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Horner’s syndrome (also called oculosympathetic paresis, or Horner syndrome) comprises a constellation of clinical signs including the classic triad of ptosis, miosis, and anhidrosis. It results from a lesion to the sympathetic pathway that supplies the head and neck region. The cause of Horner’s syndrome varies with the site of the lesion. Prompt evaluation is necessary to detect and treat potentially life-threatening conditions.

Disease Entity

Horner's Syndrome. ICD-9 337.9, ICD-10 G90.2

Epidemiology

In a population based study of Horner’s syndrome in the pediatric age group, the incidence of Horner’s syndrome was estimated to be 1.42 per 100 000 patients younger than 19 years, with a birth prevalence of 1 in 6250 for those with a congenital onset.

Pathophysiology

Horner's syndrome results from a lesion to the sympathetic pathways that supply the head and neck, including the oculosympathetic fibers.

Relevant anatomy

The pupil is innervated by sympathetic and parasympathetic fibers. Pupillary dilation is mediated by a three-neuron sympathetic pathway that originates in the hypothalamus.

First order (central) neuron

The first order (central) neuron descends caudally from the hypothalamus to the first synapse in the cervical spinal cord (C8-T2 level-also called the ciliospinal center of Budge). The descending sympathetic tract is in close proximity to other tracts and nuclei in the brainstem.

Second order (preganglionic) neuron

The second order (preganglionic) neuron destined for the head and neck exits the spinal cord and travels in the cervical sympathetic chain through the brachial plexus, over the pulmonary apex and synapses in the superior cervical ganglion. The superior cervical ganglion is located near the angle of the mandible and bifurcation of the common carotid artery.

Third order (postganglionic) neuron

The third order (postganglionic) neuron for the orbit enters the cranium within the adventitia of the internal carotid artery into the cavernous sinus. Here, the oculosympathetic fibers exit the internal carotid artery in close proximity to the trigeminal ganglion and the sixth cranial nerve and join the 1st division of the trigeminal nerve to enter the orbit.

The fibers (long ciliary nerve) innervate the dilator muscles of the iris and the smooth muscle (Müller’s muscle) in the upper and lower eyelid (inferior retractors).
The vasomotor and sudomotor fibers to the face exit the superior cervical ganglion and ascend in the external carotid artery.
Pupillary constriction is produced by parasympathetic (cholinergic) fibers that travel with the third cranial (oculomotor) nerve.

Etiology

The etiology of Horner’s syndrome varies with the patient age and site of lesion. The etiology remains unknown in 35-40% of cases.

Central (first order neuron) Horner’s

Central (first order neuron) Horner’s: These include lesions of the hypothalamus, brainstem and spinal cord such as stroke (classically the lateral medullary syndrome), demyelination (such as multiple sclerosis), neoplasms (such as glioma), or other processes such as a syrinx (syringomyelia or syringobulbia).

Preganglionic (second order neuron) Horner’s

Preganglionic (second order neuron) Horner’s: These include lesions of the thoracic outlet (cervical rib, subclavian artery aneurysm), mediastinum (mediastinal tumors), pulmonary apex (Pancoast's tumor), neck (thyroid malignancies) or the thoracic spinal cord (trauma) or surgical procedures in this region including radical neck dissection, jugular vein cannulation, thoracoscopy or mediastinoscopy, chest tube placement and other thoracic surgical procedures.

Third order neuron or postganglionic lesion

Third order neuron or postganglionic lesion: These include lesions of the superior cervical ganglion (trauma, radical neck dissection or jugular vein ectasia), lesions of the internal carotid artery (ICA) in the neck and skull base (dissection, thrombosis, invasion by tumors or iatrogenic from endarterectomy or stenting, base of skull malignancies), lesions of ICA in the cavernous sinus (thrombosis, aneurysm, inflammation or invasive tumors) and lesions of the sellar and parasellar regions (invasive pituitary tumors, metastatic tumors, paratrigeminal tumors). Other causes include cluster headaches.

Children

In children, trauma (birth trauma or neck trauma) is the most common cause of Horner’s syndrome.

Other causes

Other causes include surgical trauma, neuroblastoma, brainstem lesions (such as vascular malformations, glioma and demyelination) and carotid artery thrombosis.

Primary prevention

Prevention strategies depend on the etiology of Horner’s syndrome. These may include prevention of trauma (especially head trauma), control of cardiovascular risk factors, and smoking cessation.

Diagnosis

Horner’s syndrome is a clinical diagnosis. Pharmacological confirmation tests can be performed in subtle cases.

Presentation

Isolated Horner's

Isolated Horner's: The patient, an acquaintance, or a health care provider may notice a difference in the palpebral aperture or pupillary size. Patients may also complain of ocular redness, nasal stuffiness and headache. Children with isolated Horner's syndrome may present when parents notice a difference in eye color, pupil size, or impaired facial flushing.

Non-isolated Horner's

Non-isolated Horner’s: Horner's syndrome may accompany other neurologic or systemic deficits from disease processes listed above.

Examination

Horner’s syndrome can be established clinically by an ocular examination. A targeted physical and neurological examination is a must to identify signs that may help localize the lesion and guide appropriate investigations.

Ocular signs

Eyelids: patients have a mild (less than 2 mm) ptosis of upper lid and inverse ptosis of the lower lid (lower lid rests at a higher level than normal), which produces a decreased palpebral aperture compared to the fellow eye.
Pupils: Patients have anisocoria (difference in the pupillary size) with the ptotic eye having the smaller pupil (miosis). The anisocoria is more prominent in the dark, indicating pathology of the pupillary dilator. The smaller pupil takes a longer time to dilate when a bright source of light is moved away from the eye. This phenomenon is called dilation lag.
Iris heterochromia (different colored irides) may be seen in children with congenital Horner’s.
Extraocular movements may be affected in lesions of the brainstem or the cavernous sinus.
Other signs of sympathetic denervation include ipsilateral conjunctival injection, changes in accommodation and lower intraocular pressure.

Neurologic signs

Neurologic signs may be present depending on the site of lesion

Brainstem (bulbar) signs: ataxia, diplopia, nystagmus, lateralized weakness or numbness, hoarseness and dysphagia.
Spinal cord (myelopathic) signs: sensory or motor abnormalities with a spinal cord level, e.g. dysfunction of bowel or bladder movements, erectile dysfunction in men and spasticity.
Brachial plexopathy: pain and weakness in the arm, or hand; abnormalities can be confirmed by nerve conduction studies and electromyography of the involved extremity.
Cranial neuropathy (single or multiple cranial nerves) can be produced by lesions in the cavernous sinus or base of skull.

Other signs

Anhidrosis: Variable degree of loss of sweating can be seen depending on the site of the lesion. Central or preganglionic lesions tend to produce more noticeable anhidrosis. The sudomotor and vasomotor fibers to most of the face separate out at the superior cervical ganglion and anhidrosis is often not noticeable in postganglionic lesions.
Harlequin sign: Impaired hemi-facial (or hemi-body) flushing seen in children with sympathetic denervation to the face.
Cervical or abdominal mass may be seen in children with neuroblastoma.

Clinical diagnosis

Horner’s syndrome is diagnosed clinically by observing ptosis (of upper and lower lids), miosis of the ptotic eye and demonstration of dilation lag in the affected eye, and anhidrosis on the same side as the ptosis and/or mitosis.

Pharmacologic tests

Topical Cocaine may be used to confirm Horner's syndrome in subtle cases. Cocaine blocks reuptake of the neurotransmitter norepinephrine from the synaptic cleft and will cause dilation of the pupil with intact sympathetic innervation. One hour after instillation of two drops of 10% cocaine, the normal pupil dilates more than the Horner's pupil, thus increasing the degree of anisocoria. It is becoming increasingly difficult to obtain cocaine eye drops due to increased regulations.
Topical Apraclonidine is an alternative to topical cocaine to confirm Horner's syndrome. Apraclonidine is an alpha adrenergic agonist. It causes pupillary dilation in the Horner's pupil due to denervation supersensitivity while producing a mild pupillary constriction in the normal pupil presumably by down-regulating the norepinephrine release at the synaptic cleft. A reversal of anisocoria after instilling two drops of 0.5% apraclonidine is suggestive of Horner's syndrome. Be aware: you can get a false-negative result in acute cases of Horner's syndrome because upregulation of alpha-1 adrenergic receptors on the dilator papillae muscle is not present immediately after the injury (but is estimated to occur between 5-8 days).
Topical Hydroxyamphetamine is used to differentiate pre and postganglioninc Horner's. Hydroxyamphetamine causes a release of norepinephrine from intact adrenergic nerve endings causing pupillary dilation. One hour after instillation of 1% hydroxyamphetamine eye drops dilation of both pupils indicate a lesion of the 1st or 2nd order neuron. If the smaller pupil fails to dilate it indicates a lesion of the 3rd order or postganglionic neuron.

Differential diagnosis

Anisocoria:

Essential anisocoria
Adie pupil (long-standing)
Argyll-Robertson pupil
Chronic anterior uveitis
Pupillary sphincter tear
Unilateral use of miotics or mydriatics
Third nerve palsy

Ptosis:

Aponeurotic ptosis
Ocular myasthenia
Third nerve palsy (ptotic eye has the larger pupil)
Congenital ptosis

Management

Acute onset of painful Horner's should be considered a neurological emergency and subject should be evaluated for dissection of the internal carotid artery as described below. These patients are at increased risk for cerebral infarction.

The first step in the management of a patient with Horner’s syndrome is to perform appropriate studies to identify the cause. Imaging is often indicated in new onset Horner's syndrome unless it occurs in the setting of trauma or surgical manipulation. High-yield sites of imaging can be identified based on accompanying signs and symptoms. These may include amongst others radiologic evaluation of brain, cervical spinal cord, cerebral vasculature, head, neck and thorax. Treatment depends on the etiology of Horner’s syndrome.

Carotid artery dissection: Appropriate imaging modalities should be obtained emergently and may include MRI and MR angiography or CT angiography of the neck. Conventional angiogram remains the gold standard. Patients should be treated promptly by anticoagulation under the supervision of a neurologist.
Neuroblastoma: Children with new Horner's syndrome without obvious cause such as trauma should be evaluated for systemic malignancy particularly neuroblastoma with the help of the pediatrician. They should be evaluated for neck and abdominal masses and tested for urinary catecholamine metabolites. Appropriate radiological evaluation of head, neck and chest should be obtained in consultation with the pediatrician.
Brainstem or myelopathic lesions: Patients with brainstem or myelopathic signs require imaging of the brain and the spinal cord typically by MR imaging. Appropriate sequences should be ordered based on the suspected etiology. Cavernous sinus and sellar region should be evaluated in patients with Horner's syndrome with ophthalmoparesis especially isolated sixth cranial nerve palsy. These patients should be under the care of a neurologist or neurosurgeon for treatment of the underlying causes.
Thoracic malignancy: Isolated spontaneous onset Horner without additional neurologic signs should prompt imaging of the neck and thorax for lesions of the pulmonary apex or the paravertebral area. Contrasted CT or MR scans should be obtained based on the suspected etiology.

Blepharoptosis: Once life-threatening conditions have been ruled out and the patient is stable, visually symptomatic ptosis can be managed surgically. The surgical approach varies on surgeon preference. Since characteristically the levator palpebrae function is normal in Horner's syndrome, surgery typically involves strengthening the action of the levator muscle. The approach may include either aponeurotic advancement or Müller's muscle- conjunctival resection.

Follow up

Follow up of Horner’s syndrome depends on the etiology of Horner’s syndrome

Prognosis

Prognosis depends on the etiology of Horner’s syndrome

Additional Resources

AAO, Basic and Clinical Science Course. Section 5: Neuro-ophthalmology, 2015-2016.

References

Smith SJ, Diehl N, Leavitt JA, Mohney BG. Incidence of pediatric Horner syndrome and the risk of neuroblastoma: a population-based study. Arch Ophthalmol. 201;128(3):324-9
Kardon, R. Anatomy and physiology of the autonomic nervous system. In: Walsh and Hoyt Clinical Neuro-ophthalmology, 6th ed, Miller, NR, Newman, NJ, Biousse, V, Kerrison, JB (Eds), Williams & Wilkins, Baltimore 2005. p.649.
Morris JG, Lee J, Lim CL. Facial sweating in Horner's syndrome. Brain. 1984;107(3):751-8
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(4):651-9.
de Bray JM, Baumgartner R, Guillon B, Pautot V, Dziewas R, Ringelstein EB, Sturzenegger M, Garnier P, Ducrocq X, Saudeau D, Neau JP, Larrue V, Vuillier F, Boulliat J, Verret JM, Verny C, Dubas F. Isolated Horner's syndrome may herald stroke. Cerebrovasc Dis. 2005;19(4):274-5
Glatt HJ, Putterman AM, Fett DR. Muller’s muscle-conjunctival resection procedure in the treatment of ptosis in Horner’s syndrome. Ophthalmic Surg 1990;21:93–6

Horner Syndrome

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