Horner Syndrome

Synonyms and related keywords: Bernard-Horner syndrome, Horner syndrome, Horner's syndrome, oculosympathetic paralysis, Raeder paratrigeminal syndrome, heterochromia irides, miosis, constricted pupil, partial ptosis, loss of hemifacial sweating, anhidrosis


INTRODUCTION

Background: Horner syndrome results from an interruption of the sympathetic nerve supply to the eye, and is characterized by the classic triad of miosis (ie, constricted pupil), partial ptosis, and loss of hemifacial sweating (ie, anhidrosis).

Pathophysiology: Sympathetic innervation to the eye consists of a 3-neuron arc. First-order fibers descend from the ipsilateral hypothalamus through the brain stem and cervical cord to T1/T2. These fibers synapse on ipsilateral preganglionic sympathetic fibers, exit the cord, travel to the sympathetic chain as second-order neurons to the superior cervical ganglion, and then synapse on postganglionic sympathetic fibers. The third-order neurons travel via the internal carotid artery to the orbit and innervate the (dilator) radial smooth muscle of the iris.

Postganglionic sympathetic fibers also innervate the muscle of Mueller within the eyelid. This muscle is responsible for initiating eyelid retraction during eyelid opening. Postganglionic sympathetic fibers responsible for facial sweating follow the external carotid artery to the sweat glands of the face. Interruption at any location along this pathway results in ipsilateral Horner syndrome.

Horner syndrome may result from the following conditions:

• A lesion of the primary neuron
• Brainstem stroke or tumor or syrinx of the preganglionic neuron
• Trauma to the brachial plexus
• Tumors (eg, Pancoast) or infection of the lung apex
• A lesion of the postganglionic neuron
• Dissecting carotid aneurysm
• Carotid artery ischemia
• Migraine
• Middle cranial fossa neoplasm

Frequency:

• In the US: Horner syndrome is uncommon.

Mortality/Morbidity: The implications of disease depend on the underlying cause.

Race: No known racial predilection exists.

Sex: No known sexual predilection exists.

Age: No known age predilection exists.

CLINICAL

History: Symptoms depend on the underlying cause.

• Patients may not be able to open the affected eye completely and may not sweat on same side of the face.

• Patients with preganglionic lesions may have facial flushing. This symptom (ie, harlequin effect) occurs in some patients as a result of physical exercise.

• Patients with postganglionic lesions may have ipsilateral orbital pain or a migrainelike headache.

• Raeder, a Norwegian ophthalmologist, described patients with a combination of orbital pain, miosis, and ptosis and termed it paratrigeminal syndrome.

• If this set of symptoms is associated with lesions of the cranial nerves (CN) III through VI on the ipsilateral side, suspect a mass lesion in the middle cranial fossa (eg, Raeder paratrigeminal syndrome, type I).
• A benign form characterized by episodic retrobulbar or orbital pain, with miosis and ptosis but without associated cranial nerve findings, is considered a migraine variant (ie, Raeder paratrigeminal syndrome, type II).

• When associated with carotid artery dissection, patients may present with ipsilateral head, neck, or facial pain.

Physical:

• Pupillary characteristics

• The pupil on the affected side may be round and constricted (ie, miosis).

• Patients may have a loss of the ciliospinal reflex (ie, afferent C2, C3). The pupil fails to dilate when the skin on back of the neck is pinched. Most authors, however, have found this test unreliable.

• Patients' anisocoria is greater in darkness. The affected pupil dilates more slowly than the normal pupil because the affected pupil lacks the pull of the dilator muscle (ie, dilation lag).

• Facial skin characteristics

• Patients have dry skin (ie, anhidrosis) on the same side of their face as the affected pupil.

• The pattern of a patient's inability to sweat may be helpful in localizing the lesion.

• If a patient has a lesion in the common carotid artery area, loss of sweating involves the entire side of the face.

• With lesions distal to the carotid bifurcation, the lack of sweating is confined to the medial aspect of the forehead and the side of the nose.

• Other findings

• Patients may have partial ptosis.

• Patients may have apparent enophthalmos. Contrary to some statements, true enophthalmos does not occur; the ptosis merely gives an illusion created by narrowing of the palpebral fissure, which results from weakness of the muscle of Mueller in both the upper lid (causing partial ptosis) and lower lid (causing slight elevation of lower eyelid).

• The amplitude of accommodation increases.

• Heterochromia irides may be present if the lesion occurred in a child younger than 2 years. The affected iris may remain blue when the other iris changes to brown. Iris pigmentation is under sympathetic control during development, which is completed by age 2 years. Heterochromia is uncommon in patients with Horner syndrome acquired later in life.

• Patients may have paradoxical contralateral eyelid retraction.

• Patients may experience a transient decrease in intraocular pressure and changes in tear viscosity.

• Patients may not have a horizontal eyelid fold or crease in the ptotic eye, especially those patients with congenital Horner syndrome.

• Patients may have red conjunctiva.

Causes: Horner syndrome can be congenital, acquired, or purely hereditary (autosomal dominant). The interruption of the sympathetic fibers may occur centrally (ie, between the hypothalamus and the fibers' point of exit from the spinal cord [C8 to T2]) or peripherally (ie, cervical sympathetic chain, superior cervical ganglion, along the carotid artery).

• Central causes (uncommon)

• Horner syndrome may be associated with lesions in the hypothalamus, medulla, or upper cervical cord. Wallenberg lateral medullary syndrome (stroke), demyelination, and rarely trauma or syringomyelia may result in Horner syndrome.

• It is rare in coma, but Horner syndrome may occur ipsilateral to a large cerebral hemorrhage that affects the thalamus. Ipsilateral Horner syndrome in a patient with laryngeal palsy suggests an intramedullary lesion.

• Horner syndrome occurring in association with spinal cord trauma suggests a high cervical cord lesion because it does not occur with lesions below T2 or T3.

• Peripheral causes

• Horner syndrome may be caused by lesions in the sympathetic chain, superior cervical ganglion, or along the carotid artery resulting from a Pancoast tumor (eg, apical bronchial carcinoma), trauma, or, rarely, from carotid dissection or carotid artery blow out, sarcoidosis, or tuberculosis in the cervical lymph nodes.

• Ipsilateral Horner syndrome and cranial neuropathy affecting cranial nerves IX through XII can be associated with an impending carotid artery blow out, a rare but fatal complication of lateral pharyngeal space infection.

• The common lesions that cause Horner syndrome interfere with preganglionic fibers as they course through the upper thorax. Virtually all lesions producing postganglionic sympathetic dysfunction are located intracranially or intraorbitally because the superior cervical ganglion is near the skull.

• Preganglionic Horner syndrome indicates a serious underlying pathology and is associated with a high incidence of malignancy. Common causes of acquired preganglionic Horner syndrome include trauma, aortic dissection, carotid dissection and Pancoast tumor, metastasis to cervical lymph nodes, and sarcoidosis or tuberculosis of cervical lymph nodes.

• Painful Horner syndrome suggests the possibility of silent internal carotid artery dissection.

• Postganglionic involvement has primarily benign causes (ie, usually a vascular headache). Common causes of postganglionic Horner syndrome include trauma, cluster migraine headache, and neck or thyroid surgery.

DIFFERENTIALS

Other Problems to be Considered:

Simple anisocoria
Senile miosis
Argyll Robertson pupil
Miotic drugs
Holmes-Adie pupil (contralateral)

WORKUP

Imaging Studies:

• Obtain a chest radiograph because apical bronchogenic carcinoma is the most common cause of Horner syndrome.

• Perform a head CT scan if stroke is suspected.

• In painful Horner syndrome, obtain a magnetic resonance angiography of the brain with cross-sectional imaging of neck to evaluate the possibility of carotid artery dissection.

Procedures:

• The following pharmacologic tests document the presence or absence of an ocular sympathetic lesion and identify the level of involvement (ie, preganglionic or postganglionic). Localizing the lesion is important because preganglionic lesions are associated with a higher incidence of malignancy that requires extensive investigations.

• Test to document ocular sympathetic lesion

• Agent - Cocaine (2%)

• Normal response - Dilatation

• Horner syndrome - No response

• Mechanism - Cocaine acts as an indirect sympathomimetic agent by inhibiting the reuptake of norepinephrine at the nerve ending.

• Remarks - To ensure accuracy, evaluate test results approximately 30 minutes after administering cocaine.

• Test to localize lesion (preganglionic or postganglionic)

• Agent - Hydroxyamphetamine (1%)

• Normal response - Dilation (preganglionic lesion)

• Horner syndrome - No response, indicates postganglionic lesion

• Mechanism - Hydroxyamphetamine promotes the release of stored endogenous norepinephrine from the postganglionic axon terminals into the neuromuscular junction at the iris dilator muscles, meaning that if the postganglionic cell and its terminals at the dilator muscles are intact, hydroxyamphetamine will release the stored norepinephrine and block norepinephrine uptake, and both actions will bring pupillary dilatation.

• Remarks - At least 24 hours must elapse between the cocaine and the hydroxyamphetamine tests because cocaine has the ability to inhibit the uptake of hydroxyamphetamine into the presynaptic vesicles, which will reduce accuracy.

TREATMENT

Medical Care: In general, appropriate treatment depends on the underlying cause. In many cases, no effective treatment is known. The goal of treatment is to eradicate the underlying disease process. Recognizing the presence of the syndrome and expedient referral to appropriate specialists are tantamount to early diagnosis.

Consultations: Patients may require consultations with appropriate specialists (eg, pulmonologists, neurologists, internists) to manage the underlying cause.

FOLLOW-UP

Prognosis:

• Prognosis depends on the underlying cause of the syndrome.

MISCELLANEOUS

Medical/Legal Pitfalls:

• Since malignancy is a prominent feature of recently diagnosed preganglionic Horner syndrome, patients may avoid an unnecessary extensive workup for carcinoma if the physician can document that the lesion is old or long-standing. To prove that a lesion is long-standing (ie, old), inspect old photographs of the patient that might show ptosis or anisocoria. If the affected iris is blue and the other iris is brown, the lesion most likely was present at birth, or at least during the first 2 years of life. This color asymmetry will not be applicable if both eyes are blue.

• Painful Horner syndrome should alert to the possibility of carotid artery dissection, and the patient should undergo further testing (ie, magnetic resonance imaging/angiography of the brain and neck) to exclude this possibility. Internal carotid artery dissection is life-threatening and carries the risk of the patient experiencing a disabling stroke.