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REVIEW
open access to scientific and medical research
Open Access Full Text Article
http://dx.doi.org/10.2147/EB.S63633
Horner syndrome: clinical perspectives
Sivashakthi Kanagalingam
1–3
Neil R Miller
1–3
1
Department of Ophthalmology,
2
Department of Neurology,
3
Department of Neurosurgery,
The Johns Hopkins Hospital,
Baltimore, MD, USA
Correspondence: Neil R Miller
Wilmer Eye Institute, The Johns Hopkins
Hospital, Woods 458, 600 North Wolfe
Street, Baltimore, MD 21287, USA
Tel +1 410 502 3213
Fax +1 410 502 3214
Email nrmiller@jhmi.edu
Abstract: Horner syndrome consists of unilateral ptosis, an ipsilateral miotic but normally
reactive pupil, and in some cases, ipsilateral facial anhidrosis, all resulting from damage to the
ipsilateral oculosympathetic pathway. Herein, we review the clinical signs and symptoms that
can aid in the diagnosis and localization of a Horner syndrome as well as the causes of the
condition. We emphasize that pharmacologic testing can confirm its presence and direct further
testing and management.
Keywords: Horner syndrome, oculosympathoparesis, anisocoria, ptosis, anhidrosis
Horner syndrome
The disruption of sympathetic innervation to the eye gives rise to a constellation of
symptoms consisting of miosis, ptosis, and anhidrosis. This syndrome was initially
described in animals by the French physiologist Claude Bernard in 1854
1
and sub-
sequently in a soldier who sustained a gunshot injury to his neck.
2
However, Swiss
ophthalmologist Johann Friedrich Horner is largely credited to be the first to com-
pletely describe this syndrome in 1869 and to correctly attribute it to oculosympathetic
paresis.
3
(Figure 1)
Localization
Central (rst-order neuron) Horner syndrome
First-order neurons are located in the posterolateral hypothalamus, and from there,
sympathetic fibers pass through the lateral brain stem and extend to the ciliospinal
center of Budge and Waller in the intermediolateral gray column of the spinal cord
at C8–T1 (Figure 2). A central Horner syndrome caused by damage to any of these
structures is ipsilateral to the lesion, is almost always unilateral, and often produces
hemihypohidrosis of the entire body.
Lesions of the hypothalamus, such as tumor or hemorrhage, can cause an ipsilat-
eral Horner syndrome with contralateral hemiparesis and contralateral hypesthesia.
4,5
Lesions of the thalamus result in contralateral ataxic hemiparesis, contralateral
hypoesthesia, vertical gaze paresis, and dysphasia.
6
The combination of a unilateral
Horner syndrome and a contralateral trochlear nerve paresis suggests a lesion of the
dorsal mesencephalon. The lesion injures either the trochlear nucleus on the side of the
Horner syndrome or the ipsilateral fascicle.
7–10
Pontine lesions can produce a Horner
syndrome associated with an ipsilateral abducens nerve paresis; however, bilateral
abducens nerve palsies in this setting have also been reported.
11
Number of times this article has been viewed
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Kanagalingam and Miller
Lateral medullary infarction can cause several neurologi-
cal deficits, including a central Horner syndrome. Among 33
consecutive patients with lateral medullary infarction, Horner
syndrome was found in 91%, ipsilateral ataxia in 85%, and con-
tralateral hypalgesia in 85%.
12
These features form the clinical
triad known as the Wallenberg syndrome. Other neurological
features, such as vertigo, dysphagia, nystagmus, and facial
weakness, are less common.
12
Wallenberg syndrome most often
is caused by thrombotic occlusion of the ipsilateral vertebral
artery, although isolated posterior inferior cerebellar artery
disease also can produce this condition.
13
In a series of 130
patients with lateral medullary infarction, the pathogenesis
was large-vessel infarction in 50%, arterial dissection in 15%,
small-vessel infarction in 13%, and cardiac embolism in 5%.
14
Demyelinating disease of the medulla has also been reported
to be the cause of Wallenberg syndrome.
15
Lesions of the lower cervical or upper thoracic spinal
cord can cause a central Horner syndrome. Occasionally,
Horner syndrome may be the only neurological abnormal-
ity at presentation. Spinal cord lesions that may cause a
central Horner syndrome include trauma, inflammatory or
infectious myelitis, vascular malformation, demyelination,
syrinx, syringomyelia, neoplasms, and infarction.
16
Patients
with the Brown-Séquard syndrome from trauma or cervical
Figure 1 Right Horner syndrome in a 65-year-old man. Note right-sided upper lid
ptosis, right miosis, and “upside-down” ptosis (ie, elevation) of right lower lid.
Cilio-
spinal
Center
of
budge
Thoracic
sympathetic
trunk
Lung
Subclavian a
Pupil dilator
Long
ciliary n
2
1
Ophthalmic a
Trigeminal n
Hypothalamus
Midbrain
Pons
Medulla
Orbital vasomotors
lacrimal gland
3
Naso
ciliary n
Sudomotor and
vasoconstrictor fibers to face
Müller’s muscles
of eyelids
Superior
cervical
ganglion
C
8
T
1
T
2
E
x
t
e
r
n
a
l
c
a
r
o
t
i
d
a
I
n
t
e
r
n
a
l
c
a
r
o
t
i
d
a
Figure 2 Drawing showing the anatomy of the oculosympathetic pathway.
Notes: Sympathetic bers in the posterolateral hypothalamus pass through the lateral brain stem and to the ciliospinal center of Budge and Waller in the intermediolateral
gray column of the spinal cord at C8–T1. Preganglionic sympathetic neurons exit from the ciliospinal center of Budge and Waller and pass across the pulmonary apex and
ascend up the carotid sheath to the superior cervical ganglion. The postganglionic sympathetic neurons originate in the superior cervical ganglion and travel up the wall of
the internal carotid artery. Once the bers reach the cavernous sinus, they travel with the abducens nerve before joining the ophthalmic division of the trigeminal nerve
and entering the orbit with its nasociliary branch. From here, they divide into two long ciliary nerves to reach the iris dilator muscle. Copyright © 1978 Wolters Kluwer.
Reproduced with permission from. Glaser JS, editor. Neuro-ophthalmology. 1st ed. Hagerstown MD, USA: Harper & Row; 1978.
133
Abbreviations: a, artery; n, nerve.
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Clinical perspectives on Horner syndrome
disk herniation also have been noted to have a central Horner
syndrome on the same side as the loss of light touch and motor
function and contralateral to the side with the loss of tempera-
ture and pain sensation.
17
A phenomenon termed alternating
Horner syndrome (ie, alternating oculosympathetic deficit)
can be seen in patients with cervical cord lesions and in some
patients with systemic dysautonomias.
18–20
Preganglionic (second-order neuron)
Horner syndrome
The preganglionic sympathetic neurons exit from the ciliospi-
nal center of Budge and Waller and pass across the pulmonary
apex. They then ascend through the stellate ganglion and up
the carotid sheath to synapse at the superior cervical ganglion,
located at the level of the bifurcation of the common carotid
artery and the angle of the jaw.
In a series of 450 patients with Horner syndrome, 270
(65%) were found to have an identifiable cause.
21
Of the
patients with a detectible etiology, 13% had a central lesion,
44% had a preganglionic lesion, and 43% had a postgangli-
onic lesion. In another large series, malignancy was the cause
of about 25% of cases of preganglionic Horner syndrome.
22
The most common tumors were lung and breast cancer.
Horner syndrome usually presents long after the diagnosis
of cancer has been established and only rarely has been part
of the initial presentation.
23
Apical lung lesions that spread locally to the region of
the superior thoracic outlet can cause symptoms of ipsi-
lateral shoulder pain, paresthesias along the medial arm,
forearm, and fourth and fifth digits, weakness/atrophy of the
hand muscles, and a preganglionic Horner syndrome. This
combination of signs is called the Pancoast syndrome. The
most common cause of Pancoast syndrome is non-small cell
lung carcinoma;
24,25
however, other primary apical tumors
such as adenoid cystic carcinoma, hemangiopericytoma,
and mesothelioma, have also been reported to cause this
syndrome.
26–29
Plasmacytoma, non-Hodgkin lymphoma,
lymphomatoid granulomatosis, and metastases are other
infrequent causes.
30–33
A patient with a preganglionic Horner
syndrome and ipsilateral shoulder pain should be investigated
thoroughly for neoplastic involvement of the pulmonary
apex, the pleural lining, and the brachial plexus, as this
feature has been noted to be a reliable sign of underlying
malignancies.
22
Pseudomonal and staphylococcal infections, tuberculosis,
aspergillosis, and cryptococcosis have also been incriminated
in the pathogenesis of Pancoast syndrome.
34–38
Finally, sym-
pathetic chain schwannomas, neuroectodermal tumor, vagal
paraganglioma, and mediastinal tumors or cysts can also
cause a preganglionic Horner syndrome.
39–41
Injury to the brachial plexus or spinal roots, pneumotho-
rax, fracture of the first rib, or neck hematoma are potential
causes of a preganglionic Horner syndrome following trauma.
In addition, the preganglionic sympathetic chains are vulner-
able to iatrogenic injury. The varied anesthetic, radiologic,
and surgical procedures that can produce an iatrogenic Horner
syndrome include coronary artery bypass surgery, lung or
mediastinal surgery, carotid endarterectomy, insertion of a
pacemaker, epidural anesthesia, interpleural placement of
chest tubes, internal jugular catheterization, and stenting of
the internal carotid artery.
42–47
Despite advances in neuroimaging and other diagnostic
tests, as many as 28% of preganglionic Horner syndromes
have no identifiable etiology.
48
Postganglionic (third-order neuron)
Horner syndrome
The postganglionic (third-order) sympathetic neurons origi-
nate in the superior cervical ganglion, travel in the wall of
the internal carotid artery, and continue on to the cavernous
sinus. Within the cavernous sinus, the fibers briefly travel
with the abducens nerve before joining the ophthalmic
division of the trigeminal nerve and entering the orbit with
its nasociliary branch (Figure 3A and B). The sympathetic
fibers in the nasociliary nerve divide into the two long ciliary
nerves that travel with the lateral and medial suprachoroidal
vascular bundles to reach the anterior segment of the eye and
innervate the iris dilator muscle.
49,50
Lesions of the internal carotid artery classically present
with unilateral head and/or neck pain, focal cerebral ischemic
symptoms, and a Horner syndrome. This form of Horner syn-
drome is often referred to as an incomplete Horner syndrome
because it consists of ptosis and miosis but not anhidrosis.
51
This is because the lesion affects the sympathetic fibers in the
internal carotid plexus but spares the external carotid plexus
that innervates the facial sweat glands.
52,53
This painful Horner
syndrome most often is caused by a traumatic or spontaneous
dissection of the cervical internal carotid artery. In a large
series of 146 patients with such lesions, a Horner syndrome
was the most common finding,
54
and in half of these cases
was the initial and sole manifestation.
Internal carotid artery lesions other than dissections that
are associated with a Horner syndrome include aneurysms,
severe atherosclerosis, acute thrombosis, fibromuscular
dysplasia, Ehler–Danlos syndrome, Marfan syndrome, and
arteritis.
55
In addition, mass lesions in the neck, such as
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Kanagalingam and Miller
Internal carotid
sympathetic plexus
VI
ICA
ON
Nasociliary nerve
Long ciliary nasal nerve
V
V
1
B
Figure 3 (A) Cadaver dissection showing oculosympathetic bers (S) attaching (lower arrow) to the abducens nerve (VI) within the cavernous sinus. After running with the
nerve for a short distance, they separate from the nerve (upper arrow) and join with the rst division of the trigeminal nerve (V
1
) to enter the orbit.
Notes: II, optic nerve; III, oculomotor nerve; V, trigeminal ganglion. Copyright © 1978 Wiley-Liss, Inc. Adapted with permission from Parkinson D, Johnston J, Chaudhuri A.
Sympathetic connections to the fth and sixth cranial nerves. Anat Rec. Wiley Publishers. 1978;191:221–226.
49
(B) Artist’s drawing showing that the post-ganglionic
oculosympathetic bers briey travel with the abducens nerve (VI) before joining the ophthalmic division (V
1
) of the trigeminal nerve. Thereafter, the sympathetic bers enter
the orbit with its nasociliary branch. Copyright © 2005, Lippincott Williams. Adapted with permission from Kardon R. Anatomy and physiology of the autonomic nervous
system. In: Miller NR, Biousse V, Kerrison JB, editors. Walsh and Hoyt’s Clinical Neuro-Ophthalmology. 6th ed. Baltimore, MD, USA: Lippincott-Williams & Wilkins; 2005.
134
Abbreviations: ON, optic nerve; ICA, internal carotid artery.
tumors, inflammatory masses, enlarged lymph nodes, and
ectatic jugular veins, can compress the carotid sympathetic
neurons, resulting in a Horner syndrome.
56,57
Damage to the superior cervical ganglion can cause a
postganglionic Horner syndrome as the ganglion lies about
1.5 cm behind the palatine tonsil and can be damaged by
traumatic penetrating intraoral injury or even procedures
such as tonsillectomies, intraoral surgery, and peritonsillar
injections.
58,59
Skull base lesions can cause a postganglionic
Horner syndrome that typically is associated with a variety
of cranial nerve deficits. A middle fossa mass encroaching
on Meckel’s cave and on the internal carotid artery at the
foramen lacerum can produce a Horner syndrome associ-
ated with trigeminal pain or sensory loss. A basal skull
fracture involving the petrous bone can cause a Horner
syndrome with an ipsilateral abduction deficit, facial palsy,
and sensorineural hearing loss.
60
Any lesion in the cavern-
ous sinus may produce a postganglionic Horner syndrome
in conjunction with one or more ocular motor nerves. The
presence of an abducens palsy and a postganglionic Horner
syndrome is highly suggestive of a lesion in the posterior
cavernous sinus.
61–65
Cluster headaches are severe lancinating unilateral head-
aches characterized by ipsilateral tearing, nasal stuffiness,
conjunctival injection, and ptosis. A transient postganglionic
Horner syndrome can be seen in 5%–22% of these patients,
and permanent oculosympathetic paresis has been reported
in some patients who experience repeated attacks.
66,67
Raeder
paratrigeminal neuralgia, a painful postganglionic Horner
syndrome accompanied by ipsilateral trigeminal neuralgia,
is associated with lesions in the middle cranial fossa medial
to the trigeminal ganglion.
68–70
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Clinical perspectives on Horner syndrome
Horner syndrome in children
The causes of Horner syndrome in children are usually
classified as congenital or acquired (Figure 4). In addition
to iris heterochromia, infants with Horner syndrome can
demonstrate contralateral hemifacial flushing and ipsilat-
eral hypohidrosis, called Harlequin syndrome.
71
Congenital
Horner syndrome is usually caused by birth trauma.
71
In these
cases, a history of delivery using forceps, vacuum extraction,
shoulder dystocia, fetal rotation, and/or limb manipulation
can usually be elicited. Concomitant brachial plexus injury is
sometimes identified.
71,72
Other etiologies include congenital
tumors, postviral damage, and internal carotid artery agen-
esis, hypoplasia, and fibromuscular dysplasia.
73–76
In a large study of 73 pediatric patients, 42% were noted to
be congenital in nature, and 42% were acquired after a surgi-
cal procedure involving the thorax, neck, or central nervous
system.
71
Of the other 15% of acquired Horner syndromes,
the etiologies included spinal cord tumors, neuroblastoma,
rhabdomyosarcoma, brachial plexus trauma, intrathoracic
aneurysm, embryonal cell carcinoma, and brain stem vascular
malformations.
71,77
Neuroblastoma is the most common occult malignancy
associated with Horner syndrome, with an incidence of one
in 7,000 children younger than the age of 5 years.
78,79
Early
detection of neuroblastoma is crucial as the prognosis for
survival declines if the diagnosis is made after the age of
1 year.
80,81
Hence, in a child with Horner syndrome in whom
there is no clear history of surgery or birth trauma, a careful
physical examination combined with urinary catecholamine
testing and magnetic resonance imaging of the brain, neck,
and chest is recommended.
82
Using this principle, Jeffery
et al found that 55% of children with an acquired Horner
syndrome had a potentially fatal underlying disease,
71
and
Mahoney et al identified an underlying mass lesion in 21%
of their patients.
82
Nevertheless, it should be noted that
a significant number of pediatric Horner syndromes are
idiopathic. George et al found no etiology in 16 of 23 (70%)
infants with Horner syndrome identified in the 1st year of
life,
83
and Smith et al could not identify an etiology in 35%
of children with a Horner syndrome who were followed for
a mean period of 5 years.
84
Clinical features
Ptosis
The ipsilateral upper eyelid appears slightly drooped due
to paresis of the Müller muscle, a sympathetically inner-
vated smooth muscle that also functions as an upper eyelid
retractor
85,86
and is responsible for about 2 mm of upper
eyelid elevation.
87–89
Nonetheless, this ptosis may be subtle,
variable, and go unnoticed. In addition, one study noted that
in 12% of patients with Horner syndrome, the ptosis was in
fact absent
21
(Figure 1).
The smooth muscle fibers of the lower eyelid retractors
also lose their sympathetic supply in patients with Horner
syndrome and, thus, the lower eyelid appears slightly ele-
vated. This appearance has been termed “upside-down ptosis”
or “reverse ptosis”. The combination of the upper eyelid
ptosis and the lower eyelid elevation narrows the palpebral
fissure, giving rise to an apparent enophthalmos. Several
authors have since proven that this apparent enophthalmos
is not of measurable significance, and hence is not true
enophthalmos.
90–92
Pupillary signs
Oculosympathetic paresis results in weakness of the iris
dilator muscle on the affected side. The unopposed para-
sympathetic action of the iris constrictor muscle produces
a smaller ipsilateral pupil. The resulting anisocoria is most
apparent in darkness and may, in fact, be overlooked if the
patient is evaluated in bright light.
48
Several factors influence the degree of anisocoria in
patients with Horner syndrome. For example, when a patient
is fatigued or drowsy, the size of the pupils and the degree
of anisocoria diminish as the hypothalamic sympathetic out-
flow to both eyes subsides and uninhibited parasympathetic
outflow augments. The actual degree of anisocoria in Horner
syndrome thus varies with the resting size of the pupils, the
patient’s alertness, the patient’s fixation at distance and at
near, the brightness of the examiner’s light, the completeness
of the injury, and the concentration of circulating adrenergic
substances in the blood.
Paresis of the iris dilator muscle also impairs pupillary
movement during dilation, termed dilation lag. Dilation lag
can be seen clinically by illuminating the patient’s eyes tangen-
tially from below with a hand-held flashlight and then abruptly
Figure 4 Infant with right Horner syndrome, demonstrating ipsilateral upper lid
ptosis, “upside-down” ptosis of the lower lid, and anisocoria, with the right pupil
smaller than the left. Both pupils reacted briskly to light stimulation.
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Kanagalingam and Miller
turning the room lights out. The normal pupil will immediately
dilate, but the Horner pupil begins to dilate several seconds
later. The difference in anisocoria is greatest after 4–5 seconds
in the darkness. Thereafter, the Horner pupil slowly dilates
from decreasing parasympathetic tone and eventually catches
up in size to the normal pupil. Thus, if both pupils are observed
simultaneously for 15–20 seconds after turning off the room
light, one sees an initial increase in the degree of anisocoria,
followed by decreasing anisocoria. Continuous recording
pupillography has demonstrated that anisocoria is more marked
at 4–5 seconds in darkness than it is at 10–12 seconds.
93
Taking
photographs in darkness at 5 seconds and again at 15 seconds
can reveal decreasing anisocoria in the later phase of dilation.
94
Videography with infrared illumination can also demonstrate
this phenomenon.
95
Others have reported that a single mea-
surement of anisocoria taken within the first 5 seconds of
darkness is adequate for identifying dilation lag. One study
reported that 0.6 mm or more at 4 seconds was 82% sensitive
for diagnosing a unilateral Horner syndrome.
96
Using binocu-
lar infrared video pupillometry with continuous recording of
pupil diameters, Smith and Smith found that after a light flash,
a delay in the time needed to recover three quarters of the
baseline pupil size had a 70% sensitivity and 95% specificity
in detecting unilateral Horner syndrome.
97
These investiga-
tors also found this method to be useful in detecting cases of
bilateral Horner syndrome.
97
However, using this technology,
Crippa et al noted that dilation lag is only intermittently present
in patients with Horner syndrome,
98
being present in 53% at
the first determination and in 87% at some point during four
determinations. They concluded that although dilation lag is a
notable characteristic of Horner syndrome, it may not always
be evident. Thus, a diagnosis of Horner syndrome should not
eliminated in the absence of a demonstrable dilation lag of
the smaller pupil.
Iris hypochromia
Sympathetic innervation is thought to be required for the
formation of melanin by stromal melanocytes.
72
Interruption
of the sympathetic supply can lead to iris hypochromia on the
affected side. This is a typical feature of congenital Horner
syndrome. It is also occasionally seen in patients with a
long-standing, acquired Horner syndrome, but never in patients
with an acute or recently acquired Horner syndrome.
99
Accommodation
A few authors have noted that patients with Horner syndrome
can experience an increase in accommodative amplitude on
the ipsilateral side.
100,101
Anhidrosis
Characteristic vasomotor and sudomotor changes of the
facial skin can occur on the affected side in some patients
with Horner syndrome. Immediately following sympathetic
denervation, the temperature of the skin rises on the side
of the lesion because of loss of vasomotor control and
consequent dilation of blood vessels. Additionally, there
may be facial flushing, conjunctival hyperemia, epiphora,
and nasal stuffiness in the acute stage.
93,102,103
Some time
after the injury, the skin of the ipsilateral face and neck
may have a lower temperature and may be paler than that
of the normal side. This occurs from supersensitivity of
the denervated blood vessels to circulating adrenergic
substances, with resultant vasoconstriction.
100
However, in
modern temperature-controlled spaces, patients with Horner
syndrome rarely complain of disturbances of sweating or
asymmetric facial flushing.
Paradoxical unilateral sweating with flushing of the face,
neck, shoulder, and arm can be a late development in patients
with a surgically induced Horner syndrome following cervi-
cal sympathectomy. Some axons in the vagus nerve normally
pass into the superior cervical ganglion. These parasympa-
thetic axons can establish, by collateral sprouting, anomalous
vagal connections with postganglionic sympathetic neurons
to the head and neck.
104
Diagnosis
The diagnosis of Horner syndrome should be considered in
any patient with anisocoria associated with what appears to
be normal pupillary constriction to light in both the larger
and smaller pupil. The presence of dilation lag of the smaller
pupil, when present, is also helpful in making the diagnosis.
Patients in whom a Horner syndrome is suspected should be
evaluated for evidence of cranial nerve dysfunction, particu-
larly an ipsilateral abducens nerve paresis that may indicate
a lesion of the cavernous sinus or, in very rare cases, of the
brain stem. Anhidrosis can be diagnosed in some patients
from a history that when they exercise, they perspire on one
side of the forehead but not on the other. In other patients,
the presence of unilateral anhidrosis can be easily assessed
using a metal spoon or similar smooth metal object. Normal
perspiration results in fairly smooth skin. A smooth metal
object that is passed across the forehead, such the undersur-
face of a spoon, thus should slide smoothly; however, in a
patient with a central or postganglionic Horner syndrome
that produces anhidrosis, the spoon will “catch” as it crosses
the forehead on the side of the presumed Horner syndrome.
Pharmacological testing using several agents can establish
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Clinical perspectives on Horner syndrome
kept in a secure, locked storage. Some authors also indicate
that cocaine has a short shelf-life, although this has not been
our experience, with positive responses being elicited despite
using cocaine that has been sitting around for several months!
On the other hand, metabolites of cocaine are excreted in the
urine for up to 2 days after topical administration. This may
pose difficulties for patients who have occupations requir-
ing them to undergo random drug screening. One study of
50 patients found positive urine tests for benzoylecgonine
(a cocaine metabolite) in 100% of patients 24 hours after
topical administration, in 50% at 36 hours, and in 2% after
48 hours.
107
In addition to these issues, a false-positive
response to topical cocaine (ie, lack of dilation in a possible
or presumed Horner pupil) can occur in patients who have a
miotic pupil associated with severe stromal damage to the iris,
neovascularization of the iris, posterior synechiae, or aberrant
regeneration of the oculomotor nerve.
67
Apraclonidine
Apraclonidine is an alpha-2 adrenergic agonist that is some-
times used to lower intraocular pressure in patients with
glaucoma; however, it also has a weak alpha-1 adrenergic
effect. Thus, it minimally constricts a normal pupil but
dilates a Horner pupil due to denervation supersensitivity
of the alpha-1 receptors on its iris dilator muscle, producing
a reversal of anisocoria in patients with unilateral Horner
syndrome
108,109
(Figure 6A and B). Koc et al compared
31 patients with Horner syndrome with 54 healthy controls
using 0.5% apraclonidine.
110
All the Horner pupils had a
mean dilation of 2.04 mm (range 1–4.5 mm), whereas the
pupils of control eyes had a mean constriction of 0.14 mm
(range 0.5–1 mm). Also noted by these investigators was a
mean elevation of 1.75 mm of the upper eyelid on the side of
the Horner syndrome compared with 0.61 mm of elevation
in the eyes of the control group. Eyelid elevation, however,
is not specific to Horner syndrome alone.
110
Although apraclonidine has emerged as an excellent
alternative to cocaine in the diagnosis of Horner syndrome,
several safety concerns have been raised with respect to
its use. Watts et al reported three infants under the age of
6 months who became drowsy after topical administration
of 1% apraclonidine. They further described a 10-week-old
infant who received 0.5% apraclonidine topically in both
eyes and was unresponsive for several hours.
111
Other alpha-
adrenergic receptor agonists, such as brimonidine, have also
been reported to cause bradycardia, somnolence, hypoten-
sion, and lethargy in young children.
112,113
Chen et al reported
no side effects with the use of topical 0.5% apraclonidine in
Figure 5 Cocaine Testing for Horner Syndrome.
Notes: (A) Right Horner syndrome in a 72-year-old man. Note right ptosis and
anisocoria with the smaller pupil on the right side. Both pupils reacted briskly to
light stimulation. (B) After topical administration of 10% cocaine drops in both eyes,
there is marked dilation of the left pupil but the right pupil dilates only very slightly.
This response indicates that the patient has a right Horner syndrome.
the diagnosis of a Horner syndrome in most cases and can
also be used to localize the lesion (see below).
Pharmacological testing
Cocaine
Cocaine is highly effective in confirming the diagnosis of
Horner syndrome.
105
When there is an interruption to the
sympathetic innervation, as occurs in Horner, norepinephrine
is not released from the presynaptic nerve endings. Cocaine
blocks the reuptake of the norepinephrine that is released
from sympathetic nerve endings. This allows norepinephrine
to accumulate at the receptors of the effector cells, thus pro-
ducing dilation of a normal pupil. A Horner pupil, however,
is sympathetically denervated and does not respond to the
circulating norepinephrine (Figure 5A and B). In a normal
eye, a 2%–10% solution of cocaine causes dilation of the
pupil. One study noted a mean pupil dilation of 2.14 mm
(range 0.6–4.0 mm) in normal eyes in response to a 5%
cocaine solution.
48
Forty-five minutes after instillation, an
anisocoria of at least 0.8 mm should be considered indica-
tive of Horner syndrome.
106
However, if the smaller (ie, the
suspected Horner) pupil dilates more than 2 mm, even if the
post-cocaine anisocoria is greater than 0.8 mm, a Horner
syndrome is unlikely.
48
The challenges with using cocaine are many. Because it
is a controlled drug, it can be difficult to obtain and has to be
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Kanagalingam and Miller
Horner syndrome. In our opinion, one should use apraclo-
nidine to try to establish a diagnosis in a presumed acute
Horner syndrome. If there is a positive response (ie, reversal
of anisocoria), this should be taken as indicative of a Horner
syndrome. If there is a negative response, the physician must
decide if the clinical picture warrants pharmacologic testing
with cocaine or further evaluation.
Hydroxyamphetamine
Whereas both cocaine and apraclonidine are useful in the
diagnosis of Horner syndrome, hydroxyamphetamine is use-
ful in distinguishing central and preganglionic lesions from
postganglionic ones.
118–120
Hydroxyamphetamine releases
stored norepinephrine from postganglionic adrenergic nerve
endings, causing mydriasis in normal pupils. With central
and preganglionic lesions, the postganglionic nerve endings
are intact. Thus, after topical administration of a 0.5% solu-
tion of hydroxyamphetamine, a Horner pupil will dilate and
may even become larger than the contralateral normal pupil.
A lesion of the postganglionic sympathetic neurons results
in loss of terminal nerve endings and their respective stores
of norepinephrine. As such, the affected pupil will not dilate
after topical administration of 0.5% hydroxyamphetamine.
121
However, as is the case with apraclonidine, false-negative
results can occur within a week of damage to the postgangli-
onic neurons, as it takes time for the stores of norepinephrine
in the neurons to dissipate.
122
Phenylephrine
Some authors believe that a Horner syndrome can be localized
not only with hydroxyamphetamine but also with a 1% solu-
tion of phenylephrine or a 2% solution of epinephrine.
123,124
These authors suggest that whereas neither a normal pupil
nor a central or preganglionic Horner pupil will dilate when
either of these solutions is instilled, a postganglionic Horner
pupil will dilate after administration of either solution due
to acquired adrenergic supersensitivity of the iris dilator
muscle.
123,124
However, it has also been suggested that regard-
less of the location of the lesion, the Horner pupil will show
denervation supersensitivity.
125
In addition, it must be noted
that denervation supersensitivity may take days to weeks to
develop. Thus, for these reasons, the test may not provide
valid results in either the acute or the chronic setting.
Bilateral Horner syndrome
A bilateral Horner syndrome can be present in patients
with a variety of systemic disorders, including diabetic
autonomic neuropathy, amyloidosis, pure autonomic failure,
Figure 6 Apraclonidine Testing for Horner Syndrome.
Notes: (A) Left Horner syndrome in a 25-year-old man. Note left ptosis and
anisocoria with the smaller pupil on the left. Both pupils reacted briskly to light
stimulation. (B) Forty-ve minutes after topical instillation of 1% apraclonidine in
both eyes, there is reversal of anisocoria, with the right pupil now smaller than the
left. Note also improvement in the left-sided ptosis.
ten children;
114
however, none of the patients in this small
series were under the age of 6 months. Thus, we agree with
others that cocaine is a preferable choice for confirmation of
Horner syndrome in infants and young children.
82
Yet another concern regarding the use of apraclonidine
for the diagnosis of Horner syndrome has been the time
required for supersensitivity of the iris dilator muscle to
develop after interruption of its sympathetic innervation.
Upregulation of the postsynaptic receptors may require a
certain amount of time after oculosympathetic paresis, and
the concern is that a pupil in an acute Horner syndrome
will not dilate in this interim phase.
115
However, Lebas et al
described a patient who developed a Horner syndrome as part
of a dorsal medullary brainstem infarct, and had a positive
apraclonidine test 36 hours after the onset of his symptoms.
116
Another patient who developed Horner syndrome from a
traumatic carotid dissection after a motor vehicle accident
had a positive apraclonidine test a mere 3 hours after the
onset of his symptoms.
117
These cases suggest that apraclo-
nidine may, in fact, be effective in the diagnosis of an acute
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Clinical perspectives on Horner syndrome
Anderson-Fabry disease, familial dysautonomia, and para-
neoplastic syndrome.
97
In a study of 150 patients with gen-
eralized autonomic neuropathy, 58 (38.6%) had evidence of
a Horner syndrome. The syndrome was bilateral in 43 (74%)
of these individuals.
126
Differential diagnosis
Unilateral ptosis and miosis associated with normal pupil-
lary constriction can have other etiologies. Physiological
anisocoria occurs in up to 20% of the normal population,
and some of these patients might have unilateral ptosis ipsi-
lateral to the smaller pupil due to dehiscence of the levator
tendon or other causes.
127
Other causes of anisocoria, such
as a tonic pupil, Argyll Robertson pupils, pharmacologic
pupillary blockade, oculomotor nerve palsy, ocular surgery,
and iris atrophy following inflammation or trauma should
not be confused with a Horner syndrome as such pupils do
not constrict or constrict very slowly to light stimulation. In
addition to dehiscence of the levator tendon, unilateral ptosis
can be caused by other neurologic, myopathic, mechanical,
and neuromuscular conditions.
Evaluation
Once the diagnosis of a Horner syndrome has been con-
firmed, an appropriate evaluation should be performed. As
noted above, in infants and children, this should involve a
complete physical examination, magnetic resonance imaging
of the brain, neck, and chest, and an assay for urinary cat-
echolamines.
82
In adults with an acquired Horner syndrome,
a simple x-ray of the neck in flexion and extension can iden-
tify cervical spondylosis, a common cause of both central
and preganglionic Horner syndromes. In addition, magnetic
resonance imaging of the brain with contrast should reveal
many other causes of a central or postganglionic Horner
syndrome, including brainstem infarct, intracranial tumor,
and demyelinating disease, whereas computed tomographic
scanning of the chest can reveal tumors and other lesions of
the lungs and thorax responsible for preganglionic Horner
syndromes. In addition, computed tomography or magnetic
resonance angiography can effectively evaluate the neck vas-
culature to rule out dissections and other lesions of the ipsilat-
eral internal carotid artery that may cause both preganglionic
and postganglionic Horner syndromes, largely obviating the
need for invasive catheter angiography.
128,129
Davagnanam et al have provided an algorithm to deter-
mine which patients with Horner syndrome should undergo
urgent imaging.
130
They have suggested that a patient with
Horner syndrome with no history of trauma, no pain, and no
localizing signs, does not require urgent imaging but instead
can undergo non-urgent imaging performed within 6 weeks
with clinical reassessment. Nonetheless, it should be noted
that such patients may still have potentially life-threatening
underlying pathology.
131,132
Conclusion
The etiologies of Horner syndrome are numerous, with some
being life-threatening. Thus, the physician who diagnoses a
possible Horner syndrome must carefully assess the patient
for other neurologic manifestations that may help confirm
the diagnosis and be helpful in localizing the site of injury. In
addition to a complete physical examination, pharmacologi-
cal testing is a valuable tool that can aid not only with the
diagnosis but also the localization of a Horner syndrome, so
as to direct further testing and management of the patient.
Disclosure
The authors report no conflicts of interest in this work.
References
1. Kisch B. Horner’s syndrome, an American discovery. Bull Hist Med.
1951;25:284–288.
2. Mitchell SW, Morehouse GR, Keen WW. Gunshot Wounds and Other
Injuries of the Nerves. Philadelphia, PA, USA: Lippincott; 1964.
3. Horner JF. On a form of ptosis. Klin Monatsbl Augenheilkd. 1969;7:
193–198.
4. Stone WM, de Toledo J, Romanul FC. Horner’s syndrome due to hypo-
thalamic infarction: clinical, radiologic and pathologic correlations.
Arch Neurol. 1986,43:199–200.
5. Austin CP, Lessell S. Horner’s syndrome from hypothalamic infarction.
Arch Neurol. 1991;48:332–334.
6. Rosetti AO, Reichhart MD, Bogousslavsky J. Central Horner’s syn-
drome with contralateral ataxic hemiparesis: a diencephalic alternate
syndrome. Neurology. 2003;61:334–338.
7. Nagy AN, Hayman LA, Diaz-Marchan PJ, Lee AG. Horner’s syndrome
due to first-order neuron lesions of the oculosympathetic pathway. AJR
Am J Roentgenol. 1997;169:581–584.
8. Coppeto JR. Superior oblique paresis and contralateral Horner’s
syndrome. Ann Ophthalmol. 1983;15:681–683.
9. Guy JR, Day AL, Mickle JP, Schatz NJ. Contralateral trochlear nerve
paresis and ipsilateral Horner’s syndrome. Am J Ophthalmol. 1989;107:
73–76.
10. Müri RM, Baumgartner RW. Horner’s syndrome and contralateral
trochlear nerve palsy. Neuroophthalmology. 1995;15:161–163.
11. Kellen RI, Burde RM, Hodges FJ 3rd, Roper-Hall G. Central bilateral
sixth nerve palsy associated with a unilateral preganglionic Horner’s
syndrome. J Clin Neuroophthalmol. 1988;8:179–184.
12. Sacco RL, Freddo L, Bello JA, Odel JG, Onesti ST, Mohr JP.
Wallenberg’s lateral medullary syndrome: clinical-magnetic resonance
imaging correlations. Arch Neurol. 1993;50:609–614.
13. Fisher CM, Tapia J. Lateral medullary infarction extending to the lower
pons. J Neurol Neurosurg Psychiatry. 1987;50:620–624.
14. Kim JS. Pure lateral medullary infarction: clinical-radiological correla-
tion of 130 acute, consecutive patients. Brain. 2003;126:1864–1872.
15. Smith DB, Demasters BK. Demyelinative disease presenting as
Wallenberg’s syndrome: report of a patient. Stroke. 1981;12:877–878.
16. Pomerantz H. Isolated Horner syndrome and syrinx of the cervical
spinal cord. Am J Ophthalmol. 2002;133:702–704.
Eye and Brain 2015:7
submit your manuscript | www.dovepress.com
Dovepress
Dovepress
44
Kanagalingam and Miller
17. Kobayashi N, AsamotoS, Doi H, Sugiyama H. Brown-Sequard syndrome
produced by cervical disc herniation: report of two cases and review of
the literature. Spine J. 2003;6:530–533.
18. Kramer W, van der Does de Willebois JJ. Occlusion of the anterior
spinal artery in the cervical cord with sympathetic spasm of the pupil
on finger movement. Folia Psychiatr Neurol. 1959;62:458–464.
19. Furukawa T, Toyokura Y. Alternating Horner syndrome. Arch Neurol.
1974;30:311–313.
20. Tan E, Kansu T, Saygi S, Zileli T. Alternating Horner’s syndrome:
a case report and review of the literature. Neuroophthalmology. 1990;10:
19–22.
21. Maloney WF, Younge BR, Moyer NJ. Evaluation of the causes and
accuracy of pharmacologic localization in Horner’s syndrome. Am J
Ophthalmol. 1980;90:394–402.
22. Thompson H, Maxner C, Corbett J. Horner’s syndrome due to damage
to the preganglionic neuron of the oculosympathetic pathway. In: Huber
A, editor. Symphathetics and the Eye [English Translation]. Stuttgart,
Germany: Ferdinand Enke; 1990.
23. Kovacic S, Lovrencic-Huzjan A, Drpa D, Hat J, Belina S. Horner’s
syndrome as an initial sign of metastatic breast cancer: case report.
Cancer Detect Prev. 2007;31:450–452.
24. Arcasoy SM, Jett JR. Superior pulmonary sulcus tumors and Pancoast’s
syndrome. N Engl J Med. 1997;337:1370–1376.
25. Hilaris BS, Martini N, Wong GY, et al. Treatment of superior sulcus
tumor (Pancoast tumor). Surg Clin North Am. 1987;67:965–977.
26. Ohta Y, Toda A, Ohta N, et al. An atypical lung carcinoid tumor resected
after induction therapy with involvement of the superior sulcus region:
report of a case. Surg Today. 2002;32:632–634.
27. Hatton MQ, Allen MB, Cooke NJ. Pancoast syndrome: an unusual
presentation of adenoid cystic carcinoma. Eur Respir J. 1993;6:
271–272.
28. Chong KM, Hennox SC, Sheppard MN. Primary hemangiopericytoma
presenting as a Pancoast tumor. Ann Thorac Surg. 1993;55:9.
29. Herbut PA, Watson JS. Tumor of the thoracic inlet producing the
Pancoast syndrome: a report of seventeen cases and a review of the
literature. Arch Pathol (Chic). 1946;42:88–103.
30. Chen KT, Padmanabhan A. Pancoast syndrome caused by extramedul-
lary plasmacytoma. J Surg Oncol. 1983;24:117–118.
31. Mills PR, Han LY, Dick R, Clarke SW. Pancoast syndrome caused by
a high grade B cell lymphoma. Thorax. 1994;49:92–93.
32. Dolan G, Smith J, Reilly JT. Extrapulmonary lymphomatoid
granulomatosis presenting as Pancoast’s syndrome. Postgrad Med J.
1991;67:914–915.
33. Rabano A, La Scala M, Hernandez P, Barros JL Thyroid carcinoma
presenting as Pancoast’s syndrome. Thorax. 1991;46:270–271.
34. Vandenplas O, Mercenier C, Trigaux JP, Delaunois L. Pancoast’s
syndrome due to Pseudomonas aeruginosa infection of the lung
apex. Thorax. 1991;46:683H–684H.
35. Gallagher KJ, Jeffrey RR, Kerr SM, Steven MM. Pancoast syndrome:
an unusual complication of pulmonary infection by Staphylococcus
aureus. Ann Thorac Surg. 1992;53:903–904.
36. Vamos G, Papp A. [Pancoast syndrome and lung tuberculosis]. Schweiz
Z Tuberk. 1960;17:423–430. German.
37. Simpson FG, Morgan M, Cooke NJ. Pancoast’s syndrome associated
with invasive aspergillosis. Thorax. 1986;41:156–157.
38. Mitchell DH, Sorrell TC. Pancoast’s syndrome due to pulmonary
infection with Cryptococcus neoformans variety gattii. Clin Infect
Dis. 1992;14:1142–1144.
39. Hood RJ, Jensen ME, Reibel JF, Levine PA. Schwannoma of the cervical
sympathetic chain. Ann Otol Rhinol Laryngol. 2000;109:48–51.
40. Karaman E, Isildak H, Ylimaz M, et al. Management of paragangliomas
in otolaryngology practice: review of a 7-year experience. J Craniofac
Surg. 2009;20:1294–1297.
41. Jindal T, Chaudhary R, Sharma N, Meena M, Dutta R, Kumar A.
Primary mediastinal chondrosarcoma with Horner’s syndrome. Gen
Thorac Cardiovasc Surg. 2011;59:145–147.
42. Gedde SJ, Clark FJ, Johns JA, Johns KJ. Horner’s syndrome as a com-
plication of pacemaker insertion. Am J Ophthalmol. 1991;112:97–99.
43. Barbut D, Gold JP, Heinemann MH, Hinton RB, Trif iletti RR.
Horner’s syndrome after coronary artery bypass surgery. Neurology.
1996;19:181–184.
44. Schachner SM, Reynolds AC. Horner syndrome during lumbar epidural
analgesia for obstetrics. Obstet Gynecol. 1982;59:31S.
45. Jeret JS, Mazurek AA. Acute postpartum Horner’s syndrome due to
epidural anesthesia. Arch Ophthalmol. 1995;113:560.
46. Davis P, Watson D. Horner’s syndrome and vocal cord paralysis as a
complication of percutaneous internal jugular vein catheterisation in
adults. Anaesthesia. 1982;37:587–588.
47. Gasch AT. Horner’s syndrome secondary to chest tube placement.
Ann Ophthalmol. 1996;28:235–239.
48. Wilhelm H, Ochsner H, Kopycziok E, Trauzettel-Klosinski S, Schiefer U,
Zrenner E. Horner’s syndrome: a retrospective analysis of 90 cases and
recommendations for clinical handling. Ger J Ophthalmol. 1992;1:
96–102.
49. Parkinson D, Johnston J, Chaudhuri A. Sympathetic connections of the
fifth and sixth cranial nerves. Anat Rec. 1978;191:221–226.
50. Parkinson D. Further observations on the sympathetic pathways to the
pupil. Anat Rec. 1988;220:108–109.
51. Anson J, Crowell RM. Cervicocranial arterial dissection. Neurosurgery.
1991;29:89–96.
52. Mokri B, Sundt TM Jr, Houser OW, Piepgras DG. Spontaneous dis-
section of the cervical internal carotid artery. Ann Neurol. 1986;19:
126–138.
53. Lee WW, Jensen ER. Bilateral internal carotid dissection due to trivial
trauma. J Emerg Med. 2000;19:35–41.
54. Biousse V, Touboul P-J, D’Anglejan-Chatillon J, Lévy C, Schaison M,
Bousser MG. Ophthalmologic manifestations of internal carotid artery
dissection. Am J Ophthalmol. 1998;126:565–577.
55. Monteiro ML, Coppeto JR. Horner’s syndrome associated with carotid
artery atherosclerosis. Am J Ophthalmol. 1988;105:93–94.
56. Cengiz K, Aykin A, Diren B. Intrathoracic goiter with hyperthyroid-
ism, tracheal compression, superior vena cava syndrome and Horner’s
syndrome. Chest. 1990;87:1005–1006.
57. Inci S, Bertan V, Kansu T, Cila A. Horner’s syndrome due to jugular
venous ectasia. Childs Nerv Syst. 1995;11:533–535.
58. Keane JR. Oculosympathetic paresis: analysis of 100 hospitalized
patients. Arch Neurol. 1979;36:13–16.
59. Liu GT, Deskin RW, Bienfang DC. Horner’s syndrome caused by
intra-oral trauma. J Clin Neuroophthalmol. 1992;12:110–115.
60. Worthington JP, Snape L. Horner’s syndrome secondary to a basilar
skull fracture after maxillofacial trauma. J Oral Maxillofac Surg.
1998;56:996–1000.
61. Striph GG, Burde RM. Abducens nerve palsy and Horner’s syndrome
revisited. J Clin Neuroophthalmol. 1988;8:13–17.
62. Smith EF, Santamarina L, Wolintz AH. Herpes zoster ophthalmicus
as a cause of Horner syndrome. J Clin Neuroophthalmol. 1993;13:
250–253.
63. Myles WM, Maxner CE. Localizing value of concurrent sixth nerve
paresis and postganglionic Horner’s syndrome. Can J Ophthalmol.
1994;29:39–42.
64. Kurihara T. Abducens nerve palsy and ipsilateral incomplete Horner
syndrome: a significant sign of locating the lesion in the posterior
cavernous sinus. Intern Med. 2006;45:993–994.
65. Tsuda H, Ishikawa H, Asayama K, Saito T, Endo S, Mizutani T.
Abducens nerve palsy and Horner syndrome due to metastatic tumor
in the cavernous sinus. Intern Med. 2005;44:644–646.
66. Riley FC, Moyer NJ. Oculosympathetic paresis associated with cluster
headaches. Am J Ophthalmol. 1971;72:763–768.
67. Martin T. Horner’s syndrome, pseudo-Horner’s syndrome, and simple
anisocoria. Curr Neurol Neurosci Rep. 2007;7:397–406.
68. Grimson BS, Thompson HS. Raeder’s syndrome: a clinical review. Surv
Ophthalmol. 1980;24:199–210.
Eye and Brain 2015:7
submit your manuscript | www.dovepress.com
Dovepress
Dovepress
45
Clinical perspectives on Horner syndrome
69. Salvesen R. Raeder’s syndrome. Cephalalgia. 1999;19S:42–45.
70. Goadsby PJ. Raeder’s syndrome: paratrigeminal paralysis of the
oculopupillary sympathetic system. J Neurol Neurosurg Psychiatry.
2002;72:297–299.
71. Jeffery AR, Ellis FJ, Repka MX, Buncic JR. Pediatric Horner syndrome.
J AAPOS. 1998;2:159–167.
72. Weinstein JM, Zweifel TJ, Thompson HS. Congenital Horner’s
syndrome. Arch Ophthalmol. 1980;98:1074–1078.
73. Sayed AK, Miller BA, Lack EE, Sallan SE, Levey RH. Heterochromia
iridis and Horner’s syndrome due to paravertebral neurilemmoma.
J Surg Oncol. 1983;22:15–16.
74. Borzyskowski M, Harris RF, Jones RW. The congenital varicella
syndrome. Eur J Pediatr. 1981;137:335–338.
75. Bayatpour M, Logan J, Perry HP, Finley M. Horner’s syndrome due
to congenital cytomegalovirus infection. South Med J. 1982;75:
220–221.
76. Reader AL 3rd, Massey EW. Fibromuscular dysplasia of the carotid
artery: a cause of congenital Horner’s syndrome? Ann Ophthalmol.
1980;12:326–330.
77. Woodruff G, Buncic JR, Morin JD. Horner’s syndrome in children.
J Pediatr Ophthalmol Strabis. 1988;25:40–44.
78. Bernstein ML, Leclerc JM, Bunin G, et al. A population-based study
of neuroblastoma incidence, survival and mortality in North America.
J Clin Oncol. 1992;10:323–329.
79. Woods WG, Gao R-N, Shuster JJ, et al. Screening of infants and mortal-
ity due to neuroblastoma. N Engl J Med. 2002;346:1041–1046.
80. Nitschke R, Smith EI, Shochat S, et al. Localized neuroblastoma
treated by surgery – a Pediatric Oncology Group study. J Clin Oncol.
1988;6:127–129.
81. Nitschke R, Smith EI, Altshuler G, et al. Postoperative treatment of
non-metastatic visible residual neuroblastoma – a Pediatric Oncology
Group study. J Clin Oncol. 1991;9:1181–1188.
82. Mahoney NR, Liu GT, Menacker SJ, Wilson MC, Hogarty MD, Maris JM.
Pediatric Horner syndrome: etiologies and roles of imaging and urine
studies to detect neuroblastoma and other responsible mass lesions. Am
J Ophthalmol. 2006;142:651–659.
83. George ND, Gonzalez G, Hoyt CS. Does Horner’s syndrome in infancy
require investigation? Br J Ophthalmol. 1998;82:51–54.
84. Smith SJ, Diehl N, Leavitt JA, Mohney BG. Incidence of pediatric
Horner syndrome and risk of neuroblastoma: a population based study.
Arch Ophthalmol. 2010;128:324–329.
85. Anderson RL, Beard C. The levator aponeurosis. Attachments and their
clinical significance. Arch Ophthalmol. 1977;95:1437–1441.
86. Kakizaki H, Malhotra R, Selva D. Upper eyelid anatomy: an update.
Ann Plast Surg. 2009;63:336–343.
87. Carraway JH. Surgical anatomy of the eyelids. Clin Plast Surg. 1987;14:
693–701.
88. Bang YH, Park SH, Kim JH, Cho JH, Lee CJ, Roh TS. The role of Muller’s
muscle reconsidered. Plast Reconstr Surg. 1998;101:1200–1204.
89. Beard C. Muller’s superior tarsal muscle: anatomy, physiology, and
clinical significance. Ann Plast Surg. 1985;14:324–333.
90. Lepore FE. Enophthalmos and Horner’s syndrome. Arch Neurol.
1983;50:460.
91. Van der Wiel HL, Van Gijn J. No enophthalmos in Horner’s syndrome.
J Neurol Neurosurg Psychiatry. 1987;50:498.
92. Nielsen PJ. Upside-down ptosis in patients with Horner’s syndrome.
Acta Ophthalmol. 1983;61:952–957.
93. Pilley S, Thompson H. Pupillary “dilatation lag” in Horner’s syndrome.
Br J Ophthalmol. 1975;59:731–735.
94. Van der Wiel HL, Van Gijn J. Horner’s syndrome: criteria for
oculo-sympathetic denervation. J Neurol Sci. 1982;56:293–298.
95. Verdick R, Thompson HS. Infrared videography of the eyes.
J Ophthalmic Photogr. 1991;13:19–21.
96. Krzizok T, Graf M, Kraus S. [Photo- and videographic determination
of the dilatation deficit in differential diagnosis of Horner syndrome].
Ophthalmologe, 1995;92:125–131. German [with English abstract].
97. Smith SA, Smith SE. Bilateral Horner’s syndrome: detection and
occurrence. J Neurol Neurosurg Psychiatry. 1999;66:48–51.
98. Crippa SV, Borruat FX, Kawasaki A. Pupillary dilation lag is intermit-
tently present in patients with a stable oculosympathetic defect (Horner
syndrome). Am J Ophthalmol. 2007;143:712–715.
99. Diesenhouse MC, Palay DA, Newman NJ, To K, Albert DM. Acquired
heterochromia with Horner syndrome in two adults. Ophthalmology.
1992;99:1815–1817.
100. Cogan DG. Accommodation and the autonomic nervous system. Arch
Ophthalmol. 1937;18:739–766.
101. Cobb S, Scarlett HW. A report of eleven cases of cervical sympathetic
nerve injury causing the oculopupillary syndrome. Arch Neurol
Psychiatry. 1920;3:636–654.
102. Thompson HS. The pupil. In: Adler’s Physiology of the Eye. 9th ed.
St Louis, MO, USA: Mosby-Year Book; 1992.
103. Smith G, Dyches TJ, Burden RM. Topographic analysis of Horner’s
syndrome. Otolaryngol Head Neck Surg. 1986;94:451–457.
104. Romano A, Kurchin A, Rudich R, Adar R. Ocular manifestations
after upper dorsal sympathectomy. Ann Ophthalmol. 1979;11:
1083–1086.
105. Thompson HS. Diagnosing Horner’s syndrome. Trans Am Acad Oph-
thalmol Otolaryngol. 1977;83:840–842.
106. Kardon RH, Denison CE, Brown CK, Thompson HS. Critical evalu-
ation of the cocaine test in the diagnosis of Horner’s syndrome. Arch
Ophthalmol. 1990;108:384–387.
107. Jacobson DM, Berg R, Grinstead GF, Kruse JR. Duration of posi-
tive urine for cocaine metabolite after ophthalmic administration:
implications for testing patients with suspected Horner’s syndrome
using ophthalmic cocaine. Am J Ophthalmol. 2001;131:742–747.
108. Morales J, Brown SM, Abdul-Rahim AS, Crosson CE. Ocular effects
of apraclonidine in Horner syndrome. Arch Ophthalmol. 2000;118:
951–954.
109. Brown SM, Aouchiche R, Freedman KA. The utility of 0.5% apra-
clonidine in the diagnosis of Horner syndrome. Arch Ophthalmol.
2003;121:1201–1203.
110. Koc F, Kavuncu S, Kansu T, Acaroglu G, Firat E. The sensitivity and
specificity of 0.5% apraclonidine in the diagnosis of oculosympathetic
paresis. Br J Ophthalmol. 2005;89:1442–1444.
111. Watts P, Satterfuekd D, Lim MK. Adverse effects of apraclonidine used
in the diagnosis of Horner syndrome in infants. J AAPOS. 2007;11:
282–283.
112. Enyedi LB, Freedman SF. Safety and efficacy of brimonidine in chil-
dren with glaucoma. J JAAPOS. 2001;5:281–284.
113. Carlson J, Zabriskie N, Known T, Barbe ME, Scott WE. Apparent
central nervous system depression in infants after the use of topical
brimonidine. Am J Ophthalmol. 1999;128:255–256.
114. Chen PL, Chen JT, Lu DW, et al. Comparing efficacies of 0.5% apra-
clonidine with 4% cocaine in the diagnosis of Horner’s syndrome in
pediatric patients. J Ocul Pharmacol Ther. 2006;22:182–187.
115. Kardon R. Are we ready to replace cocaine with apraclonidine in the
pharmacologic diagnosis of Horner syndrome? J Neuroophthalmol.
2005;25:69–70.
116. Lebas M, Seror J, Debroucker T. Positive apraclonidine test 36 hours
after acute onset of Horner syndrome in dorsolateral pontomedullary
stroke. J Neuroophthalmol. 2010;30:12–17.
117. Cooper-Knock J, Pepper I, Hodgson T. Early diagnosis of Horner
syndrome using topical apraclonidine. J Neuroophthalmol. 2011;31:
214–216.
118. Thompson HS, Mensher JH. Adrenergic mydriasis in Horner’s syn-
drome: hydroxyamphetamine test for diagnosis of postganglionic
defects. Am J Ophthalmol. 1971;72:472–480.
119. Cremer SA, Thompson HS, Digre KB, Kardon RH. Hydroxyamphetamine
mydriasis in Horner’s syndrome. Am J Ophthalmol. 1990;110:
71–76.
120. Thompson HS, Mensher JH. Hydroxyamphetamine test in Horner’s
syndrome. Am J Ophthalmol. 1975;79:523–526.
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Kanagalingam and Miller
121. Cremer SA, Thompson HS, Digre KB, Kardon RH. Hydroxyamphet-
amine mydriasis in normal subjects. Am J Ophthalmol. 1990;110:
66–70.
122. Donahue SP, Lavin PJ, Digre K. False-negative hydroxyamphetamine
(Paredrine) test in acute Horner’s syndrome. Am J Ophthalmol.
1996;122:900–901.
123. Ramsay DA. Dilute solutions of phenylephrine and pilocarpine in the
diagnosis of disordered autonomic innervation of the iris. Observations
in normal subjects, and in the syndromes of Horner and Holmes-Adie.
J Neurol Sci. 1986;73:125–134.
124. Danesh-Meyer HV, Savino P, Sergott R. The correlation of phenyleph-
rine 1% with hydroxyamphetamine 1% in Horner syndrome. Br J
Ophthalmol. 2004;88:592–593.
125. Smit DP. Pharmacologic testing in Horner’s syndrome – a new
paradigm. S Afr Med J. 2010;100:738–740.
126. Bremner F, Smith S. Pupil findings in a consecutive series of
150 patients with generalized autonomic neuropathy. J Neurol
Neurosurg Psychiatry. 2006;77:1163–1168.
127. Ettinger ER, Wyatt HJ, London R. Anisocoria: variation and
clinical observation with different conditions of illumination and
accommodation. Invest Ophthalmol Vis Sci. 1991;32:501–509.
128. Levy C, Laissy JP, Raveau V, et al. Carotid and vertebral artery dissec-
tions: three dimensional time-of flight MR angiography and MR imag-
ing versus conventional angiography. Radiology. 1994;190:97–103.
129. Leclerc X, Godefroy O, Salhi A, Lucas C, Leys D, Pruvo JP. Helical
CT for the diagnosis of extra-cranial internal carotid artery dissection.
Stroke. 1996;27:461–466.
130. Davagnanam I, Fraser CI, Miszkiel K, Daniel CS, Plant GT. Adult
Horner’s syndrome: a combined clinical, pharmacological, and imag-
ing algorithm. Eye (London). 2013;27:271–298.
131. Lee SYS, Mollan S, Senthil L, et al. Aetiology and Investigation of
Adult Acquired Horner Syndrome. Presented at the United Kingdom
Neuro-ophthalmology Special Interest Group, Glasgow, Scotland,
March 13, 2013.
132. Al-Moosa A, Eggenberger E. Neuroimaging yield in isolated Horner
syndrome. Curr Opin Ophthalmol. 2011;22:268–271.
133. Glaser JS. editor, Neuro-ophthalmology. 1st ed. Hagerstown MD,
USA: Harper & Row; 1978.
134. Kardon R. Anatomy and physiology of the autonomic nervous system.
In: Miller NR, Biousse V, Kerrison JB, editors. Walsh and Hoyt’s Clini-
cal Neuro-Ophthalmology. 6th ed. Baltimore, MD, USA: Lippincott-
Williams & Wilkins; 2005:649–714.
