Ann P. Murchison
Jurij R. Bilyk

BASICS

DESCRIPTION

• Horner syndrome (HS) refers to the clinical triad of ptosis, miosis, and at times anhydrosis, which results from an interruption in the oculosympathetic pathway.

• May have iris heterochromia if congenital.

• Transient conjunctival hyperemia

• Congenital or acquired.

EPIDEMIOLOGY

Incidence

• Pediatric HS: 1.42 per 100,000 patients.

• Acquired adult HS: Unknown.

Prevalence

• Congenital HS: 1 in 6,250 births.

• Acquired adult HS: Unknown.

RISK FACTORS

• Head and neck trauma

• Brainstem or cervical spine pathology

• Neck or lung apex pathology, including benign tumors, malignancy, and inflammation

Genetics

A rare genetic form is likely an autosomal dominant trait. The vast majority of HS is sporadic and acquired from a localized abnormality.

GENERAL PREVENTION

None

PATHOPHYSIOLOGY

• First-order central sympathetic fibers descend from the hypothalamus through the midbrain and pons, and terminate in the intermediolateral cell column of the spinal cord (ciliospinal center of Budge) at the level of C8-T2.

• Second-order preganglionic sympathetic fibers exit the spinal cord at the level of T1, enter the cervical sympathetic chain near the pulmonary apex and the subclavian artery, then travel up the sympathetic chain and synapse in the superior cervical ganglion at the level of the bifurcation of the common carotid artery (C3–C4).

• Third-order postganglionic fibers exit the superior cervical ganglion, ascend along the internal carotid artery and enter the orbit through the optic canal and cavernous sinus/superior orbital fissure. Intraorbitally, the fibers travel with sensory nerves and arteries to innervate the iris dilator and Müller muscle.

ETIOLOGY

• First-order neuron lesions: Intracranial or cervical spine pathology.

• Second-order neuron lesions: Lung apex and neck to level of carotid bifurcation.

• Third-order neuron lesions: Carotid bifurcation to cavernous sinus.

• N.B.: Although migraine and cluster headaches may rarely present as HS, carotid dissection must be ruled out in any patient presenting with pain (including headache).

• N.B.: Cavernous sinus lesions rarely present as an isolated HS. Typically cranial neuropathy (e.g., abducens nerve palsy) is also present.

• N.B.: Orbital lesions never cause an isolated HS.

COMMONLY ASSOCIATED CONDITIONS

See Table 1 in “Online Resources”.

DIAGNOSIS

HISTORY

• By far, the most frequent complaint is new onset, unilateral ptosis.

• Patients rarely complain of visual problems secondary to miosis.

• Transient redness of the affected eye.

• Forehead anhydrosis is an infrequent complaint.

• Duration of symptoms is important to elicit.

• The most important symptom to obtain from the patient is the presence of any head, periorbital, or neck pain (sometimes described by the patient as a dull ache).

• Additional history may be obtained on directed questions

• Associated neurologic symptoms:

– Hemisensory loss

– Dysarthria

– Dysphagia

– Ataxia

– Vertigo

– Nystagmus

• Recent or distant head, neck, or chest trauma, including surgery.

• Any history of respiratory disease, including smoking.

• Any history of cancer.

PHYSICAL EXAM

• 1–3 mm of upper eyelid ptosis secondary to Müller muscle paresis

• Reverse ptosis (slight elevation) of the lower lid secondary to denervation of the inferior tarsal muscle. This finding is not always present, but is highly specific.

• Miosis

• Anisocoria that increases in the dark. Dilation lag is usually present (the affected pupil dilates slowly in a dark room).

• Anhydrosis is variable and difficult to test.

• Conjunctival hyperemia may be noted in the first 2 weeks of onset, but is usually a transient phenomenon.

• Iris heterochromia (hypopigmented iris) can be seen in congenital HS or in acquired pediatric HS (within a few months of birth).

DIAGNOSTIC TESTS & INTERPRETATION

Lab

Initial lab tests

• Initial lab studies are not necessary in the diagnosis of the HS.

• Lab tests may be considered depending on localization and suspected etiology:

– ACE and PPD placement if chest imaging is abnormal.

– Urine test (vanillylmandelic acid [VMA], homovanillic acid [HVA]) to rule out neuroblastoma in pediatric HS.

Follow-up & special considerations

Inspect old photographs for evidence of HS.

Imaging

Initial approach

• Correct imaging is critical in the management of HS.

• In many cases of HS, the history will provide important clues as to the etiology of the HS.

• Any acute HS (<4 weeks) presenting with head/neck pain or discomfort requires urgent imaging to rule carotid artery dissection.

• As a rule, the work-up of HS necessitates imaging from the level of the cavernous sinus (skull base) to the lung apex. Note that imaging of the brain above the skull base, as is usually done in routine brain CT and MRI, is unnecessary and inadequate.

• A combination of conventional imaging and angiography of the head and neck is recommended (MRI/MRA or CT/CTA).

• Extracranial Doppler ultrasonography is unreliable for diagnosing carotid artery dissection of the skull base.

• Chest CT or MRI to rule out apical lung mass.

• MRI of the thorax and abdomen to rule out neuroblastoma in children.

• Conventional arteriography is usually unnecessary (unless stenting of the carotid artery dissection is recommended in rare cases) and is contraindicated as a first imaging modality.

Follow-up & special considerations

• Multiple pharmacologic tests (cocaine, hydroxyamphetamine, phenylephrine, apraclonidine) are available for the diagnosis of HS. Note that many cannot be performed on the same day. The clinician should therefore carefully choose the test best suited for the patient. (See Table 2 in “Online Resources”)

• In general, cocaine and apraclonidine are the most useful and most frequently used agents.

– Should not be used in infants younger than 6 months without cardiopulmonary monitoring. Apraclonidine may cause lethargy, bradycardia, and respiratory depression in infants.

• Hydroxyamphetamine and dilute phenylephrine testing are impractical and usually unnecessary.

DIFFERENTIAL DIAGNOSIS

• Involutional ptosis with physiologic anisocoria. Both conditions are common and may coexist. In physiologic anisocoria, the amount of anisocoria will not change in bright and dim lighting, distinguishing it from that seen in HS.

• Cranial nerve III palsy. An incomplete CN-III paresis may present with ptosis. If anisocoria is present, the affected pupil is larger than the normal side.

• Holmes-Adie tonic pupil. The affected pupil is larger.

• Use of ipsilateral miotic (e.g., pilocarpine) or contralateral mydriatic agent

• Iris sphincter muscle damage (usually causes mild mydriasis). The most common cause is cataract surgery.

TREATMENT

MEDICATION

• Dependent upon the specific etiology.

• Carotid artery dissection.

– Antiplatelet or anticoagulant agents.

• Neuroblastoma

• Antineoplastic agents if secondary to neoplasia.

• Anti-inflammatory or anti-metabolite agents if inflammatory (e.g., sarcoidosis).

Geriatric Considerations

Cautionary use of topical cocaine and hydroxyamphetamine in elderly and in patients who may undergo urine testing in their occupation.

Pediatric Considerations

Cautionary use of topical cocaine, hydroxyamphetamine, or apraclonidine in infants or children.

Pregnancy Considerations

• Cocaine, hydroxyamphetamine, and apraclonidine are Class C agents.

• Cocaine and apraclonidine testing is contraindicated if breastfeeding due to high risk of significant adverse effects to infant/breast milk production.

• Caution is advised for topical hydroxyamphetamine during lactation.

ADDITIONAL TREATMENT

Issues for Referral

• Neurologic consultation for CVA, mass, meningitis, or medical management for carotid artery dissection

• Interventional radiology, vascular surgery, and/or neurosurgical consultation for carotid artery dissection or aneurysm for possible angioplasty and carotid artery stenting

• Oncology or infectious disease consultation for neoplastic or infectious etiology

• Pediatric oncology consultation for neuroblastoma

• Pulmonology consultation for management of sarcoidosis or lung mass.

• Oculoplastic consultation for ptosis repair

SURGERY/OTHER PROCEDURES

• Dependent upon specific etiology.

• Miosis is asymptomatic and does not require medical or surgical intervention.

• Eyelid repair

– Conjunctivomullerectomy for ptosis repair

IN-PATIENT CONSIDERATIONS

Dependent upon etiology.

ONGOING CARE

FOLLOW-UP RECOMMENDATIONS

Dependent upon etiology

DIET

Nutrition for children with neuroblastoma is important during therapy for adequate caloric intake for growth and development.

ADDITIONAL READING

• Almog Y, Gepstein R, Kesler A. Diagnostic value of imaging in Horner syndrome in adults. J Neuroophthalmol 2010;30(1):7–11.

• Chen PL, Chen JT, Lu DW, et al. Comparing efficacies of 0.5% apraclonidine with 4% cocaine in the diagnosis of Horner syndrome in pediatric patients. J Ocul Pharmacol Ther 2006;22(3):182–187.

• Smith SJ, Diehl N, Leavitt JA, et al. Incidence of pediatric Horner syndrome and the risk of neuroblastoma: A population-based study. Arch Ophthalmol 2010;128(3):324–329.

• Arnold M, Baumgartner RW, Stapf C, et al. Ultrasound diagnosis of spontaneous carotid dissection with isolated Horner syndrome. Stroke 2008;39(1):82–86.

• Mughal M, Longmuir R. Current pharmacologic testing for Horner syndrome. Curr Neurol Neurosci Rep 2009;9(5):384–389.

• Kadkhodayan Y, Jeck DT, Moran CJ, et al. Angioplasty and stenting in carotid dissection with or without associated pseudoaneurysm. AJNR Am J Neuroradiol 2005;26(9):2328–2335.

• Trobe JD. The evaluation of Horner syndrome. J Neuroophthalmol 2010;30(1):1–2.

• Koc F, Kavuncu S, Kansu T, et al. The sensitivity and specificity of 0.5% apraclonidine in the diagnosis of oculosympathetic paresis. Br J Ophthalmol 2005;89:1442–1444.

• Biousse V, D’Anglejan-Chatillon J, Touboul PJ, et al. Time course of symptoms in extracranial carotid artery dissections. A series of 80 patients. Stroke 1995;26:235–239.

• 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(2):93–96.

CODES

ICD9

• 337.09 Other idiopathic peripheral autonomic neuropathy

• 374.31 Ptosis of eyelid, paralytic

• 379.42 Miosis (persistent), not due to miotics

CLINICAL PEARLS

• HS in the presence of ipsilateral head, facial, or neck pain or discomfort requires urgent and correctly ordered imaging to rule out a carotid artery or vertebral artery dissection: CT/CTA or MRI/MRA of the head and neck.

• Imaging of the lung apex should be performed if other imaging is normal, but is not urgent.

• The anisocoria of HS is greater in dim light.

• “Reverse ptosis” of the lower lid is a helpful finding in the diagnosis of HS.

• Horner syndrome may be the first manifestation of neuroblastoma in the pediatric age group.

• Cocaine and apraclonidine are the most useful agents for pharmacologic testing of HS.

• Cocaine and apraclonidine should be used with caution in children younger than 6 months.

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