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Horner Syndrome
Deborah A. Lardner, DO, DTM&H
Michael Passafaro, DO, DTM&H, FACEP, FACOEP
image BASICS
DESCRIPTION
  • Horner syndrome presents as a classic triad of ipsilateral miosis, eyelid ptosis, and/or anhidrosis of the face and neck (with iris heterochromia in children).
  • It is caused by the interruption of sympathetic nerve supply to the head, neck, and eye.
    • Central or preganglionic lesion (complete syndrome): 1st- or 2nd-order neuron
    • Peripheral postganglionic lesion (incomplete syndrome, no anhidrosis): 3rd-order neuron
  • System(s) affected: nervous, skin/exocrine
  • Synonym(s): Bernard-Horner syndrome; Bernard syndrome; Horner's syndrome; cervical sympathetic syndrome; oculosympathetic syndrome; oculosympathetic paralysis; oculosympathetic deficiency; oculosympathetic paresis
EPIDEMIOLOGY
  • Predominant age: none
  • Predominant sex: male = female
Incidence
Unknown
Prevalence
Unknown
ETIOLOGY AND PATHOPHYSIOLOGY
  • Constellation of signs produced when sympathetic innervation to the head, neck, and eye is interrupted somewhere along the three-neuron arc
    • Absence of innervation of iris dilator and Müller muscles leads to miosis and slight ptosis, respectively.
    • Sympathetic innervation also controls sweat glands; interruption causes anhidrosis.
  • Oculosympathetic pathway
    • 1st-order neuron: Sympathetic nerve fibers originate in the hypothalamus, descend through the brainstem, and synapse at the ciliospinal center (of Budge) located at approximately the C8-T2 levels of the spinal cord.
    • 2nd-order neuron: exits the spinal column at the T1 level primarily, arches over the apex of the lung and under the subclavian artery, ascending to the superior cervical ganglion at the level of the carotid bifurcation and angle of the jaw
    • 3rd-order neuron: ascends along the adventitia of the internal carotid artery, through the cavernous sinus in proximity to cranial nerve [CN] VI, and joins CN VI to innervate the iris dilator muscle and Müller muscle in the eye
  • Sympathetic fibers innervating sweat glands and vasodilatory muscles branch off before the cervical sympathetic ganglion traveling along the external carotid artery, so distal lesions will not result in anhidrosis.
  • Lesions anywhere along this pathway will lead to ipsilateral Horner syndrome.
  • Idiopathic (40%), congenital, or acquired
  • Best classified by which order neuron is affected and by age (pediatric vs. adult)
  • 1st-order neuron (13%)
    • Arnold-Chiari malformation
    • Basal meningitis (e.g., syphilis)
    • Basal skull tumors
    • Cerebral vascular accident: lateral medullary (Wallenberg) syndrome
    • Cervical cord trauma
    • Demyelinating disease (multiple sclerosis)
    • Intrapontine hemorrhage
    • Neck trauma
    • Pituitary tumor
    • Syringomyelia
    • Unintended subdural placement of lumbar epidural catheter
  • 2nd-order neuron (44%)
    • Aneurysm/dissection of aorta
    • Central venous catheterization
    • Chest tubes
    • First rib fracture
    • Lymphadenopathy (Hodgkin, leukemia, tuberculosis, mediastinal tumors, sarcoid)
    • Mandibular tooth abscess
    • Neurofibromatosis types I and II
    • Pancoast tumor or infection of lung apex
    • Proximal common carotid artery dissection
    • Trauma/surgical injury
  • 3rd-order neuron lesions (43%)
    • Carotid cavernous fistula or other pathology
    • Carotid endarterectomy or carotid artery stenting
    • Cluster headaches
    • Internal carotid artery dissection
    • Herpes zoster
    • Lesions of the middle ear (acute otitis media)
    • Lyme disease
    • Nasopharyngeal cancer
    • Tonsillectomy
    • Raeder paratrigeminal syndrome
  • Drugs: acetophenazine, alseroxylon, bupivacaine, butaperazine, carphenazine, chloroprocaine, deserpidine, diacetylmorphine, diethazine, ethopropazine, etidocaine, guanethidine, influenza virus vaccine, levodopa, lidocaine, mepivacaine, mesoridazine, methdilazine, methotrimeprazine, oral contraceptives, perazine, prilocaine, procaine, prochlorperazine, promazine, propoxycaine, reserpine, thioproperazine, thioridazine, trifluoperazine
Genetics
Rare autosomal dominant inheritance
RISK FACTORS
  • Most common: apical bronchogenic carcinoma (Pancoast tumor) in smokers
  • Aneurysm of the carotid or subclavian artery
  • Injuries to the carotid artery high in the neck
  • Dissection of the carotid arteries
  • Carotid artery occlusion
    • 15% of patients with carotid artery occlusion develop ipsilateral Horner syndrome.
    • May occur without evidence of cerebral ischemia, neck injuries, or operative procedures
  • Cluster headaches
    • 20% have an ipsilateral Horner syndrome.
Pediatric Considerations
2nd-order neuron lesion is the most common etiology: birth trauma to neck and shoulder, chest surgery, neuroblastoma (paraspinal), and vascular anomalies of the carotid arteries.
COMMONLY ASSOCIATED CONDITIONS
  • Wallenberg syndrome
  • Pancoast tumor
  • C8 radiculopathy
image DIAGNOSIS
PHYSICAL EXAM
  • Measure pupillary diameter in dim and bright light and reactivity to light and accommodative response:
    • Anisocoria is greatest in dark, with affected pupil failing to dilate.
    • Redilation (after light is removed) may lag 15 to 20 seconds on the affected side.
  • Examine the upper lids for ptosis (<2 mm).
  • Examination of the lower lids for “upside-down ptosis”: elevation of lower lid due to Müller muscle weakness
    • Illusion of enophthalmos secondary to narrowing of palpebral fissure
  • Ipsilateral impaired flushing may be found.
  • Loss of ciliospinal reflex. Pinching the skin on back of the neck normally produces ipsilateral pupil dilation (unreliable).
  • Biomicroscopic exam of the papillary margin and iris structure and color
    • In congenital Horner syndrome, long-standing Horner syndrome, or Horner syndrome that occurs in children <2 years: Iris shows reduced pigmentation, blue-gray, and mottling of the affected eye (heterochromia iridis) because formation of iris pigment early in life is under sympathetic control.
  • Observe for the presence of nystagmus, facial swelling, lymphadenopathy, or vesicular eruptions.
  • Ophthalmoparesis, specifically CN VI palsy with Horner syndrome, is suggestive of cavernous sinus lesion.
  • Neurologic and chest exams for associated physical findings
P.497

DIFFERENTIAL DIAGNOSIS
  • Neurologic diseases
  • 3rd nerve palsy
  • Unilateral use of miotics
  • Unilateral use of mydriatics
  • Adie tonic pupil
  • Iris sphincter muscle damage
DIAGNOSTIC TESTS & INTERPRETATION
Initial Tests (lab, imaging)
CBC, fluorescent treponemal antibody absorption test, venereal disease research laboratory, purified protein derivative; vanillylmandelic acid, homovanillic acid to rule out neuroblastoma in pediatric patients
  • Chest x-ray if patient is a smoker (apical bronchogenic carcinoma)
  • CT/MRI/MRA of the brain, chest, and spinal cord
    • If painful, order MRI/MRA to evaluate for carotid artery dissection emergently.
  • Ultrasound may be considered for evaluation of internal carotid artery
Pediatric Considerations
In a child of any age without contributory history, MRI brain, neck, and chest to exclude a mass lesion (1)[B]
DIAGNOSTIC PROCEDURES/OTHER
  • Confirmation of Horner syndrome
    • Topical 0.5% apraclonidine (2)[A],(3,4)[B]
    • 4-10% topical cocaine
      • Used to confirm diagnosis of Horner syndrome but will not identify location of lesion
      • If the diagnosis is clear clinically, this test is not required.
      • A normal pupil will dilate. The miotic pupil in Horner syndrome (regardless of location of lesion) will not dilate or will dilate poorly after 45 minutes because of the absence of norepinephrine at the nerve endings of the 3rd-order neuron (2)[A].
      • Positive test is anisocoria of ≥1 mm.
      • Cocaine blocks the reuptake of norepinephrine by the neuron.
  • Distinguishing a 3rd-order neuron disorder from a 1st- or 2nd-order neuron disorder:
    • Topical 1% hydroxyamphetamine (2)[A]
      • If there is a 1st- or 2nd-order neuron lesion, dilation will take place.
      • Failure of the pupil to dilate, or poor dilation, indicates a 3rd-order neuron lesion (positive when anisocoria increases by ≥1 mm).
      • No pharmacologic test exists to differentiate between a 1st- and 2nd-order neuron lesion.
      • Hydroxyamphetamine causes release of endogenous norepinephrine stored in the postganglionic neuron.
      • Alternative test: 1% topical pholedrine
  • Must wait >24 hours between the cocaine and hydroxyamphetamine tests.
Pediatric Considerations
Due to transsynaptic degeneration in children, the hydroxyamphetamine test is not reliable.
Test Interpretation
  • Brainstem lesion
  • Massive hemisphere lesion
  • Cervical cord lesion
  • Root lesion
  • Sympathetic chain lesion
image TREATMENT
GENERAL MEASURES
  • Horner syndrome in itself does not produce any disability or necessarily require treatment.
  • Treat the underlying etiology.
  • Search for a tumor or other compressive lesion.
MEDICATION
Carotid artery dissection: Pharmacologic treatment options include thrombolysis, antithrombotic therapy with anticoagulation, or antiplatelet therapy. No randomized control trials have compared these treatment options (5)[C].
ISSUES FOR REFERRAL
  • Neurologic, neuro-ophthalmic, oculoplastic
  • Neurologic or vascular surgery: interventional in cases of suspected carotid artery dissection or aneurysm
  • Neurosurgery, surgical oncology, oncology, or radiotherapy consultation depends on the particular etiology.
SURGERY/OTHER PROCEDURES
  • Surgical care depends on etiology.
  • Consider ptosis repair surgery (oculoplastics).
image ONGOING CARE
PROGNOSIS
  • Postganglionic: usually benign
  • Central and preganglionic: poorer prognosis
REFERENCES
1. Al-Moosa A, Eggenberger E. Neuroimaging yield in isolated Horner syndrome. Curr Opin Ophthalmol. 2011;22(6):468-471.
2. Antonio-Santos AA, Santo RN, Eggenberger ER. Pharmacological testing of anisocoria. Expert Opin Pharmacother. 2005;6(12):2007-2013.
3. 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(11):1442-1444.
4. 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.
5. Patel RR, Adam R, Maldjian C, et al. Cervical carotid artery dissection: current review of diagnosis and treatment. Cardiol Rev. 2012;20(3):145-152.
Additional Reading
&NA;
  • Ahmadi O, Saxena P, Wilson BK, et al. First rib fracture and Horner's syndrome: a rare clinical entity. Ann Thorac Surg. 2013;95(1):355.
  • Almog Y, Gepstein R, Kesler A. Diagnostic value of imaging in Horner syndrome in adults. J Neuroophthalmol. 2010;30(1):7-11.
  • Bazari F, Hind M, Ong YE. Horner's syndrome—not to be sneezed at. Lancet. 2010;375(9716):776.
  • Davagnanam I, Fraser CL, Miszkiel K, et al. Adult Horner's syndrome: a combined clinical, pharmacological, and imaging algorithm. Eye (Lond). 2013;27(3):291-298.
  • Kong YX, Wright G, Pesudovs K, et al. Horner syndrome. Clin Exp Optom. 2007;90(5):336-344.
  • Lee JH, Lee HK, Lee DH, et al. Neuroimaging strategies for three types of Horner syndrome with emphasis on anatomic location. AJR Am J Roentgenol. 2007;188(1):W74-W81.
  • Lyrer PA, Brandt T, Metso TM, et al. Clinical import of Horner syndrome in internal carotid and vertebral artery dissection. Neurology. 2014;82(18): 1653-1659.
  • Mahoney NR, Liu GT, Menacker SJ, et al. 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):651-659.
  • Martin TJ. Horner's syndrome, pseudo-Horner's syndrome, and simple anisocoria. Curr Neurol Neurosci Rep. 2007;7(5):397-406.
  • Reede DL, Garcon E, Smoker WR, et al. Horner's syndrome: clinical and radiographic evaluation. Neuroimaging Clin N Am. 2008;18(2):369-385.
Codes
&NA;
ICD10
  • G90.2 Horner's syndrome
  • S14.5XXA Injury of cervical sympathetic nerves, initial encounter
Clinical Pearls
&NA;
  • Horner syndrome triad: ipsilateral miosis, eyelid ptosis, and anhidrosis caused by a lesion of the oculosympathetic pathway
  • Ptosis is mild, usually <2 mm.
  • Red flags: If associated with pain, suspect central or preganglionic lesion.
  • Confirm the diagnosis clinically with topical cocaine to the affected eye.
  • Use hydroxyamphetamine to differentiate which order neuron is affected.
  • Order imaging studies based on history and physical and hydroxyamphetamine testing.
  • Horner syndrome in the presence of acute-onset, ipsilateral facial or neck pain: Consider carotid artery dissection until proven otherwise.