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Horner Syndrome

Malvinder S Parmar, MB, MS, FRCP(C), FACP, Assistant Professor (VPT), Faculty of Medicine, University of Ottawa; Associate Professor, Department of Internal Medicine, Northern Ontario School of Medicine, Timmins and District Hospital, Canada

Updated: Jun 5, 2008

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).

Origin of Term

François Pourfour du Petit (1664-1741) first described the condition in 1727 in animal-experiments by cutting the intercostal nerves in the neck of dogs and noted that disturbances occurred in the eyes and face on the same side; this disproved earlier views of the cerebral origin of the intercostal nerves.¹ In 1838, the British physician Edward Selleck Hare (1812-1838) gave a  description of a man with a tumor in the cervical region. It was more thoroughly described by Claude Bernard in 1852.²  

A clinical report of the syndrome in a man shot through the throat was rendered in 1864 by the three American army physicians Silas Weir Mitchell (1829-1914), William Keen Jr. (1837-1932), and George Read Morehouse (1829-1905).³ Later, in 1869, Horner wrote an account of a woman aged 40 years who developed the classic manifestations of the syndrome.⁴  In 1958, DG Durham documented a family in which 5 persons in 2 generations of a family were affected.⁵ This rare genetic form is probably an autosomal dominant trait.

The term Horner syndrome is commonly used in English-speaking countries, whereas the term Bernard-Horner syndrome is common in France.

von Passow syndrome is an association of Horner syndrome with heterochromia iridis.⁶

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 (In one study, 33% of patients with brainstem lesions demonstrated Horner syndrome.⁷ )
• Trauma to the brachial plexus
• Tumors (eg, Pancoast) or infection of the lung apex (See Lung Cancer.)
• A lesion of the postganglionic neuron
• Dissecting carotid aneurysm (In one study, 44% (65/146) of patients with internal extracranial carotid artery dissections had painful Horner syndrome, which remained isolated in half the cases (32/65).⁸ )
• Carotid artery ischemia
• Migraine
• Middle cranial fossa neoplasm

Frequency

United States

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 the 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.⁹
  • 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. Get relevant CME at Dissections of Brain-Supplying Arteries.

Physical

• Pupillary characteristics
  • The pupil on the affected side may be round and constricted (ie, miosis). Get related CME at Examining the Eyes of an Older Person.
  • 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 finding unreliable.
  • Patients' anisocoria is greater in darkness. The affected pupil dilates more slowly than the normal pupil does 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 is 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, subclavian and internal jugular vein cannulation, or, rarely, from carotid dissection or carotid artery blow out, following chest tube insertion for pleural fluid drainage,¹⁰ 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.

Differential Diagnoses

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

• Topical cocaine test  
  • Agent - Cocaine (2-4%)
  • 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. Hence, mydriasis occurs in the normal pupil but not in the norepinephrine-deficient Horner pupil.
  • Remarks - To ensure accuracy, evaluate test results approximately 30 minutes after administering cocaine.
  • Disadvantage - Controlled substance, lack of availability, its metabolites may occur in urine
• Topical apraclonidine test - The current test of choice  
  • Agent - Apraclonidine (0.5%)^11,12
  • Normal response - Relative miosis
  • Horner syndrome - Relative mydriasis and reversal of ptosis
  • Mechanism - Apraclonidine is a weak alpha1-agonist and a strong alpha2-agonist. In Horner syndrome, there is upregulation of alpha1-receptors that increases apraclonidine sensitivity. The denervation supersensitivity results in pupillary dilatation and lid elevation on the abnormal side but no response or mild miosis on the normal side from alpha2-activity following apraclonidine.
  • Remarks - Apraclonidine is readily available and adequately sensitive with sensitivity of 87%.¹² Its mydriatic effect on abnormal pupil makes for easier interpretation.
  • In acute cases, false-negative test results may occur since the effect of apraclonidine is dependent on up-regulation of alpha1-receptors that may take 5-8 days. Hence, a negative test result, especially in acute settings, does not exclude Horner syndrome and a cocaine test should be considered.

Test to localize lesion (preganglionic or postganglionic) 

• Hydroxyamphetamine test
  • 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.

Get relevant CME and Diagnosis and Management in Neuro-Ophthalmology.

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

Medicolegal 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 is not 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.
• A negative apraclonidine test result does not exclude Horner, especially in acute cases, as up-regulation of alpha1-receptors takes between 5-8 days. A cocaine test should be performed in such cases to exclude Horner syndrome.

References

1. du Petit FP. Mémoire dans lequel il est démontré que les nerfs intercostaux fournissent des rameaux que portent des esprits dans les yeux. Paris, Mém: Hist Acad Roy Sci; 1727;1-19.

2. Bernard C. Des phénomènes oculo-pupillaires produits par la section du nerf sympathique cervical: ils sont indépendants des phénomènes vasculaires calorifiques de la tête. Comptes rendus de l'Académie des sciences, Paris. 1852;55:381-88.

3. Weir Mitchell S, Keen Jr W, Morehouse GR. Gunshot Wounds and Other Injuries of Nerves. Philadelphia: Lippincott; 1864. Reprinted, San Francisco: Norman Publishing; 1989.

4. Horner JF. Über eine Form von Ptosis. Klinische Monatsblätter für Augenheilkunde, Stuttgart. 1869;7:193-8.

5. Durham DG. Congenital hereditary Horner's syndrome. AMA Arch Ophthalmol. Nov 1958;60(5):939-40. [Medline].

6. von Passow A. Okulare Paresen im Symptomenbilde des "Status dysraphicus", zugleich ein Beitrag zur Ätiologie der Sympathikusparese (Horner-Syndrom und Heterochromia iridis). Münchener medizinische Wochenshrift. 1934;74:1243-9.

7. Krasnianski M, Georgiadis D, Grehl H, Lindner A. [Correlation of clinical and magnetic resonance imaging findings in patients with brainstem infarction]. Fortschr Neurol Psychiatr. May 2001;69(5):236-41. [Medline].

8. Biousse V, Touboul PJ, D'Anglejan-Chatillon J, Lévy C, Schaison M, Bousser MG. Ophthalmologic manifestations of internal carotid artery dissection. Am J Ophthalmol. Oct 1998;126(4):565-77. [Medline].

9. Raeder JG. Brain. Oxford: 1924:47;149-158.

10. Rombolá CA, Atance PL, Honguero Martínez AF. Claude Bernard-Horner Syndrome as a Rare Complication of Postoperative Pleural Drainage. Arch Bronconeumol. 2008;44:116-7. [Medline].

11. Morales J, Brown SM, Abdul-Rahim AS, Crosson CE. Ocular effects of apraclonidine in Horner syndrome. Arch Ophthalmol. Jul 2000;118(7):951-4. [Medline].

12. Koc F, Kavuncu S, Kansu T, Acaroglu G, Firat E. The sensitivity and specificity of 0.5% apraclonidine in the diagnosis of oculosympathetic paresis. Br J Ophthalmol. Nov 2005;89(11):1442-4. [Medline].

13. Adams RD, Victor M. Eye signs in neurologic diagnosis. In: Principles of Neurology. 5^th ed. New York: McGraw-Hill, Inc; 1993:375-9.

14. Biousse V, Touboul PJ, D'Anglejan-Chatillon J, Levy C, Schaison M, et al. Ophthalmologic manifestations of internal carotid artery dissection. Am J Ophthalmol. Oct 1998;126(4):565-77. [Medline].

15. Birch C. Horner. In: Names We Remember 56 Eponymous Medical Biographies. Kent, England: Ravenswood, Beckenham; 70-72.

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17. Dziewas R, Konrad C, Drager B, Evers S, Besselmann M, Ludemann P, et al. Cervical artery dissection--clinical features, risk factors, therapy and outcome in 126 patients. J Neurol. Oct 2003;250(10):1179-84. [Medline].

18. Lee JH, Lee HK, Lee DH, Choi CG, Kim SJ, Suh DC. Neuroimaging strategies for three types of Horner syndrome with emphasis on anatomic location. AJR Am J Roentgenol. Jan 2007;188(1):W74-W81. [Medline].

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22. Morris JG, Lee J, Lim CL. Facial sweating in Horner's syndrome. Brain. Sep 1984;107 ( Pt 3):751-8. [Medline].

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Keywords

Bernard syndrome, Bernard-Horner syndrome, Horner syndrome, Horner's syndrome, Horner’s oculopupillary syndrome, Horner oculopupillary syndrome, Horner’s sign, Horner sign, Horner's symptom complex, Horner symptom complex, Horner's triad, Horner triad, Hutchinson’s syndrome, Hutchinson syndrome, Mitchell’s syndrome III, Mitchell syndrome, oculosympathetic paralysis, Raeder paratrigeminal syndrome, Raeder’s paratrigeminal syndrome, heterochromia irides, von Passow’s syndrome, von Passow syndrome, miosis, constricted pupil, partial ptosis, hemifacial sweat, hemifacial anhidrosis, facial sweating, facial flushing, harlequin effect  

Contributor Information and Disclosures

Author

Malvinder S Parmar, MB, MS, FRCP(C), FACP, Assistant Professor (VPT), Faculty of Medicine, University of Ottawa; Associate Professor, Department of Internal Medicine, Northern Ontario School of Medicine, Timmins and District Hospital, Canada
Malvinder S Parmar, MB, MS, FRCP(C), FACP is a member of the following medical societies: American College of Physicians, American Society of Nephrology, Canadian Medical Association, Ontario Medical Association, and Royal College of Physicians and Surgeons of Canada
Disclosure: Nothing to disclose.

Medical Editor

Philip Schulman, MD, Chief, Medical Oncology, Department of Medicine, Memorial Sloan-Kettering Cancer Center; Clinical Professor, Department of Medicine, New York University School of Medicine
Philip Schulman, MD is a member of the following medical societies: American Association for Cancer Research, American College of Physicians, American Society of Clinical Oncology, American Society of Hematology, and Medical Society of the State of New York
Disclosure: celgene Honoraria Speaking and teaching; Amgen Honoraria Speaking and teaching; genetech/idec Honoraria Speaking and teaching

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Benjamin Movsas, MD is a member of the following medical societies: American College of Radiology, American Radium Society, American Society for Therapeutic Radiology and Oncology, and American Society of Clinical Oncology
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Rajalaxmi McKenna, MD, FACP, Consulting Staff, Department of Medicine, Southwest Medical Consultants, SC, Good Samaritan Hospital, Advocate Health Systems
Rajalaxmi McKenna, MD, FACP is a member of the following medical societies: American Society of Clinical Oncology, American Society of Hematology, and International Society on Thrombosis and Haemostasis
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Chief Editor

Jules E Harris, MD, Visiting Professor of Medicine, Division of Hematology/Medical Oncology, Department of Internal Medicine, University of Arizona College of Medicine at Tucson; Consulting Staff, Arizona Cancer Center
Jules E Harris, MD is a member of the following medical societies: American Association for Cancer Research, American Association for the Advancement of Science, American Association of Immunologists, American Society of Clinical Oncology, American Society of Hematology, and Central Society for Clinical Research
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