Skip to content

BASICS

Description

  • Neurological syndrome caused by lesion of sympathetic pathway.
  • Classic triad: ipsilateral miosis, ptosis, and anhidrosis.
  • Iris heterochromia seen in congenital cases (children).
  • Also known as Bernard syndrome.

Epidemiology

  • Pediatric incidence: 1.42 per 100,000 in patients <19 years.
  • Birth prevalence for congenital cases: 1 in 6,250.
  • Adult incidence unknown.

ETIOLOGY AND PATHOPHYSIOLOGY

Pathway

  • Sympathetic innervation disruption to the eye and face.
  • Ptosis: loss of sympathetic tone to Müller muscle causing mild eyelid droop (<2 mm).
  • Miosis: impaired pupillary dilation; affected pupil smaller, especially in dim light.
  • Anhidrosis: loss of facial/neck sweating; helps localize lesion level.

Causes in Adults

  • Arnold-Chiari malformation, basal meningitis (e.g., syphilis)
  • Cerebrovascular accident, Wallenberg syndrome
  • Cervical trauma, spondylosis, demyelinating disease (MS)
  • Tumors: Pancoast tumor, thyroid, mediastinum, nasopharyngeal
  • Carotid artery dissection, aneurysm, central venous catheterization
  • Thoracic outlet syndrome, cluster headaches
  • Infectious: herpes zoster, Lyme disease
  • Post-surgical: neck/chest procedures

Causes in Children

  • Birth trauma, brachial plexus injury (most common)
  • Neuroblastoma
  • Brainstem glioma
  • Vascular anomalies
  • Surgical trauma
  • Idiopathic

Genetics

  • Rare autosomal dominant inheritance.

RISK FACTORS

  • Recent head, neck, thoracic trauma
  • Smoking (Pancoast tumor)
  • Known vascular aneurysms
  • History of neck or thoracic surgery
  • Cluster headache history

DIAGNOSIS

History

  • Onset (acute vs chronic)
  • Visual symptoms: blurred vision, diplopia, field loss
  • Pain: ipsilateral head, neck, face
  • Trauma or surgery history
  • Associated neurological symptoms
  • Presence of sweating or flushing abnormalities
  • In children: note iris color changes (heterochromia)
  • Red flag: acute-onset with ipsilateral pain—consider carotid artery dissection

Physical Exam

  • Measure anisocoria in bright and dim light (anisocoria more pronounced in dim light).
  • Sluggish pupillary dilation (dilation lag) in affected eye.
  • Mild upper eyelid ptosis (<2 mm) and possible lower lid "reverse ptosis".
  • Ipsilateral conjunctival injection, nasal congestion.
  • Biomicroscopic exam: iris color, structure, nystagmus.
  • Full cranial nerve exam.
  • Neck exam for masses, trauma.
  • Neurologic and chest exam.

Differential Diagnosis

  • Physiologic anisocoria (<1 mm variation)
  • Third nerve palsy
  • Myasthenia gravis
  • Pharmacologic causes (miotics/mydriatics, various drugs)

Diagnostic Tests

  • Labs: CBC, syphilis serology (FTA-ABS, VDRL), PPD, urinary VMA/HVA (pediatric neuroblastoma screen).
  • Imaging:
  • Chronic: MRI head/neck/chest with contrast + MRA for carotids and chest apex.
  • Acute/unable to tolerate MRI: CT head/neck/chest + CTA; follow with MRI if negative.
  • Consider carotid angiogram if equivocal.
  • Pediatric: MRI brain, neck, chest ± abdomen if neuroblastoma suspected.
  • Pregnancy: MRI considered safe; gadolinium contrast category C.

Pharmacological Testing

  • Apraclonidine 0.5% drops: reverses anisocoria by dilating affected pupil due to denervation hypersensitivity (positive test = affected pupil dilates).
  • Cocaine 4-10% drops: blocks norepinephrine reuptake, dilates normal pupil but not affected one (positive test = lack of dilation in affected eye).
  • Hydroxyamphetamine 1% drops: differentiates lesion localization.
  • Dilation of both pupils = first- or second-order neuron lesion.
  • No dilation of affected pupil = third-order neuron lesion.

TREATMENT

General Measures

  • Exclude life-threatening causes urgently.
  • Address ptosis for cosmesis/visual impairment if persistent >12 months.

Medications

  • Carotid artery dissection: thrombolysis, anticoagulation, or antiplatelet therapy.
  • Mild ptosis: oxymetazoline 0.1% ophthalmic drops raise eyelid by ~1–1.3 mm; onset 2 hours, lasts ~8 hours.
  • Side effects: eye discomfort, headache, dry eye.

Referral

  • Neurosurgery, oncology, neurology, pulmonology, interventional radiology, oculoplastics depending on etiology.

Surgery

  • Ptosis repair for cosmesis or visual impairment after 12 months (oculoplastic surgery).

ONGOING CARE

Prognosis

  • Postganglionic lesions usually benign.
  • Central/preganglionic lesions have worse prognosis.

Complications

  • Chronic pupillary constriction
  • Cosmetic concerns from ptosis and anisocoria.

REFERENCES

  1. Chen Y, Morgan ML, Palau AEB, et al. Evaluation and neuroimaging of the Horner syndrome. Can J Ophthalmol. 2015;50(2):107-111.
  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. Sadaka A, Schockman SL, Golnik KC. Evaluation of Horner syndrome in the MRI era. J Neuroophthalmol. 2017;37(3):268-272.
  6. Slonim CB, Foster S, Jaros M, et al. Association of oxymetazoline hydrochloride, 0.1%, solution administration with visual field in acquired ptosis: a pooled analysis of 2 randomized clinical trials. JAMA Ophthalmol. 2020;138(11):1168-1175.

Clinical Pearls

  • Triad: ipsilateral miosis, ptosis (<2 mm), anhidrosis.
  • Anisocoria is more pronounced in dim light.
  • Acute Horner syndrome with ipsilateral head/neck pain = carotid artery dissection until proven otherwise.
  • Apraclonidine test preferred over cocaine drops for diagnosis.
  • Oxymetazoline 0.1% eye drops can transiently improve mild ptosis.