Horners syndrome

What is Horners syndrome? 

Horners syndrome is an interruption of the sympathetic supply to the eye, resulting in the classic triad of ptosis, miosis, and anhydrosis.

Horner syndrome is the clinical triad of ipsilateral ptosis, miosis, and sometimes facial anhidrosis. Disruption of any of the three neurons in the oculosympathetic pathway (first-order, second-order, or third-order) can cause Horner syndrome.

Synonyms

• Oculosympathetic paresis
• Raeder paratrigeminal syndrome: Horner syndrome of the third-order neuron associated with pain in the trigeminal nerve distribution

Epidemiology & Demographics

Congenital or acquired

Physical Findings & Clinical Presentation

• •Ptosis is usually mild. It results from loss of sympathetic tone to Müller muscle, which contributes approximately 2 mm of upper eyelid elevation. Weakness of the corresponding muscle in the lower eyelid causes it to elevate slightly. This combination causes narrowing of the palpebral fissure. Levator function of the eyelid is preserved.
• •Miosis results from loss of sympathetic innervation to the iris dilator muscle. The affected pupil reacts normally to bright light and accommodation. Anisocoria is greater in dim light.
  • 1.Dilation lag: Horner pupil dilates more slowly than the normal pupil when lights are dimmed (20 vs. 5 sec) because it dilates passively as a result of relaxation of the iris sphincter.
• •Presence of facial anhidrosis is variable and depends on the site of injury. It occurs with lesions affecting first-order or second-order neurons.
• •Congenital Horner syndrome may result in heterochromia. The affected eye has a lighter-colored iris.
• •Acute cases may also present with facial flushing, conjunctival injection, and nasal stuffiness from the loss of sympathetic vasoconstriction.

What causes Horners syndrome?

Disruption of the ipsilateral sympathetic innervation to the eye and face.

Lesions can damage any of the three neurons in the oculosympathetic pathway. First-order neuron lesions are least common but are usually caused by pathology in the hypothalamus, brain stem, or cervicothoracic spinal cord.

Second-order neuron lesions are often caused by disease involving the cervicothoracic spinal cord, lung apex, or anterior neck.

Third-order neuron lesions are usually seen with disease in the internal carotid artery, skull base, cavernous sinus, or orbital apex. Location is often suggested by the presence of associated findings. Vascular disease and neoplasm must be considered.FIG. E1

Anatomy of sympathetic pathways to the eye.

The sympathetic innervation of the eye consists of three neurons connected in a series: First-order neurons, second-order neurons, and third-order neurons.

The first-order neurons (central neurons) extend from the posterior hypothalamus to the C8 to T2 level of the spinal cord.

The second-order neurons (preganglionic neurons) leave the spinal cord and travel over the lung apex, around the subclavian artery, and along the carotid artery to the superior cervical ganglion.

The third-order neurons (postganglionic neurons) diverge and take two paths: Those to the pupil and lid muscles travel along the internal carotid artery through the cavernous sinus to reach the orbit; those to the facial sweat glands travel with the external carotid artery to the face.

Lesions in any of these neurons cause Horner syndrome and distinct associated physical signs.

One large study found that 65% of patients with Horner syndrome had an identifiable cause, 13% had a first-order neuron lesion, 44% had a second-order neuron lesion, and 43% had a third-order neuron lesion.

Mechanical:

• •Syringomyelia
• •Trauma
• •Tumors: Benign, malignant head and neck cancers (thyroid, apical lung, mediastinal)
• •Cervical rib

Vascular (ischemia, hemorrhage or arteriovenous malformation):

• •Brain stem lesion: Commonly occlusion of the posterior inferior cerebellar artery but other arteries may be responsible (vertebral; superior, middle or inferior lateral medullary arteries; superior or anterior inferior cerebellar arteries)
• •Carotid artery aneurysm, dissection, arteritis: Can also be from injury to other major vessels (internal carotid artery, subclavian artery, ascending aorta)
• •Jugular venous ectasia
• •Cavernous sinus thrombosis
• •Cluster headache, migraine

Miscellaneous:

• •Idiopathic
• •Congenital
• •Demyelination (multiple sclerosis)
• •Infection (apical tuberculosis, herpes zoster, Lyme disease)
• •Myelitis
• •Pneumothorax
• •Iatrogenic (angiography, internal jugular/subclavian catheter, chest tube, neck or upper thoracic surgery, epidural spinal anesthesia)

Differential Diagnosis

Causes of anisocoria (unequal pupils):

• •Normal variant
• •Mydriatic use, medications
• •Prosthetic eye
• •Prior eye surgery, trauma
• •Iritis
• •Acute angle-closure glaucoma
• •Adie tonic pupil
• •Third nerve palsy

Causes of ptosis are described in Section II.

How is this condition diagnosed?

Horners syndrome is diagnosed by

• History
• physical examination
• pharmacologic testing
• imaging

Pharmacologic Testing

These medications may not be readily available. Pharmacologic testing should not delay evaluation in acute, painful, or traumatic cases or in patients with a history of malignancy.

• •Topical cocaine test: Confirms diagnosis (drops increase anisocoria by dilating normal pupil but not Horner pupil).
• •Topical apraclonidine test: Confirms diagnosis (drops reverse anisocoria by causing dilation of Horner pupil and slight constriction of normal pupil). Less reliable than topical cocaine in acute Horner syndrome.
• •Topical hydroxyamphetamine test: Distinguishes first- and second-order neuron lesions from third-order sympathetic lesions (drops dilate normal pupil and first- or second-order Horner pupil, but not third-order Horner pupil). Testing must be delayed >48 hr after topical cocaine or apraclonidine testing.

• In a patient has a right Horner syndrome with right miosis and ptosis (middle row). 45 min after installation of cocaine drops into each eye (top row), the Horner pupil fails to dilate, but the normal pupil dilates, markedly aggravating the anisocoria and confirming the diagnosis of Horner syndrome. 45 min after installation of apraclonidine drops into each eye (performed on a different day than the cocaine test; bottom row), the right Horner pupil dilates, but there is no response in the normal pupil, thus reversing the anisocoria and also confirming the diagnosis of Horner syndrome. Cocaine eyedrops block the reuptake of norepinephrine at the myoneural junction of the iris dilator, causing the pupil to dilate unless norepinephrine is absent because of sympathetic denervation. Apraclonidine eyedrops have no effect on normal pupils, but after sympathetic denervation from Horner syndrome, the affected pupil is supersensitive to their effect. Apraclonidine may also cause elevation of the lid in Horner syndrome (bottom row), although only the response of the pupil is used when interpreting the test.

Finding (Reference)	Sensitivity (%)	Specificity (%)	LIKELIHOOD RATIO IF FINDING IS
Present	Absent
Detecting Horner Syndrome
Anisocoria ≥1 mm after topical cocaine	95	99	96.8	0.1
Reversal of anisocoria after topical apraclonidine	95	90-95	14.0	0.1
Diagnosing First- or Second-Order Nerve Lesion in Horner Syndrome
Small pupil dilates with topical hydroxyamphetamine (Paredrine)	83-92	79-96	9.2	0.2
Small pupil fails to dilate with dilute phenylephrine	88	79	4.2	NS
Asymmetric facial sweating	53	78	NS	0.6

Imaging Studies

• •One approach is to image the entire oculosympathetic pathway with an MRI of the brain to the upper chest and an MRA of the neck (or CT/CTA if acute presentation or MR not possible)
• •Other approaches suggest using results of pharmacologic testing, as well as accompanying signs and symptoms to guide imaging
• •MRI brain: Brain stem (diplopia, eye movement abnormalities, vertigo, ataxia, lateral medullary syndrome); cavernous sinus (sixth nerve palsy)
• •MRI cervical and upper thoracic spinal cord: Sensory changes/weakness of extremities, bowel/bladder dysfunction
• •MRI/MRA or CTA neck: Carotid artery dissection (acute Horner syndrome with face or neck pain)
• •CT chest and neck: Evaluate lung apex, perivertebral areas, mediastinum if symptoms do not localize to the central nervous system; brachial plexus lesion (arm/hand pain or weakness)

How is Horners syndrome treated?

• •Treatment depends on underlying cause.
• •Ptosis can be surgically corrected or treated with medication (phenylephrine drops).

Referral

Ophthalmologist for pharmacologic testing to confirm diagnosis and localize lesion

 Pearls & Considerations

• •May be the presentation of a life-threatening condition. Horner syndrome presenting acutely or associated with head/neck pain, trauma, or history of malignancy should be evaluated urgently.
• •Normal variant anisocoria:
  • 1.Occurs in 20% of people
  • 2.Usually <1 mm difference between pupils
  • 3.Pupils are round and display a normal, brisk constriction and dilation response to light
• •Infants with Horner syndrome may present with Harlequin sign, contralateral hemifacial flushing

Suggested Readings

• Davagnanam I., et al.: Adult Horner’s syndrome: a combined clinical, pharmacological and imaging algorithm. Eye 2013; 27: pp. 291.
• Gross J.R., et al.: An approach to anisocoria. Curr Opin Ophthalmol 2016; 27: pp. 486.
• Martin T.J.: Horner syndrome: a clinical review. ACS Chem Neurosci 2018; 9: pp. 177.