Horner syndrome is a syndrome that presents with various ocular and systemic findings due to disruption of the ocular sympathetic pathway. The three main signs are miosis, ptosis, and anhidrosis, and the lesion can occur at central, preganglionic, or postganglionic sites.
The condition is named after Claude Bernard (1852) and Johann Friedrich Horner (1869). It is also called Bernard-Horner syndrome. The ocular sympathetic pathway is a long route from the hypothalamus through three neurons to the pupillary dilator muscle, and the causative disease and urgency vary greatly depending on the lesion site.
Miosis is moderate, and anisocoria is most noticeable in dim light. The pupillary light reflex remains normal, which is an important distinguishing feature from Adie pupil and oculomotor nerve palsy. Denervation of Müller’s muscle in the upper eyelid causes mild ptosis of about 2 mm, and involvement of Müller’s muscle in the lower eyelid causes mild elevation (upside-down ptosis). Together, these result in narrowing of the palpebral fissure and apparent enophthalmos.
It is usually mild, about 2 mm, due to sympathetic denervation of Müller’s muscle in the upper eyelid. The lower eyelid also elevates slightly (upside-down ptosis), causing apparent narrowing of the palpebral fissure and enophthalmos. It is important to distinguish from complete ptosis (oculomotor nerve palsy).
| Lesion Site | Area of Anhidrosis |
|---|---|
| Central (first-order neuron) | Whole half of the body |
| Preganglionic (second-order neuron) | Half of the face |
| Postganglionic (third-order neuron) | Medial forehead and tip of the nose (may be normal) |
If congenital or onset within the first year of life, it is accompanied by iris hypopigmentation (heterochromia). Causes include birth trauma such as forceps delivery, but many cases are idiopathic.
The oculosympathetic pathway consists of a three-neuron chain, and the causative disease differs depending on the site of the lesion.
Central (first-order neuron)
Pathway: Hypothalamus to Budge center (C8-T2)
Common causes: Brainstem infarction (Wallenberg syndrome), brainstem tumor, multiple sclerosis
Associated findings: Hypothalamic lesion → contralateral hemiparesis and sensory loss; pontine lesion → abducens nerve palsy; medullary lesion → Wallenberg syndrome (ipsilateral facial sensory loss, contralateral loss of pain and temperature sensation, lateropulsion, skew deviation)
Preganglionic (second-order neuron)
Pathway: Budge center to stellate ganglion (superior cervical ganglion)
Common causes: Pancoast tumor (apical lung tumor), brachial plexus palsy, subclavian artery aneurysm, post-neck surgery
Features: Because the pathway passes through the lung apex and mediastinum, lung cancer and mediastinal tumors should be ruled out first
Postganglionic (third-order neuron)
Pathway: Stellate ganglion to pupillary dilator muscle
Common causes: Internal carotid artery dissection, post-thyroid surgery, post-carotid endarterectomy, traumatic internal carotid artery dissection
Features: Acute onset with neck pain or headache strongly suggests dissection, which is an emergency
GCA is a granulomatous vasculitis of medium and large vessels that occurs in individuals aged 50 years or older, and it has been reported to be associated with Horner syndrome 1). In an analysis of a case series of GCA patients, Horner syndrome was observed in 2 out of 53 cases (approximately 4%) 1).
In a case report, a 67-year-old man presented with right trochlear nerve palsy and left Horner syndrome, with elevated ESR of 70 mm/hr and CRP of 10 mg/L. After starting prednisone 60 mg, diplopia resolved, but Horner syndrome persisted 1). Another 71-year-old man presented with bilateral headache, jaw pain, left Horner syndrome, and skew deviation, with ESR of 68 mm/hr and CRP of 46 mg/L. All symptoms including Horner syndrome resolved 3 days after starting prednisone 60 mg 1). In both cases, temporal artery biopsy confirmed GCA, and MRI/MRA showed no abnormalities 1).
Instill 1% apraclonidine hydrochloride (Iopidine®) into both eyes (off-label use).
Use 5% cocaine instillation to inhibit norepinephrine reuptake and assess mydriasis. In normal eyes, mydriasis (++) occurs after 90–120 minutes, but in Horner eyes, mydriasis is poor.
| Eye drops | Evaluation time | Normal | Central | Preganglionic | Postganglionic |
|---|---|---|---|---|---|
| 5% cocaine | 90–120 min | ++ | + | − | − |
| 5% tyramine | 45 min | + | + | + | − |
| 1.25% adrenaline | 60 minutes | − | − | + | ++ |
Tyramine causes the release of norepinephrine from nerve terminals. In preganglionic lesions, norepinephrine remains in the nerve terminals, resulting in mydriasis. In postganglionic lesions, it does not remain, so no mydriasis occurs.
Hydroxyamphetamine (1%) eye drops can also differentiate between preganglionic and postganglionic lesions: preganglionic lesions show mydriasis (+), while postganglionic lesions show no mydriasis (−)2).
Since denervation supersensitivity is not fully acquired until at least 3 days after onset, false negatives may occur in the acute phase (within 3 days of onset). The cocaine eye drop test is recommended in the acute phase, but cocaine eye drops may be difficult to obtain in Japan.
Perform imaging tests according to the lesion site. Imaging tests corresponding to each lesion site are required, but chest imaging is prioritized to rule out lung cancer and mediastinal tumors.
For new cases aged 50 years or older, measure ESR and CRP 1). In suspected GCA, perform temporal artery biopsy 1).
Treatment of the underlying disease is the highest priority. If no other systemic findings are present and it is judged to be benign, observation is appropriate.
If the underlying disease is treated, the prognosis for recovery varies depending on the site and cause of the lesion. Iatrogenic (post-surgical) and idiopathic cases often have a benign course. In carotid artery dissection, symptoms may improve with emergency treatment. Neoplastic causes depend on the prognosis of the tumor itself. In GCA cases, there are reports of symptom improvement with prednisone, but Horner syndrome may persist in some cases.
Because this pathway is long, various causes from the brainstem to the lung apex and neck can be involved.
The superior tarsal muscle (Müller’s muscle) of the upper eyelid (contributing about 2 mm of eyelid elevation) and the inferior tarsal muscle of the lower eyelid receive sympathetic innervation. Denervation causes ptosis (about 2 mm) and elevation of the lower eyelid (upside-down ptosis), leading to narrowing of the palpebral fissure and apparent enophthalmos.
In postganglionic lesions, the release of norepinephrine from nerve endings is interrupted. This leads to compensatory up-regulation of α1 receptors on the dilator pupillae muscle. Even a small α1 effect (such as the α1 action of apraclonidine) can cause mydriasis, which is the basis for pharmacological diagnosis. It takes at least 3 days to develop this supersensitivity.
It is presumed that vasculitis in GCA extends to the perforating branches of the vertebral artery, reducing blood flow to the brainstem and causing first-order neuron damage 1). Alternatively, granulomatous inflammation in the wall of the internal carotid artery may directly damage the sympathetic plexus, causing postganglionic damage 1). Literature reviews report both central and postganglionic involvement, and the site of damage varies by case 1).
Reports of Horner syndrome associated with GCA are rare, with fewer than 10 cases in the literature, and the detailed pathogenesis remains unclear 1). In 8 previously reported cases, systemic symptoms improved in all patients with prednisone 60 mg/day (approximately 1 mg/kg/day). Recovery from Horner syndrome varied among cases, with some showing complete resolution 3 days after treatment initiation and others having residual symptoms 1). Central lesions (first-order neuron) are likely due to brainstem ischemia and are often accompanied by trochlear nerve palsy or skew deviation 1). Many cases show no abnormalities on MRI/MRA, and diagnosis based on clinical findings and inflammatory markers is considered important 1).
Sverdlichenko I, Lam C, Donaldson L, Margolin E. Horner Syndrome in Giant Cell Arteritis: Case Series and Review of the Literature. J Neuroophthalmol.
Martin TJ. Horner syndrome: a clinical review. ACS Chem Neurosci. 2018;9:177-186.
