Educational draft · awaiting clinical reviewThe full textbook explains uncertainty but does not replace live national or local guidance, specialist advice, or current prescribing information.
Recognise sympathetic pathway failure from the pupil and eyelid findings, distinguish it from physiological anisocoria and rapidly investigate painful or acute Horner syndrome for vascular, central, apical and neck causes.
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.
Brainstem stroke, demyelination, tumour or cervical cord injury can interrupt first-order fibres and usually adds other cranial, cerebellar or long-tract signs.
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.
Internal carotid dissection, cavernous-sinus disease and skull-base lesions damage fibres travelling beside the artery, often with pain or other cranial neuropathies.
Developmental lesions and birth trauma can cause longstanding Horner syndrome, sometimes with iris heterochromia, but this sign is neither required nor uniquely diagnostic.
A lesion affects the three-neuron route from hypothalamus through brainstem, cord, sympathetic chain and carotid plexus to the eye.
Reduced iris dilator activity makes the affected pupil smaller and produces dilation lag, so anisocoria is most apparent in darkness.
Denervation of the superior tarsal muscle causes mild upper-lid ptosis and can elevate the lower lid without extraocular weakness.
Anhidrosis depends on lesion level because sweating fibres separate along external and internal carotid routes after postganglionic fibres diverge.
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.
Longstanding equal asymmetry in bright and dim light with normal eyelids and old photographs supporting stability favours a benign normal variant.
A larger poorly reactive pupil with marked ptosis and impaired eye movements suggests oculomotor palsy rather than Horner syndrome.
A tonic near response, sectoral iris movement or relevant drop and patch exposure supports parasympathetic denervation or drug effect.
Age-related lid change, swelling or previous surgery can lower the eyelid without miosis or dilation lag, separating it from sympathetic failure.
A painful acute Horner syndrome may precede retinal or hemispheric embolism, so delayed arterial imaging risks preventable stroke.
Failure to investigate a preganglionic syndrome can delay diagnosis of apical lung, neck or skull-base cancer with local and metastatic consequences.
Treating the pupil finding in isolation can overlook posterior-circulation stroke, demyelination or compressive myelopathy indicated by accompanying neurological signs.
Congenital ptosis severe enough to obstruct the visual axis can impair visual development, requiring paediatric ophthalmic assessment.
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.
Sympathetic loss weakens Müller's muscle rather than the main levator. Marked complete ptosis with ophthalmoplegia suggests third-nerve, junctional or mechanical disease instead.
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.
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.
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.
Apraclonidine can support the diagnosis, yet a newly painful syndrome needs vascular assessment even if drops are unavailable, equivocal or apparently negative early.
Assuming the larger pupil is always abnormal without comparing bright and dark conditions.
Waiting for pharmacological confirmation before imaging a painful acute Horner syndrome.
Using absence of anhidrosis to rule out postganglionic sympathetic dysfunction.
Calling marked ptosis with restricted eye movements Horner syndrome without considering third-nerve disease.
Completing only brain imaging when arm pain or hand weakness points to the lung apex or lower plexus.
Reassuring from a normal chest radiograph despite a convincing progressive preganglionic syndrome.
Attributing new pain to cluster headache before excluding carotid dissection and structural pathology.
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A 38-year-old develops sudden right-sided neck and orbital pain. Examination shows a smaller right pupil, greater anisocoria in darkness and mild right ptosis without ophthalmoplegia. What is the priority diagnosis to exclude?
National guidance is shown before implementation-dependent detail. Apply principles in context and verify current guidance when a decision affects care. Source check completed 27 Aug 2026; clinical approval remains outstanding.
Editorial contact: Doctor’s Passport editorial team. Source-check date is separate from clinical approval. Report a content problem · Content changes
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.
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.