pattern that was isointense on T1-weighted MRI
and hyperintense on T2-weighted MRI relative to
the cerebral spinal uid (Fig. 1).
A craniotomy was performed with an attempt
at complete surgical resection. Intraoperatively,
the cyst was adherent to the third cranial nerve
and subtotal resection was performed. Pathologi-
cal examination revealed a cystic lesion with well-
differentiated mucin-secreting, respiratory-like
endothelium consistent with an endodermal cyst.
Nerve tissue also was present in the specimen
(Fig. 2).
Postoperatively, the patient had 50 prism diop-
ters (PD) of exotropia, 20 PD of right hypotropia,
and right upper eyelid ptosis. In light conditions,
the right pupil measured 5 mm and the left pu-
pil measured 3 mm. Four months after surgical
resection of the cyst, a right lateral rectus muscle
recession and right medial rectus muscle resection
was performed. Following surgery, the patient dis-
played a residual 15 PD of exotropia and 20 PD of
right hypotropia. Additional strabismus surgery is
scheduled.
DISCUSSION
Endodermal cysts of the central nervous sys-
tem are congenital benign lesions most often in-
volving the spinal cord and posterior fossa.
1,2
Mag-
netic resonance imaging is the preferred method
for radiological evaluation. Because of their high-
protein content, endodermal cysts usually appear
as isotense to slightly hyperintense relative to the
cerebrospinal uid on T1- and T2-weighted MRI
with peripheral enhancement of the cyst after
the administration of contrast.
1,4
It has been sug-
Figure 1. (A) Post-gadolinium axial T1-weighted magnetic resonance image obtained at the level of the midbrain shows subtle pe-
ripheral enhancement of the lesion anterior to the right cerebral peduncle (arrow). (B) Axial T2-weighted magnetic resonance image
obtained at the level of the midbrain shows a round lesion (arrow) with signal characteristics similar to cerebrospinal uid.
A B
Figure 2. (A) Photomicrograph shows the neurenteric cyst lined by a single layer of histologically bland cuboidal to columnar epithe-
lium (original magnication 1,000). (B) Photomicrograph shows the neurenteric cyst epithelium attached to brous stroma (arrows).
A portion of the third nerve is shown in the center and right of the gure (arrows) (original magnication 1,000).
A B
178 MAY/JUNE 2005/VOL 42 NO 3
gested a lobulated appearance of the cyst is more
indicative of an epidermoid cyst, which otherwise
can have similar MRI characteristics to an endo-
dermal cyst.
4
We are aware of only one other pre-
viously published report of an endodermal cyst
involving the third cranial nerve, but unlike our
patient, the cyst occurred in a considerably older
patient.
4
Complete surgical excision of endoder-
mal cysts has been advocated to minimize the risk
of recurrence; however, complete surgical exci-
sion may not be possible because of the lack of a
surgical plane due to the intimate relationship of
the third cranial nerve to the endodermal cyst.
2,4

Therefore, patients and their families should be
counseled on the possibility for incomplete surgi-
cal resection and postoperative worsening of the
ocular motility requiring strabismus surgery.
With any third nerve palsy, unless there is
known destruction of the nerve, waiting at least
6 months is recommended to allow for recovery
of function.
5
However, in our patient, nerve tissue
was observed in the biopsy, indicating early surgi-
cal treatment of strabismus. Treatment of strabis-
mus due to third nerve palsy often requires mul-
tiple surgeries.
5
Adies tonic pupil is characterized by a dilated
pupil that is minimally reactive or unresponsive
to light.
6
When accompanied by reduced or ab-
sent deep tendon reexes, it is known as Adie
syndrome.
6
Diagnosis often is conrmed by phar-
macologic testing.
6,7
Dilute pilocarpine (0.125%)
will cause constriction of the involved pupil with
no effect on the uninvolved pupil because of su-
persensitivity resulting from parasympathetic de-
nervation.
6,7
Adies pupil is uncommon in chil-
dren.
6,8
Tonic pupil presenting in childhood can
result from trauma or infectious causes (ie, vari-
cella).
8
A tonic pupil may cause mild to moderate
anisometropic amblyopia in binocular-viewing
conditions as the result of a relative defect in ac-
commodation.
6
Interpretation of the dilute pilocarpine test
is somewhat controversial.
7
Jacobson has pub-
lished several reports on the subject
7,9
and de-
scribed two endpoints to define cholinergic su-
persensitivity: 1) the pupil of the involved eye
constricts > 0.5 mm relative to the pupil of the
uninvolved eye or 2) the pupil of the involved
eye is larger than the other pupil at baseline and
becomes smaller than the uninvolved pupil.
7,9

Our patient satisfied both of these criteria and
thus initially was believed to have an Adies ton-
ic pupil. However, 6 weeks later, the patient re-
turned with a pupil involving third cranial nerve
palsy. Although a dilute pilocarpine test often
is performed to confirm clinical suspicion of a
postganglionic parasympathetic lesion, the tests
reliability to accurately distinguish an Adies
tonic pupil from a preganglionic third cranial
nerve lesion has been questioned.
9
In addition,
pupil size, amount of anisocoria, and ambient
light conditions of the examination can influ-
ence the interpretation of the test.
7
Therefore,
the present case reinforces the notion that the
results of the dilute pilocarpine test should be
interpreted with caution and careful assessment
of the ocular motility be performed with serial
examinations on all patients with anisocoria.
Several studies have evaluated the causes
of third nerve palsy in children.
5,10
Most com-
monly third nerve palsy is congenital or the
result of trauma, infection, or migraine.
5,10
In
a series of 35 pediatric patients presenting to
the Mayo Clinic with third nerve palsy, tumors
were noted to be the most frequent cause, which
may be a reflection of referral bias.
10,11
In con-
trast to adults, aneurysmal compression of the
third nerve is uncommon.
5
Congenital third
nerve palsy is attributed most often to trauma
to the peripheral portion of the nerve during
delivery, with occasional associated neurologi-
cal deficits.
11
Pupil involvement is variable, and
aberrant regeneration may be present.
5
Ophthal-
moplegic migraine is a syndrome consisting of
episodic pupil-involving third nerve palsy that
begins in childhood.
11
Episodes last less than 3
to 4 days and generally are preceded by severe,
throbbing headache, although headache may oc-
cur at any time.
11
Magnetic resonance imaging
may demonstrate enhancement of the peripheral
third nerve.
12
Meningeal signs, persistent head-
ache, onset after the age of 20 years, lack of fam-
ily history of migraine, and total ophthalmople-
gia should alert clinicians to the possibility of
subarachnoid hemorrhage.
11
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