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Horner Syndrome - StatPearls - NCBI Bookshelf
Horner Syndrome - StatPearls - NCBI Bookshelf
Objectives:
Introduction
Horner syndrome is a rare condition classically presenting with partial ptosis (drooping or falling of upper eyelid), miosis
(constricted pupil), and facial anhidrosis (loss of sweating) due to a disruption in the sympathetic nerve supply. It is primarily
acquired following damage to the sympathetic nerve supply, but rare cases of congenital forms have been seen. Therefore,
treatment is centered around identifying and appropriate management of the underlying secondary cause.
The syndrome has several names, such as Bernard-Horner syndrome (French-speaking countries), Horner syndrome (English
speaking countries), oculosympathetic palsy, and Von Passow syndrome (Horner syndrome in association with iris
heterochromia).
The syndrome was first described by Francois Pourfour du Petit in 1727 when considering results from an animal experiment
involving resection of intercostal nerves and subsequent changes seen in the ipsilateral eye and face.[1] It was outlined more
thoroughly by the French physiologist Claude Bernard in 1852, followed by several physicians who offered different
interpretations.
The condition was formally described and later named after Swiss ophthalmologist Johann Friedrich Horner in 1869.[2][3][4]
[5]
Anatomy
Understanding the sympathetic innervation of the eye is vital to understanding the features of this syndrome. The nerve supply
is constituted by three different neurons, starting from the posterolateral hypothalamus and ending as the long ciliary nerves to
supply the iris dilator and superior tarsal muscles (Muller muscle).[6]
The first-order neurons originate from the hypothalamus and descend through the midbrain and pons uncrossed, terminating at
the C8-T2 level of the spinal cord in the intermediolateral cell columns (ciliospinal center of Budge). Second-order
preganglionic neurons exit at the T1 level of the spinal cord to enter the cervical sympathetic chain, where the fibers ascend to
synapse in the superior cervical ganglion at the C3-C4 level.[7]
:
Third-order, postganglionic fibers branch off into the sudomotor and vasomotor fibers, which follow the external carotid
artery and innervate the sweat glands and blood vessels of the face. The remaining fibers ascend along the internal carotid
artery in the carotid plexus to eventually enter the cavernous sinus, where they join the abducens nerve (CN VI). The fibers
then exit the cavernous sinus to enter the orbit via the superior orbital fissure and the ophthalmic branch (V1) of the trigeminal
nerve (CN V) as the long ciliary nerves.
Etiology
Horner syndrome is primarily an acquired condition secondary to systemic/local diseases or iatrogenic causes but maybe
congenital and purely hereditary in some rare cases.[8][9] Sympathetic fibers have an extensive course and can be interrupted
during extracranial, intracranial, or intra-orbital traversal.[10][11][12] The sympathetic fibers may be interrupted centrally,
between the hypothalamus and the exit point of fibers from the spinal cord (C8 to T2), or the discontinuation could be
peripheral, in the cervical sympathetic chain, at the level of superior cervical ganglion, or along the course of the carotid
artery.[10] Preganglionic Horner syndrome can be an ominous sign due to its association with pulmonary malignancies.
Overall, the causes of Horner syndrome can be divided according to the anatomical location of disruption.
First-order neurons are mostly affected by intracranial conditions and include the following:[13][14][15]
Second-order neurons traverse the thoracic region and are affected by the following:
Third-order neurons are in close proximity to the internal carotid artery and cavernous sinus and are affected by the following:
Epidemiology
:
Horner syndrome is uncommon, occurring with a frequency of approximately 1 per 6,000. It may occur at any age or with any
ethnic group.[15][19]
Pathophysiology
As previously described, Horner syndrome is a consequence of sympathetic disruption. The symptomology depends on the
location of the lesion, and severity depends on the degree of denervation.[9]
Superior tarsal muscle helps raise the upper eyelid and has a sympathetic nerve supply. Denervation of this muscle causes
ptosis, which is milder than oculomotor (CN III) palsy which supplies the levator palpebrae superioris. The superior tarsal
muscle is responsible for keeping the upper eyelid in a raised position after levator palpebrae superioris raises it. This explains
the partial ptosis seen in Horner syndrome. The lower eyelid may be slightly elevated owing to denervation of the lower lid
muscle, which is analogous to the superior tarsal muscle.[20]
The sympathetic nervous supply is responsible for pupil dilationupil (mydriasis). When disrupted, parasympathetic supply is
uninhibited, and constriction of the pupil (miosis) ensues. The reaction of the pupils to light and accommodation is normal as
those systems do not depend on sympathetic nerve supply.[21]
Ipsilateral anhidrosis, another classic presentation, depends on the level of interruption of the sympathetic supply. Anhidrosis
with first-order neuron lesions affects the ipsilateral side of the body as the sympathetic supply from its central origin.[22] The
ipsilateral face is involved in lesions involving the second-order neurons. Postganglionic third-order neuron lesions after the
vasomotor and sudomotor fibers have branched off show very limited involvement of the face (area adjacent to the ipsilateral
brow).
Iris heterochromia (relevant deficiency of pigment in the iris on the affected side) is seen in children younger than 2 years and
is the congenital form of Horner syndrome.[9]
Balance, hearing, sensory, and swallowing problems can point towards a more central process involving the first-
order neurons.
Prior history of trauma or surgical intervention involving the head, face, neck, shoulder, or back points towards the
involvement of second-order neurons.[17]
A detailed past medical and medication history to rule out the use of a miotic or mydriatic agent.
A headache, double vision, facial numbness, or pain indicate third-order neuron involvement.
The presence of anhidrosis and its location can help in the localization.
A detailed history of a headache if present.
Longstanding symptoms point towards a more benign underlying cause versus recently progressive symptoms such
as weight loss, hemoptysis, low-grade fever, and lymphadenopathy.
Facial flushing suggests a preganglionic lesion.[23]
Facial or orbital pain in combination with miosis and ptosis should point towards Raeder paratrigeminal syndrome.
[24]
History of skin lesions or previously diagnosed herpes zoster infection.
Severity and location of the pain.
A detailed examination of the eyes is warranted and should include the following:
A detailed exam can reveal a round and constricted pupil. The affected pupil exhibits dilation lag (dilates more slowly), and
the unequal pupils are appreciated more in darkness compared to light. In addition, the ciliospinal reflex may be absent.
Furthermore, partial ptosis, iris heterochromia, apparent enophthalmos, contralateral eyelid retraction, injected conjunctivae,
and no change or a transient decrease in intraocular pressure may be seen.[25][18][17]
It is important to perform a detailed systemic examination, paying specific attention to neurological, pulmonary, and
cardiovascular systems and considering various differentials discussed later.
Evaluation
Labs
The initial workup should include a complete blood count (CBC), erythrocyte sedimentation rate (ESR), and serum
chemistry panel.
Urine or blood cultures may be ordered if an infectious agent is suspected.
Testing for suspected neurosyphilis, HIV, thyroid function, vitamin B-12, and folate levels may be ordered if
indicated following detailed history and examination.
Urine testing for elevated metabolic catecholamine by-products is important in the pediatric population with
suspected neuroblastoma.
Purified protein derivative (PPD) is warranted in suspected tuberculosis.
Imaging
A chest X-ray followed by computed tomography (CT) scan must be ordered in patients when pulmonary
malignancy is suspected.
Head CT and magnetic resonance imaging (MRI) are advised in cases of possible stroke.
MRI is warranted and preferred over ultrasonography when carotid artery dissection is a possibility (painful Horner
syndrome).[26]
Pharmacological Testing
Topical Cocaine Test: Cocaine acts as an indirect sympathomimetic inhibiting the reuptake of norepinephrine from the
synaptic cleft. Cocaine solution (ranging from 2% to 10%) is instilled into both eyes. Both eyes are evaluated after at least 30
or more minutes for an optimal response. Denervation in the affected eye causes it to dilate poorly compared to the normal
one. Anisocoria of 0.8 mm or more is considered diagnostic. However, the test does not help in identifying the level of the
lesion.
The test has other disadvantages such as comparatively high prices of the compound, time-consuming, test yielding
ambiguous results, and the metabolites of cocaine can be detected in urine.[28]
Topical Hydroxyamphetamine Test: This test is particularly helpful in the localization of the lesion. Hydroxyamphetamine
stimulates the release of stored norepinephrine from the postganglionic terminals into the synapse. Postganglionic third-order
lesions can be differentiated from presynaptic second-order or first-order ones.
Two drops of 1% hydroxyamphetamine solution are instilled into both eyes. As a result, the affected eye (third-order lesion)
:
will not dilate as well as the normal eye. While in the case of intact postganglionic fibers (first and second-order lesions), the
affected pupil dilates to an equal or greater extent.
Disadvantages involving this test include it not being able to be performed on the same day as the cocaine test and false-
negative results.[28]
Topical Apraclonidine Test: This test is considered the test of choice due to its good sensitivity and overall practicality.
Apraclonidine acts as a weak alpha1-agonist and strong alpha2-agonist. It is categorized as an ocular hypotensive agent. The
upregulation of alpha1-receptors in Horner syndrome translates into an exaggerated response of the iris dilators (denervation
supersensitivity) to an agonist agent like apraclonidine.[29]
A 0.5-1% solution is instilled in both eyes. The affected eye will show mydriasis, while the normal eye is predominantly
insensitive. Consequent instillation of the solution results in an evident reversal of anisocoria (the affected pupil dilates and
the normal pupil constricts). This is because of the stronger alpha 2 agonist activity compared to the weaker alpha 1 agonist
activity of apraclonidine.
Some disadvantages of this form of testing include false-negative results in acute cases, systemic side effects in the pediatric
population, inability to localize the lesion, and relatively long half-life of the drug.
Other agents have been proposed but fall short of clinical relevance due to several reasons, such as:
Treatment / Management
Treatment options are based on the diagnosis and management of the underlying cause. Timely diagnosis is of critical
importance, followed by referral to an appropriate specialist. Healthcare professionals are advised to incorporate the
importance of eye examinations into their acumen.
Whether surgical intervention is indicated and what type is appropriate largely depends on the cause of the disease. Surgical
treatment options include the following:
Di!erential Diagnosis
As previously described, pain accompanied by Horner syndrome points towards a more insidious underlying cause and should
be evaluated thoroughly. Systemic symptoms such as weight loss and progressive fatigue can indicate an underlying
malignancy. Furthermore, Horner syndrome can be an early manifestation of neuroblastoma in the pediatric population.
Carotid artery dissection can present with a unilateral headache and facial or neck pain. If suspected, urgent appropriate
workup and treatment are warranted.
Raeder paratrigeminal syndrome also can present with headaches but is accompanied by trigeminal nerve (CN V) impairment.
Anisocoria and/or ptosis can be due to myriad diseases and conditions such as Holmes-Adie syndrome, neurosyphilis (Argyll
Robertson pupil), third nerve palsy, or optic neuritis.
Prognosis
:
Prognosis
The long-term prognosis of idiopathic Horner syndrome appears to be benign. Clinically, patients do not generally become
worse, and in fact, half of the patients no longer experience anisocoria. Almost a third of patients with ptosis notice
spontaneous improvement or complete resolution in a mean duration of 7.9 years after Horner syndrome is diagnosed. In
unilateral cases, the oculo-sympathetic defect does not progress to become bilateral. It is possible that new medical disorders
later develop between 3 and 20 years after the diagnosis of Horner syndrome; none are usually related to Horner syndrome.
[31]
Complications
Horner syndrome is almost always secondary to an underlying cause, such as tumor, trauma, infection, etc, and is rarely
idiopathic. The complications that occur as a result of Horner syndrome are essentially related to the cause of Horner
syndrome. For instance, if Horner syndrome is secondary to multiple sclerosis, it could lead to muscle stiffness or spasms,
impaired bladder, bowel, or sexual function; and seizures. Similarly, Horner syndrome-related eye problems can lead to
problems with vision that could be temporary or permanent. Visual involvement can lead to partial or complete blindness.
Consultations
For the appropriate management of Horner syndrome and the underlying cause, the following consultations may be needed:
Pulmonology
Neurology
Neurosurgery
Interventional radiology
Oncology
Neuro-ophthalmology
Review Questions
Access free multiple choice questions on this topic.
Comment on this article.
:
Figure
Horner syndrome. Image courtesy S Bhimji MD
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Publication Details
Author Information
Authors
A"liations
1 University of Missouri Hospital
2 University of Missouri
Publication History
Copyright
Copyright © 2022, StatPearls Publishing LLC.
This book is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/),
which permits use, duplication, adaptation, distribution, and reproduction in any medium or format, as long as you give appropriate credit to the original
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Publisher
:
StatPearls Publishing, Treasure Island (FL)
NLM Citation
Khan Z, Bollu PC. Horner Syndrome. [Updated 2022 May 8]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-.
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