Horner Syndrome

Horner syndrome, also known as Bernard Horner Syndrome or oculosympathetic palsy. This is a relatively rare disorder characterized by a constricted pupil (miosis), drooping of the upper eyelid (ptosis), absence of sweating of the face (anhidrosis), and sinking of the eyeball into the bony cavity that protects the eye (enophthalmos). These are the four classic signs of the disorder.

The congenital, and rarer, form of Horner syndrome is present at birth but the cause is not known. Most often, Horner syndrome is acquired as a result of some kind of interference with the sympathetic nerves serving the eyes. The underlying causes can vary enormously, from a snake or insect bite to a neck trauma made by a blunt instrument.

Horner's syndrome may be asymptomatic.

Symptoms:

• Inability to open eye fully on the affected side
• Loss of sweating on the affected side
• Facial flushing (if preganglionic lesion)
• Orbital pain/headache (if postganglionic lesion)

There may be other symptoms depending on the underlying cause e.g. head, neck or facial pain on the affected side if associated with carotid artery dissection.

Signs:

• Constricted pupil on the affected side, more apparent in a darkened room.
• Ipsilateral dry skin on the face due to loss of sweating.
• Ipsilateral partial ptosis (drooping of the upper eyelid) with possible paradoxical contralateral eyelid retraction.
• There may be apparent mild enophthalmos due to the sagging lid.
• There is increased amplitude of accommodation.
• Heterochromia irides may occur with congenital Horner's syndrome. The iris on the affected side remains blue whilst the other changes to brown. Pigmentation of the iris is under sympathetic control and is usually complete by the age of 2 years.

Causes of Horner syndrome may be classified as involving first-order, second-order, or third-order neuron lesions.

First-order neuron lesions that may give rise to the syndrome include the following:

• Arnold-Chiari malformation
• Basal meningitis (e.g. syphilis)
• Basal skull tumors
• Cerebral vascular accident (CVA)/Wallenberg syndrome (lateral medullary syndrome)
• Demyelinating disease (e.g. multiple sclerosis)
• Lesions in the hypothalamus or medulla
• Intrapontine hemorrhage
• Neck trauma (e.g. traumatic dislocation of cervical vertebrae or traumatic dissection of the vertebral artery) - 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
• Pituitary tumor
• Syringomyelia

Second-order neuron lesions that may give rise to Horner syndrome include the following:

• Pancoast tumor (tumor in the apex of the lung, most commonly squamous cell carcinoma)
• Birth trauma with injury to lower brachial plexus
• Cervical rib
• Aneurysm or dissection of the aorta
• Lesions of the subclavian or common carotid artery
• Central venous catheterization
• Trauma or surgical injury (e.g. due to radical neck dissection, thyroidectomy, carotid angiography, radiofrequency tonsil ablation, chiropractic manipulation, or coronary artery bypass grafting)
• Chest tubes
• Lymphadenopathy (e.g. Hodgkin disease, leukemia, tuberculosis, or mediastinal tumors)
• Mandibular tooth abscess
• Lesions of the middle ear (e.g. acute otitis media)
• Neuroblastoma

Third-order neuron lesions that may give rise to Horner syndrome include the following:

• Internal carotid artery dissection (associated with sudden ipsilateral face or neck pain)
• Raeder syndrome (paratrigeminal syndrome) - Oculosympathetic paresis and ipsilateral facial pain with variable involvement of the trigeminal and oculomotor nerves
• Carotid cavernous fistula
• Cluster or migraine headache
• Herpes zoster

Drugs that may cause symptoms similar to Horner syndrome include the following:

• Acetophenazine
• Alseroxylon
• Bupivacaine
• Butaperazine
• Carphenazine
• Chloroprocaine
• Chlorpromazine
• Deserpidine
• Diacetylmorphine
• Diethazine
• Ethopropazine
• Etidocaine
• Fluphenazine
• Guanethidine
• Influenza virus vaccine
• Levodopa
• Lidocaine
• Mepivacaine
• Mesoridazine
• Methdilazine
• Methotrimeprazine
• Oral contraceptives
• Perazine
• Prilocaine
• Procaine
• Prochlorperazine
• Promazine
• Promethazine
• Propoxycaine
• Reserpine
• Thioproperazine
• Thioridazine
• Trifluoperazine

Horner’s syndrome is diagnosed clinically. Pharmacological confirmation tests can be performed in subtle cases.

Presentation

Isolated Horner's: The patient, an acquaintance, or a health care provider may notice a difference in the palpebral aperture or pupillary size. Patients may also complain of ocular redness, nasal stuffiness and headache. Children with isolated Horner's syndrome may present when parents notice a difference in eye color or impaired facial flushing.

Non-isolated Horner’s: Horner's syndrome may accompany other neurologic or systemic deficits from disease processes.

Examination

Horner’s syndrome can be established clinically by an ocular examination. A targeted physical and neurological examination is a must to identify signs that may help localize the lesion and guide appropriate investigations.

Ocular signs:

• Eyelids - Patients have a mild (less than 2 mm) ptosis of upper lid and inverse ptosis of the lower lid (lower lid rests at a higher level than normal) which produces a decreased palpebral aperture compared to the fellow eye.
• Pupils: Patients have anisocoria (difference in the pupillary size) with the ptotic eye having the smaller pupil (miosis). The anisocoria is more prominent in the dark indicating pathology of the pupillary dilator. The smaller pupil takes a longer time to dilate when a bright source of light is moved away from the eye. This phenomenon is called dilation lag.
• Iris heterochromia (different colored irides) may be seen in children with congenital Horner’s.
• Extraocular movements may be affected in lesions of the brainstem or the cavernous sinus.

Other signs of sympathetic denervation include ipsilateral conjunctival injection, changes in accommodation and lower intraocular pressure.

Neurologic signs

Neurologic signs may be present depending on the site of lesion.

• Brainstem (bulbar) signs: ataxia, diplopia, nystagmus, lateralized weakness or numbness, hoarseness and dysphagia.
• Spinal cord (myelopathic) signs: sensory or motor abnomalities with a level, dysfunction of bowel or bladder movements, erectile dysfunction in men and spasticity.
• Brachial plexopathy: pain and weakness in the arm or hand; abnormalities can be confirmed by nerve conduction studies and electromyography of the involved extremity.
• Cranial neuropathy (single or multiple cranial nerves) can be produced by lesions in the cavernous sinus or base of skull.

Other signs:

• Anhidrosis: Variable degree of loss of sweating can be seen depending on the site of lesion. Central or preganglionic lesions tend to produce more noticeable anhidrosis. The sudomotor and vasomotor fibers to most of the face separate out at the superior cervical ganglion and anhidrosis is often not noticeable in postganglionic lesions.
• Harlequin sign: Impaired hemi-facial (or hemi-body) flushing seen in children with sympathetic denervation to the face.
• Cervical or abdominal mass may be seen in children with neuroblastoma.

Clinical diagnosis

Horner’s syndrome is diagnosed clinically by observing ptosis (of upper and lower lids), miosis of the ptotic eye and demonstration of dilation lag in the affected eye.

Pharmacologic tests
Topical Cocaine may be used to confirm Horner's syndrome in subtle cases. Cocaine blocks reuptake of the neurotransmitter norepinephrine from the synaptic cleft and will cause dilation of the pupil with intact sympathetic innervation.

One hour after instillation of two drops of 10% cocaine, the normal pupil dilates more than the Horner's pupil, thus increasing the degree of anisocoria. It is becoming increasingly difficult to obtain cocaine eye drops due to increased regulations.

Topical Apraclonidine is an alternative to topical cocaine to confirm Horner's syndrome. Apraclonidine is an alpha adrenergic agonist.

It causes pupillary dilation in the Horner's pupil due to denervation supersensitivity while producing a mild pupillary constriction in the normal pupil presumably by down-regulating the norepinephrine release at the synaptic cleft. A reversal of anisocoria after instilling two drops of 0.5% apraclonidine is suggestive of Horner's syndrome. 

Topical Hydroxyamphetamine is used to differentiate pre and postganglioninc Horner's. Hydroxyamphetamine causes a release of norepinephrine from intact adrenergic nerve endings causing pupillary dilation.

One hour after instillation of 1% hydroxyamphetamine eye drops, dilation of both pupils indicate a lesion of the 1st or 2nd order neuron. If the smaller pupil fails to dilate, it indicates a lesion of the 3rd order or postganglionic neuron.

The first step in the treatment of a patient with Horner’s syndrome is to perform appropriate studies to identify the cause.

Acute onset of painful Horner's should be considered a neurological emergency and subject should be evaluated for dissection of the internal carotid artery as described below. These patients are at increased risk for cerebral infarction.

Imaging is often indicated in new onset of Horner's syndrome unless it occurs in the setting of trauma or surgical manipulation.

High-yield sites of imaging can be identified based on accompanying signs and symptoms. These may include amongst others radiologic evaluation of brain, cervical spinal cord, cerebral vasculature, head, neck and thorax. Treatment depends on the etiology of Horner’s syndrome.

• Carotid artery dissection: Appropriate imaging modalities should be obtained emergently and may include MRI and MR angiography or CT angiography of the neck. Conventional angiogram remains the gold standard. Patients should be treated promptly by anticoagulation under the supervision of a neurologist.
• Neuroblastoma: Children with new Horner's syndrome without obvious cause such as trauma should be evaluated for systemic malignancy particularly neuroblastoma with the help of the pediatrician. They should be evaluated for neck and abdominal masses and tested for urinary catecholamine metabolites. Appropriate radiological evaluation of head, neck and chest should be obtained in consultation with the pediatrician.
• Brainstem or myelopathic lesions: Patients with brainstem or myelopathic signs require imaging of the brain and the spinal cord typically by MR imaging. Appropriate sequences should be ordered based on the suspected etiology.

Cavernous sinus and sellar region should be evaluated in patients with Horner's syndrome with ophthalmoparesis especially isolated sixth cranial nerve palsy. These patients should be under the care of a neurologist or neurosurgeon for treatment of the underlying causes.

• Thoracic malignancy: Isolated spontaneous onset Horner without additional neurologic signs should prompt imaging of the neck and thorax for lesions of the pulmonary apex or the paravertebral area. Contrasted CT or MR scans should be obtained based on the suspected etiology.
• Blepharoptosis: Once life-threatening conditions have been ruled out and the patient is stable, visually symptomatic ptosis can be managed surgically. The surgical approach varies on surgeon preference.

Since characteristically, the levator palpebrae function is normal in Horner's syndrome, surgery typically involves strengthening the action of the levator muscle. The approach may include either aponeurotic advancement or Müller's muscle-conjunctival resection.

Prevention strategies depend on the etiology of Horner’s syndrome. These may include prevention of trauma (especially head trauma), control of cardiovascular risk factors and smoking cessation. 

There are no direct complications of Horner syndrome itself.

However, there may be complications from the disease that caused Horner syndrome or from its treatment.