Andrew S.

Gurwood, OD, FAAO

Horners syndrome
In the first of a three-part series on pupils,
Dr Andrew Gurwood looks at Horners syndrome.
SIGNS AND SYMPTOMS
Horners syndrome is characterised by an
interruption of the oculosympathetic nerve
supply somewhere between its origin, in the
hypothalamus and the eye1-9 (Figure 1).
The classic clinical findings associated with
Horners syndrome are ptosis, pupillary
miosis, facial anhidrosis, apparent
enophthalmos, increased amplitude of
accommodation, heterochromia of the
irides (if before age two or congenital),
paradoxical contralateral eyelid retraction,
transient decrease in intraocular pressure
and changes in tear viscosity1-9.
Horners syndrome has no predilection
for age, race, gender or geographic
location. Horners syndromes of congenital
origin present around the age of two years
with heterochromia and absence of a
horizontal eyelid fold or crease in the ptotic
eye1-5,9. Iris pigmentation (which is under
sympathetic control during development)
is completed by the age of two, making
heterochromia an uncommon finding in
Horners syndromes acquired later in life1-3.
Old photographs can aid the clinician in
distinguishing congenital Horners by
documenting heterochromia present at
birth1-5.
PATHOPHYSIOLOGY
Sympathetic innervation to the eye
consists of a three neuron arc1-9. The first
neuron originates in the dorsolateral
hypothalamus. It descends through the
reticular formation of the brainstem and
travels to the ciliospinal centre of Budge
between the levels of the eighth cervical
and fourth thoracic vertebrae (C8-T4) of
the spinal cord. There, it synapses with
second order neurons whose
preganglionic cell bodies give rise to axons,
which exit the white rami communicantes
of the spinal cord via the anterior horn.
These axons pass over the apex of the lung
and enter the sympathetic chain in the
neck, synapsing in the superior cervical
ganglion1-9. Here, cell bodies of third order
neurons give rise to post-ganglionic axons
that course to the eye with the internal
36

carotid artery via the cavernous sinus1-9.

Fibres from these axons form the long and
short posterior ciliary nerves of the eye.
These sympathetic nerve fibers course
anteriorly through the uveal tract and join
the fibres of long posterior ciliary nerves,
which course with branches of the fifth
cranial nerve, to innervate the dilator of
the iris. Post-ganglionic sympathetic fibres
also innervate the muscle of Mller,
responsible for the initiation of eyelid
retraction during eyelid opening. Postganglionic sympathetic fibres responsible
for facial sweating, follow the external
carotid artery to the sweat glands of the
face1-9. Interruption at any location along
this pathway (pre-ganglionic or postganglionic) will induce an ipsilateral
Horners syndrome.
DIFFERENTIAL DIAGNOSIS
The diagnosis and the localisation of a
Horners syndrome can be accomplished
with pharmacological testing5-9. Topically
applied, 10% cocaine works as an indirect
acting sympathomimetic agent producing
pupillary dilation in the normally
innervated pupil by inhibiting the reuptake of norepinephrine at the nerve
ending4-9. A Horners pupil will dilate
poorly compared to the normal eye because
of the absence of norepinephrine at the
nerve ending4-9. The test should be
evaluated 30 minutes after the instillation
of the drops to ensure accuracy. The
cocaine test is used to confirm or deny the
presence of a Horners syndrome. A
positive cocaine test does not localise the
lesion1-9. The nature of the diagnostic agent
means that, in the UK, confirmation of an
ophthalmologist is required, necessitating
referral.
To localise the lesion as either
preganglionic (neurons 1 or 2 before the
synapse in the superior cervical ganglion)
or post-ganglionic (after exiting the
superior cervical ganglion), Paradrine 1%
(hydroxyamphetamine) or Pholedrine
5%
(n-methyl
derivative
of
hydroxyamphetamine) can be instilled 48

JUNE 4 1999 OPTOMETRY TODAY

hours later. Pholedrine and Paradrine act

similarly by producing the forced release of
endogenous norepinephrine from the
presynaptic vesicles. If the third neuron is
damaged, the pupil will not dilate,
indicating a post-ganglionic lesion1-9. There
is currently no method of topical testing to
differentiate a first order pre-ganglionic
lesion from a second order pre-ganglionic
lesion7.
The common aetiologies of acquired
Horners syndrome include, but are not
limited to, trauma, aortic dissection,
carotid dissection, tuberculosis and
Pancoast tumour1-9.
Aortic dissection is a tear in the
intimal region of the ascending aorta near
the aortic valve1-9. It often occurs along the
right lateral wall of the ascending aorta
where the hydraulic stress is the greatest1-9.
Compression of adjacent tissues (e.g.
superior cervical ganglia, superior vena
cava, bronchus, esophagus) by the
expanding dissection, can result in
Horners syndrome, superior vena cava
syndrome, vocal cord paralysis, hoarseness,
dysapnea, and dysphagia21,22. Patients with
long-standing systemic hypertension,
Marfans syndrome and Ehlers Danlos
syndrome are at increased risk1-9.
Tuberculosis (TB) is a chronic
i n f e c t i o u s d i s e a s e c a u s e d b y the
organism Mycobacterium tuberculosis1-9.
TB is an airborne disease that is
transmitted from person to person by the
inhalation of infected air droplets. TB may
infect any organ in the body, however, the
lungs are the most prevalent site of
involvement8,9. Tubercles (from which the
name of the disease is derived) are
granulomatous inflammations, which
invade the lung and induce tissue necroses
referred to as caseations9. If the tubercle
occupies a position at the lung apex, it may
compress pre-ganglionic sympathetic
axons producing a Horners syndrome.
Diagnosis can be made with a purified
protein derivative (PPD) accompanied
with an anergy panel9. A chest X-ray and
erythrocyte sedimentation are also helpful
in confirming diagnosis.
Pancoast tumour, or superior
pulmonary sulcus carcinoma, was first
described in 1924 by H.K. Pancoast10.

Horners syndrome
Clinical characteristics of Pancoast tumour
include shoulder pain, loss of limb function,
atrophy of the muscles of the hand,
Horners syndrome and dullness of feeling
in the region of the upper chest10.
A true Pancoast tumour usually extends
through the visceral pleura into the parietal
pleura and chest wall The tumour is
considered to be epithelial in its
histopathology, but its exact origin remains
uncertain Despite its small size and general
lack of metastasis, Pancoast tumour has a
rapid and almost universal mortality rate.
Approximately 80-90% of all lung cancers
are linked or associated with smoking10.
Other risk factors include exposure to
asbestos, radon gas, uranium, arsenic
fumes, isopropyl oil, nickel, metallic iron,
iron oxide and beryllium.
MANAGEMENT
In general, the treatment for Horners
syndromes depends upon the cause. In
many cases, there is no treatment that
improves or reverses the condition.
Treatment in acquired cases is directed
toward erradicating the disease that is
producing the syndrome. Recognising the
signs and symptoms is tantamount to early
diagnosis and expedient referrals to
specialists.
The serious implications associated
with a suspicion of Horners syndrome
merits ophthalological referral whereupon
confirmatory pharmocological testing may
be undertaken along with other dignostic
tests, eg chest X-ray. This is a condition
which optometrists need to be alert to.

Table 1: Aetiology summary for Horners syndrome

CONGENITAL HORNERS SYNDROME

Secondary to brachial plexus injury during delivery

PRE-GANGLIONIC
A. Central

Cerebrovascular accident (stroke), lateral medullary

infarction, trauma to the neck region, space
occupying lesion (tumour), demylinating diease

B. Peripheral

Mediastinal mass, trauma to the neck region,

iatogenic injury following thyroidectomy,
Pancoasts tumour (tumour of the uppermost
portion of the lung)

POST-GANGLIONIC

Trauma or lesion of the neck, head trauma, lesion

of the cavernous sinus, carotid cavernous fistula,
carotid artery aneurysm, carotid artery dissection,
nasopharyngeal carcinoma, vascular disease,
infection (complicated otits media) and migraine
Pre-ganglionic Horners lesions are more ominous
Laboratory investigations may include
pharmacologic ocular testing, cervical spine X-ray,
computed axial tomography (CT scan), magnetic
resonance imaging (MRI), complete blood count
and lymph node biopsy

Table 2: Pharmocologic testing summary

TOPICAL COCAINE 2-10%

is used to confirm or deny the presence of Horners

syndrome. Cocaine is a sympathomimetic that
blocks the reuptake of norepinehpherine.
a. Place 2 drops in both eyes
b. Check both eyes after 30 minutes
c. Normal pupils dilate
d. Horners syndrome pupils do not dilate as the
3 neuron pathway has been interrupted

TOPICAL HYDROXYAMPHETAMINE
1% (PAREDRINE)

can be used to confirm 3rd neuron damage.

Hydroxyamphetamine stimulates the release of
norepinepherine from neurons.
a. Place one drop into both eyes
b. Central or preganglionic lesions dilate as the
3rd neuron is intact
c. Post-ganglionic lesions do not dilate

ABOUT THE AUTHOR

Dr Andrew Gurwood is Associate Professor
of Clinical Sciences at the Eye Institute of
the Pennsylvania College of Optometry,
Philadelphia.
REFERENCES
1. Wilkins, R.H., Brody, I.A., Durham, N.C. (1968)
Horners syndrome. Arch. Neurol. 19: 540-542.
2. Horner, F. (1869) Uber eine form von ptosis.
Klin. Monatsbl. Augenh. 7: 193.
3. Tantum, L.A. Pupil anomalies.
In Onofrey, B.E. ed (1991)
4. Clinical Optometric Pharmacology and
Therapeutics.
J.B. Lippincott Co, Philadelphia, 13: 1-13.
5. Burde, R.M., Savino, R.J., Trobe, J.D.
Anisocoria and abnormal pupillary light
reaction. In Burde, R.M., Savino, P.J., Trobe,
J.D. eds (1992)
6. Clinical Decisions in Neuro-ophthalmology
2nd ed. Mosby Year Book, St Louis, 321-346.

7. Myles, W.M., Maxner, C.E. (1994) Localizing

value of concurrent sixth nerve paresis and
postganglionic Hornerss syndrome.
Can. J. Ophthalmol. 29 91 0: 39-42.
8. Maloney, W.F., Younge, B.R., Moyer, N.J. (1980)
Evaluation of the causes and accuracy of
pharmacologic localization in Horners
syndrome. Am. J. Ophthalmol. 90: 394-402.
9. Bates, A.T., Chamberlain, S., Champion, M. et al
(1995) Pholedrine- a substitute for
hydroxyamphetamine as a diagnosis eye drop
test in Horners syndrome. J. Neurology,
Neurosugery and Psychiatry 58: 215-217.
10. Thompson, H.S., Pilley, S.F.J. (1976) Unequal
pupils - a flow chart for sorting out the
anisocorias. Survey Ophthalmol. 21(1): 45-48.

JUNE 4 1999 OPTOMETRY TODAY

11. Cullom, R.D., Chang, B. Neuroophthalmology: Horners syndrome. In

Cullom, R.D., Chang, B. eds (1993)
12. The Wills Eye Manual 2nd ed. J.B.
Lippincott Co, Philadelphia, 241-246.
13. Sartori, F., Rea, F., Calabro, F. et al (1992)
Carcinoma of the superior pulmonary
sulcus. J. ThoracCardiovasc. Surg. 104:
679-683.

The next article will look

at tonic pupils.

37