AUTHOR AND EDITOR INFORMATION

Section 1 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• References

Background

Horner syndrome refers to a constellation of signs produced when sympathetic innervation to the eye is interrupted. Lesions at any point along the sympathetic pathway may result in Horner syndrome. Signs found in all patients, regardless of the level of interruption include mild-to-moderate ptosis owing to denervation of the sympathetically controlled Müller muscle, slight elevation of the lower lid (upside-down ptosis) due to denervation of the lower lid muscle analogous to Müller muscle in the upper lid, and miosis and dilation lag, where pupillary dilation after psychosensory stimuli is slower in the affected pupil than the unaffected pupil.

Depending on the level of the lesion, impaired flushing and sweating may be found ipsilaterally. Anhydrosis affects the ipsilateral side of the body with central, first-order neuron lesions. Lesions affecting second-order neurons may cause anhydrosis of the ipsilateral face. With postganglionic lesions occurring after vasomotor and sudomotor fibers have branched off the sympathetic chain, anhydrosis is either absent or limited to an area above the ipsilateral brow. The pupils react normally to light and accommodation. Iris heterochromia (with the affected eye being hypopigmented) is seen in congenital Horner syndrome or Horner syndrome that occurs in children younger than 2 years. Iris heterochromia also may occur in long-standing Horner syndrome.

Pathophysiology

First-order central sympathetic fibers arise from the posterolateral hypothalamus, descend uncrossed through the mid brain and pons, and terminate in the intermediolateral cell column of the spinal cord at the level of C8-T2 (ciliospinal center of Budge). Second-order preganglionic pupillomotor fibers exit the spinal cord at the level of T1, enter the cervical sympathetic chain, where they are in close proximity to the pulmonary apex and the subclavian artery.

The fibers ascend through the sympathetic chain and synapse in the superior cervical ganglion at the level of the bifurcation of the common carotid artery (C3-C4). Postganglionic pupillomotor fibers exit the superior cervical ganglion and ascend along the internal carotid artery. Shortly after the postganglionic fibers leave the superior cervical ganglion vasomotor and the sudomotor fibers branch off, they travel along the external carotid artery to innervate the blood vessels and sweat glands of the face. The pupillomotor fibers ascending along the internal carotid artery enter the cavernous sinus. Then, the fibers leave the carotid plexus briefly to join the abducens nerve (VI) in the cavernous sinus and enter the orbit through the superior orbital fissure along with the ophthalmic branch of the trigeminal nerve (V1) via the long ciliary nerves. Then, the long ciliary nerves innervate the iris dilator and Müller muscle.

Mortality/Morbidity

Depends on specific etiology

CLINICAL

Section 3 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• References

History

Obtaining a careful history is very helpful in the localization of lesions causing Horner syndrome.

• First-order neuron lesions may be associated with signs and symptoms such as hemisensory loss, dysarthria, dysphagia, ataxia, vertigo, and nystagmus.
• Second-order neuron lesions may be preceded by trauma and may be accompanied by facial, neck, axillary, shoulder or arm pain, cough, hemoptysis, history of thoracic or neck surgery, history of chest tube or central venous catheter placement, or neck swelling.
• Symptoms associated with third-order neuron lesions include diplopia from sixth nerve palsy, numbness in the distribution of the first or second division of the trigeminal nerve, and pain.
• The presence, absence, and/or location of anhydrosis is an important localizing sign that may be elicited from the history.
• Although Horner syndrome is commonly an incidental finding related to a benign cause, it occasionally may be a manifestation of a serious and life-threatening disorder. Careful direction of the history to rule out such life-threatening disorders is of the utmost importance (see Causes).

Physical

• Important aspects of the physical examination include the following:
• • Measurement of pupillary diameter in dim and bright light and their reactivity to light and accommodation
  • Examination of the upper lids for ptosis
  • Examination of the lower lids for upside-down ptosis (eg, position of the lower lid with respect to the inferior limbus)
  • Extraocular movements
  • Biomicroscopic examination of the pupillary margin and iris structure and color
  • Confrontational visual field testing and testing of facial sensation
  • Observation for the presence of nystagmus, facial swelling, lymphadenopathy, or vesicular eruptions

Causes

• First-order neuron lesions
• • Arnold-Chiari malformation
  • Basal meningitis (eg, syphilis)
  • Basal skull tumors
  • Cerebral vascular accident (CVA)/Wallenberg syndrome (lateral medullary syndrome)
  • Demyelinating disease (eg, multiple sclerosis)
  • Intrapontine hemorrhage
  • Neck trauma (eg, traumatic dislocation of cervical vertebrae, traumatic dissection of the vertebral artery)
  • Pituitary tumor
  • Syringomyelia
• Second-order neuron lesions
• • Pancoast tumor (tumor in the apex of the lung - most commonly squamous cell carcinoma)
  • Birth trauma with injury to lower brachial plexus
  • Cervical rib
  • Aneurysm/dissection of aorta
  • Subclavian or common carotid artery
  • Central venous catheterization
  • Trauma/surgical injury (radical neck dissection, thyroidectomy, carotid angiography, coronary artery bypass graft)
  • Chest tubes
  • Lymphadenopathy (Hodgkin disease, leukemia, tuberculosis, mediastinal tumors)
  • Mandibular tooth abscess
  • Lesions of the middle ear (eg, acute otitis media)
  • Neuroblastoma
• Third-order neuron lesions
• • Internal carotid artery dissection (associated with sudden ipsilateral face and/or neck pain)
  • Raeder syndrome (paratrigeminal syndrome) - Oculosympathetic paresis and ipsilateral facial pain with variable involvement of the trigeminal and oculomotor nerves
  • Carotid cavernous fistula
  • Cluster/migraine headaches
  • Herpes zoster
• Drugs (may cause symptoms similar to Horner syndrome and may affect any region)
• • Acetophenazine
  • Alseroxylon
  • Bupivacaine
  • Butaperazine
  • Carphenazine
  • Chloroprocaine
  • Chlorpromazine
  • Deserpidine
  • Diacetylmorphine
  • Diethazine
  • Ethopropazine
  • Etidocaine
  • Fluphenazine
  • Guanethidine
  • Influenza virus vaccine
  • Levodopa
  • Lidocaine
  • Mepivacaine
  • Mesoridazine
  • Methdilazine
  • Methotrimeprazine
  • Oral contraceptives
  • Perazine
  • Prilocaine
  • Procaine
  • Prochlorperazine
  • Promazine
  • Promethazine
  • Propoxycaine
  • Reserpine
  • Thioproperazine
  • Thioridazine
  • Trifluoperazine

DIFFERENTIALS

Section 4 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

Third nerve palsy
Unilateral use of miotics
Unilateral use of mydriatics
Adie pupil
Iris sphincter muscle damage

WORKUP

Section 5 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• References

Lab Studies

• Lab studies in general do not play a role in the diagnosis and management of Horner syndrome. However, depending on the localization and suspected etiology, lab tests one may consider, in conjunction with appropriate medical consultation, include the following: CBC, fluorescent treponemal antibody absorption (FTA-ABS) test, Venereal Disease Research Laboratory (VDRL) test, purified protein derivative (PPD) placement, and/or urine test (ie, vanillylmandelic acid [VMA], homovanillic acid [HVA]) to rule out neuroblastoma in pediatric Horner syndrome.

Imaging Studies

• Imaging studies may be ordered in conjunction with appropriate medical and/or surgical consultation depending on the localization and suspected etiology. Such studies may include MRI/MRA, angiography, extracranial Doppler ultrasound, and/or chest x-ray.

Other Tests

• Pharmacologic testing is very helpful in the diagnosis of Horner syndrome and localization of lesions causing Horner syndrome.
• Cocaine (4% or 10% solution)
• • Cocaine inhibits the re-uptake of norepinephrine from the synaptic cleft. Two drops of 4% or 10% cocaine solution are instilled into each eye.
  • Cocaine instilled in an eye with intact sympathetic innervation causes the pupil to dilate. A sympathetically denervated pupil dilates poorly to cocaine, regardless of the level of the sympathetic interruption because of the absence of endogenous norepinephrine in the synapse.
  • The maximum response is seen 40-60 minutes after instillation of the drops. Postcocaine anisocoria greater than 0.8 mm is sufficient to diagnose Horner syndrome.
  • The disadvantages of cocaine drops are as follows: they are difficult to obtain because they must be made at a compounding pharmacy, they are relatively expensive, and they can give equivocal results.
• Apraclonidine (0.5% or 1%)
• • Apraclonidine is a practical and reliable alternative to cocaine.
  • Apraclonidine is an ocular hypotensive agent. It is a weak, direct-acting alpha-1 receptor agonist. Apraclonidine has little to no effect on a normal pupil.
  • Patients with Horner syndrome have denervation supersensitivity of the iris dilator muscle. Therefore, the pupil in the affected eye dilates in response to apraclonidine. Reversal of anisocoria occurs after bilateral instillation of apraclonidine.
• Hydroxyamphetamine 1% (Paredrine)
• • The localization of a lesion causing Horner syndrome may be aided by the use of 1% hydroxyamphetamine solution. Hydroxyamphetamine may distinguish a postganglionic third-order neuron lesion from a presynaptic second-order or first-order neuron lesion. Hydroxyamphetamine stimulates the release of norepinephrine from presynaptic postganglionic nerve terminals.
  • Two drops of 1% hydroxyamphetamine solution are instilled into each eye. Note that results of this test will be inaccurate if performed within 24-48 hours of the cocaine test.
  • Hydroxyamphetamine instilled into an eye with Horner syndrome with intact postganglionic fibers (ie, first- or second-order neuron lesions) dilates the pupil to an equal or greater extent than the normal pupil. An eye with Horner syndrome with damaged postganglionic fibers (third-order neuron lesions) does not dilate as well as the normal pupil after hydroxyamphetamine drops.

TREATMENT

Section 6 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• References

Medical Care

Medical care is dependent upon the particular etiology.

Surgical Care

Surgical care is dependent upon the particular etiology. Potential surgical care includes neurosurgical care for aneurysm-related Horner syndrome and vascular surgical care for etiologies such as carotid artery dissection/aneurysm.

Consultations

Neurologic or neuro-ophthalmic consultation may be considered. Interventional radiologic consultation in cases of suspected carotid artery dissection. Neurosurgical consultation should be considered in cases of suspected aneurysm. Surgical or oncologic consultation is dependent upon the particular etiology.

FOLLOW-UP

Section 7 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• References

Further Inpatient Care

• Dependent upon etiology

Further Outpatient Care

• Dependent upon etiology

In/Out Patient Meds

• Dependent upon etiology

Transfer

• Dependent upon etiology

Deterrence/Prevention

• Dependent upon etiology

Prognosis

• Dependent upon etiology

MISCELLANEOUS

Section 8 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• The principal medical/legal pitfall in the management of Horner syndrome is related to misdiagnosis of a serious or life-threatening etiology. Life-threatening causes of Horner syndrome should first be ruled out with a pertinent history and physical examination. Appropriate consultation and/or imaging should be obtained without delay if a serious underlying cause is suspected.

Special Concerns

• Horner syndrome in the presence of pain merits special consideration.
• Horner syndrome in the presence of axial, shoulder, scapula, arm, or hand pain may be indicative of compression by an apical lung tumor (Pancoast tumor).
• Horner syndrome in the presence of acute-onset, ipsilateral facial or neck pain may indicate carotid artery dissection. Carotid artery dissection may be caused by cardiovascular disease, arteriopathy (fibromuscular dysplasia, collagen disorders), or trauma (even minor trauma such as from quick head turns). If carotid artery dissection is suspected, especially in the presence of signs or symptoms of retinal ischemia, urgent neuroimaging (MRI/MRA) should be obtained along with neurologic consultation.
• Postganglionic Horner syndrome associated with ipsilateral headache has several causes. Patients with spontaneous carotid artery dissection may present with Horner syndrome and ipsilateral headache. Patients with cluster headaches may develop ipsilateral Horner syndrome during an acute attack. The term Raeder paratrigeminal syndrome has been used to describe patients, usually middle-aged males, who have Horner syndrome and daily unilateral head pain. The pain in the original Raeder syndrome is trigeminal pain associated with hypesthesia or anesthesia in the distribution of the trigeminal nerve (cranial nerve V). Pain related to Raeder syndrome can be distinguished from that of cluster headaches or carotid disease in that these conditions occur without impairment of trigeminal nerve function.
• Horner syndrome may be the first manifestation of neuroblastoma.

REFERENCES

Section 9 of 9

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• References

• Albert DM, Jakobiec FA. Principles and Practice of Ophthalmology. 1994;4:2473-4.
• American Academy of Ophthalmology. Basic and Clinical Science Course: Neuro-ophthalmology. 1999-2000;5:97-99, 109-111.
• Fraunfelder, FT. Drug-Induced Ocular Side Effects and Drug Interactions. 1996;4:553.
• Freedman KA, Brown SM. Topical apraclonidine in the diagnosis of suspected Horner syndrome. J Neuroophthalmol. Jun 2005;25(2):83-5. [Medline].
• Gutman I, Levartovski S, Goldhammer Y, et al. Sixth nerve palsy and unilateral Horner''s syndrome. Ophthalmology. Jul 1986;93(7):913-6. [Medline].
• Loewenfeld I. The Pupil: Anatomy, Physiology and Clinical Applications. 1993;2:1131-1177.
• Mokhtari F, Massin P, Paques M, et al. Central retinal artery occlusion associated with head or neck pain revealing spontaneous internal carotid artery dissection. Am J Ophthalmol. Jan 2000;129(1):108-9. [Medline].
• Roy FH. Ocular Syndromes and Systemic Diseases. 1989.

Article Last Updated: Mar 25, 2006