01OverviewDefinition, clinical context and the essential points that orientate the chapter.
The first-order sympathetic neuron descends from the hypothalamus through the lateral brainstem to the ciliospinal centre in the lower cervical and upper thoracic cord. The second-order neuron exits, passes near the lung apex and ascends the sympathetic chain to the superior cervical ganglion. The third-order neuron travels with the internal carotid artery and through the cavernous sinus to the dilator pupillae and eyelid smooth muscle. This long route explains why one subtle eye sign can mark stroke, cord disease, malignancy, trauma or carotid dissection.
Examination distinguishes impaired dilation from impaired constriction. In Horner syndrome, the abnormal pupil is smaller and anisocoria increases in darkness; light reactions remain present. Physiological anisocoria is usually similar across lighting conditions, stable over time and unaccompanied by ptosis or neurological symptoms. A small irregular pupil from ocular inflammation, previous surgery or medication requires an eye examination rather than automatic neurovascular imaging.
Localisation uses accompanying signs but remains imperfect. Face-and-body sensory findings or cerebellar signs suggest central brainstem disease; arm pain, hand weakness or apical chest symptoms suggest a preganglionic lesion; isolated painful Horner strongly raises postganglionic carotid pathology. Sweat distribution is difficult to test reliably at the bedside, and pharmacological localisation is less urgent than imaging a dangerous syndrome.
History must establish onset from photographs or witnesses, not merely when someone first noticed unequal pupils. Ask about neck manipulation or trauma, headache, transient visual or cerebral symptoms, cough, weight loss, shoulder pain, cancer, neck or chest procedures and cluster-type headaches. Confirmed benign pharmacological testing does not explain a newly painful syndrome unless the full history and imaging decision have been addressed.
Key points
- Horner syndrome reflects interruption of the three-neuron sympathetic pathway from hypothalamus through brainstem and cervical cord, over the lung apex and up the neck with the carotid arteries to the eye.
- The core signs are ipsilateral miosis and mild ptosis, often with apparent elevation of the lower lid; anisocoria is usually more obvious in darkness because the affected pupil dilates slowly.
- Anhidrosis varies with lesion level because facial sweating fibres separate along external and internal carotid routes; its absence does not exclude the syndrome.
- Measure pupils in bright and dim light after allowing dilation, record eyelid position and look for dilation lag. Compare old photographs because lifelong physiological anisocoria is common.
- Painful acute Horner syndrome—especially unilateral neck, facial or orbital pain—requires urgent arterial imaging for carotid dissection even if limb examination is initially normal.
- Brainstem or first-order lesions may add vertigo, nystagmus, dysphagia, ataxia, crossed sensory loss or long-tract signs and should enter an emergency posterior-circulation pathway.
- Preganglionic lesions can arise at the lung apex, thoracic inlet or cervical sympathetic chain and may accompany shoulder or arm pain, hand weakness, neck mass, surgery or trauma.
- Postganglionic lesions follow the internal carotid into the cavernous sinus and orbit and can accompany trigeminal pain, ocular motor palsies or headache syndromes.
- Pharmacological pupil testing can confirm sympathetic denervation in appropriate specialist settings but should not delay emergency vascular or structural imaging when onset or pain is concerning.
- Congenital Horner syndrome may include heterochromia, but heterochromia is neither required nor a reliable discriminator in acquired adult presentations.
- Do not confuse Horner syndrome with a third-nerve palsy: Horner produces a small pupil and mild ptosis without extraocular weakness, whereas third-nerve disease often impairs eye movements and may enlarge the pupil.
- When duration is genuinely longstanding and no red flags exist, imaging strategy remains specialist-led because the whole sympathetic pathway may require assessment and incidental testing can be extensive.
02AetiologyUnderlying causes, associations and risk factors, with why each one matters.
Central sympathetic pathway disease
Brainstem stroke, demyelination, tumour or cervical cord injury can interrupt first-order fibres and usually adds other cranial, cerebellar or long-tract signs.
Preganglionic chest or neck disease
Apical lung tumour, thoracic-inlet mass, trauma and neck or chest surgery can injure the second-order pathway before it reaches the superior cervical ganglion.
Postganglionic carotid and skull-base disease
Internal carotid dissection, cavernous-sinus disease and skull-base lesions damage fibres travelling beside the artery, often with pain or other cranial neuropathies.
Congenital or birth injury
Developmental lesions and birth trauma can cause longstanding Horner syndrome, sometimes with iris heterochromia, but this sign is neither required nor uniquely diagnostic.
03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.
- 1Sympathetic pathway interruption
A lesion affects the three-neuron route from hypothalamus through brainstem, cord, sympathetic chain and carotid plexus to the eye.
- 2Loss of pupillary dilation
Reduced iris dilator activity makes the affected pupil smaller and produces dilation lag, so anisocoria is most apparent in darkness.
- 3Loss of eyelid tone
Denervation of the superior tarsal muscle causes mild upper-lid ptosis and can elevate the lower lid without extraocular weakness.
- 4Variable sudomotor loss
Anhidrosis depends on lesion level because sweating fibres separate along external and internal carotid routes after postganglionic fibres diverge.
04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.
New partial Horner syndrome with ipsilateral neck, face or orbital pain, headache or transient retinal or cerebral symptoms strongly suggests carotid dissection and requires emergency head-and-neck vascular imaging.
Horner syndrome with vertigo, nystagmus, ipsilateral facial sensory loss, contralateral body pain-temperature loss, dysphagia or limb ataxia supports a first-order lesion such as lateral medullary stroke.
Horner syndrome plus persistent shoulder or medial arm pain, hand weakness or wasting, cough, constitutional symptoms or an apical chest finding suggests lower brachial-plexus and sympathetic-chain involvement from a thoracic-inlet lesion.
Miosis and ptosis accompanied by ocular motor palsies or trigeminal V1 or V2 sensory change points to the cavernous sinus or orbital apex and raises vascular, inflammatory, infectious and neoplastic causes.
Neck, chest, spinal or carotid procedures and penetrating or traction injury can interrupt the pathway. Timing and accompanying vascular or plexus injury determine whether postoperative observation or urgent imaging is appropriate.
Small stable pupil asymmetry present in old photographs, similar in bright and dim conditions and unaccompanied by ptosis or neurological symptoms supports a benign variant after competent assessment.
Transient partial Horner signs can accompany strictly unilateral orbital pain with autonomic features, but a first or atypical painful episode still requires exclusion of carotid and structural disease.
05InvestigationsWhat to request, why it matters and how to interpret it.
Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.
- 01
Pupil measurements in bright and dim illuminationFirst step - Why
- Determine which pupil is abnormal and whether anisocoria increases when sympathetic dilation is required.
- Interpretation and limitations
- Greater asymmetry in darkness with delayed dilation supports Horner syndrome. Allow adequate dark adaptation and document millimetres rather than 'unequal'; ocular drugs and prior surgery can confound.
- 02
Apraclonidine pharmacological testing - Why
- Support sympathetic denervation by demonstrating supersensitivity in an appropriate specialist-led non-emergency setting.
- Interpretation and limitations
- Reversal of anisocoria can support Horner syndrome, but denervation supersensitivity may be incomplete very early. Test risks, age restrictions and interpretation require ophthalmic or neuro-ophthalmic protocol.
- 03
CT angiography or MR angiography of head and neck - Why
- Detect carotid or vertebral dissection, aneurysm and acute cerebrovascular disease in painful or sudden presentations.
- Interpretation and limitations
- Coverage must include the relevant arterial pathway and skull base. A negative study does not end evaluation when technical quality or progressive focal signs remain concerning; discuss with neuroradiology.
- 04
MRI brain and cervical cord - Why
- Assess first-order lesions from brainstem infarction, demyelination, tumour, syrinx or cord disease.
- Interpretation and limitations
- Select urgent diffusion and vascular sequences for acute brainstem syndromes and tailored cord imaging for myelopathic signs. Horner syndrome alone does not determine one protocol.
- 05
CT chest and neck-pathway imaging - Why
- Evaluate lung apex, mediastinum, thyroid, neck masses and brachial-plexus region in a suspected preganglionic lesion.
- Interpretation and limitations
- Persistent shoulder-arm pain, weakness, smoking history, cough or weight loss changes urgency and cancer referral. A plain chest radiograph can miss an apical lesion and may not complete assessment.
- 06
Old photographs and procedural records - Why
- Establish chronicity and identify prior surgery, trauma or device placement along the sympathetic chain.
- Interpretation and limitations
- Images with both eyes under similar lighting are most useful. Longstanding asymmetry lowers some acute probabilities but does not explain new pain or other neurological findings.
06Differential diagnosisRealistic alternatives and the features that help distinguish them.
Physiological anisocoria
Longstanding equal asymmetry in bright and dim light with normal eyelids and old photographs supporting stability favours a benign normal variant.
Third-nerve palsy
A larger poorly reactive pupil with marked ptosis and impaired eye movements suggests oculomotor palsy rather than Horner syndrome.
Adie or pharmacological pupil
A tonic near response, sectoral iris movement or relevant drop and patch exposure supports parasympathetic denervation or drug effect.
Mechanical ptosis
Age-related lid change, swelling or previous surgery can lower the eyelid without miosis or dilation lag, separating it from sympathetic failure.
07ManagementImmediate care, first-line treatment, alternatives and escalation.
01Painful acute HornerImage the cervical arteries nowFirst stepNew miosis and mild ptosis accompanies ipsilateral neck, facial, orbital or head pain, with or without transient neurological symptoms.+
- 1EscalationEstablish last known well and trauma or manipulation history, perform ABCDE and a complete stroke and cranial examination and compare pupils in bright and dim light without delaying escalation.
- 2PreferredContact the stroke or neurovascular service and obtain urgent head-and-neck CTA or the locally preferred arterial imaging for carotid dissection and associated infarction.
- 3Use antithrombotic and follow-up treatment only under the responsible stroke team after haemorrhage and vascular anatomy are defined, and safety-net recurrent retinal or cerebral symptoms.
02Central neurological HornerSearch brainstem and cordPupil and eyelid signs occur with ataxia, crossed sensation, dysphagia, long-tract deficit, cord signs or acute severe vertigo.+
- 1Map cranial nerves, eye movements, bulbar function, limbs, sensation and coordination and activate the emergency posterior-circulation or spinal pathway according to tempo and level.
- 2Arrange CT vascular imaging and MRI brain or cord through neurology, stroke and neuroradiology, recognising that early posterior-fossa CT can be unrevealing.
- 3Monitor swallowing, respiratory function and neurological progression and treat the defined vascular, inflammatory, compressive or neoplastic cause with the specialist service.
03Subacute isolated syndromeInvestigate the sympathetic routeHorner signs are persistent without acute pain or focal instability, and physiological anisocoria is not established.+
- 1Confirm the phenotype with standard lighting, photographs and specialist pharmacological testing where appropriate and review chest, neck, cancer, trauma and procedural history.
- 2Use age, duration and accompanying symptoms to plan imaging of brain, neck, chest and carotid pathway with neuro-ophthalmology and radiology rather than ordering fragmented low-yield tests.
- 3EscalationCommunicate negative and incidental results, arrange surveillance when cause remains uncertain and escalate any new pain, weakness, dysphagia, cough, weight loss or visual symptoms.
08ComplicationsImportant consequences, why they occur and why they matter clinically.
Ischaemic stroke from dissection
A painful acute Horner syndrome may precede retinal or hemispheric embolism, so delayed arterial imaging risks preventable stroke.
Progression of underlying malignancy
Failure to investigate a preganglionic syndrome can delay diagnosis of apical lung, neck or skull-base cancer with local and metastatic consequences.
Missed brainstem or cord disease
Treating the pupil finding in isolation can overlook posterior-circulation stroke, demyelination or compressive myelopathy indicated by accompanying neurological signs.
Amblyopia in congenital disease
Congenital ptosis severe enough to obstruct the visual axis can impair visual development, requiring paediatric ophthalmic assessment.
09Monitoring and follow-upTreatment response, safety checks and longer-term review.
- Repeat pupil size in matched bright and dim lighting and track ptosis and new ocular-motor or trigeminal findings during an evolving presentation.
- In suspected dissection, monitor for transient monocular loss, aphasia, weakness, sensory change and headache progression while urgent imaging and stroke review proceed.
- Record neck, chest, shoulder and arm symptoms and examine hand power and bulk during follow-up of a possible preganglionic lesion.
- Review every imaging field for whether the complete suspected pathway was covered; a negative brain scan alone does not assess lung apex or cervical carotid.
- Document pharmacological test agent, concentration, timing and pupil measurements when performed, because informal descriptions are difficult to reinterpret.
- Give an emergency safety net for new pain, focal deficit, severe vertigo, dysphagia, visual loss or reduced consciousness.
10Special situationsVariants, exceptions and circumstances that change the usual approach.
Anisocoria changes with light
When inequality is greater in the dark, the smaller pupil is failing to dilate; when greater in bright light, the larger pupil is failing to constrict. This directs the autonomic pathway.
Ptosis is usually subtle
Sympathetic loss weakens Müller's muscle rather than the main levator. Marked complete ptosis with ophthalmoplegia suggests third-nerve, junctional or mechanical disease instead.
Pain localises risk
The sympathetic fibres run with the internal carotid after the superior cervical ganglion. New ipsilateral neck or orbital pain plus Horner signs is therefore a dissection warning.
Sweating is variable
Some facial sudomotor fibres travel with the external carotid while ocular fibres follow the internal carotid. Postganglionic Horner syndrome may have little clinically detectable anhidrosis.
Old photographs add timing
A passport or family image may show longstanding anisocoria or ptosis, but differences in flash and gaze can mislead. Use several comparable images and current symptoms.
Pharmacology does not replace imaging
Apraclonidine can support the diagnosis, yet a newly painful syndrome needs vascular assessment even if drops are unavailable, equivocal or apparently negative early.
11Common pitfallsFrequent interpretation and management errors.
- 01
Assuming the larger pupil is always abnormal without comparing bright and dark conditions.
- 02
Waiting for pharmacological confirmation before imaging a painful acute Horner syndrome.
- 03
Using absence of anhidrosis to rule out postganglionic sympathetic dysfunction.
- 04
Calling marked ptosis with restricted eye movements Horner syndrome without considering third-nerve disease.
- 05
Completing only brain imaging when arm pain or hand weakness points to the lung apex or lower plexus.
- 06
Reassuring from a normal chest radiograph despite a convincing progressive preganglionic syndrome.
- 07
Attributing new pain to cluster headache before excluding carotid dissection and structural pathology.