Pourfour du Petit syndrome

Key Points at a Glance

Highlights of This Disease

• Pourfour du Petit syndrome (PDPS) is a rare syndrome caused by overactivity of the ocular sympathetic pathway.
• It is characterized by the triad of ipsilateral mydriasis, eyelid retraction, and hyperhidrosis, presenting a clinical picture opposite to Horner syndrome.
• Most cases are traumatic or iatrogenic in origin, with diverse causes including vascular, neoplastic, and infectious etiologies.
• Diagnosis is primarily clinical, and neuroimaging along the ocular sympathetic axis is important to exclude structural lesions.
• Treatment is mainly directed at the underlying condition, and specific treatment for PDPS itself is often unnecessary.
• For persistent symptoms, oral clonidine or sympathectomy may be options, and spontaneous resolution can occur in some cases.

1. What is Pourfour du Petit Syndrome?

Pourfour du Petit Syndrome (PDPS) is a rare syndrome caused by overactivity (excessive stimulation) of the ocular sympathetic pathway.

In 1727, French anatomist and ophthalmologist François Pourfour du Petit first reported mydriasis, eyelid retraction, and hemifacial hyperhidrosis in a soldier with a neck injury ¹⁾.

The classic triad is as follows:

• Mydriasis: ipsilateral pupillary dilation
• Eyelid retraction: widening of the palpebral fissure due to sympathetic overactivity of the superior tarsal muscle (Müller’s muscle)
• Hyperhidrosis: Increased sweating on the same side of the face

PDPS is caused by a lesion in the same ocular sympathetic pathway as Horner syndrome. The underlying mechanism is common: when the pathway is “stimulated or overactive,” PDPS develops; when it is “blocked,” Horner syndrome occurs ¹⁾. The two syndromes present clinically opposite features functionally.

This is a very rare syndrome, and no specific epidemiological incidence rates have been reported. The duration of symptoms ranges from at least one month to indefinite, and some cases resolve spontaneously.

Q How is Pourfour du Petit syndrome different from Horner syndrome?

A

Horner syndrome presents with miosis, ptosis, and anhidrosis due to “blockage” of the ocular sympathetic pathway, while PDPS presents with mydriasis, lid retraction, and hyperhidrosis due to “stimulation or overactivity” of the same pathway. The underlying pathophysiology (lesion in the ocular sympathetic chain) is common, but the clinical findings are opposite. See “Pathophysiology and Detailed Mechanism” section for details.

2. Main Symptoms and Clinical Findings

Subjective Symptoms

• Blurred vision: May experience blurred vision¹⁾
• Photophobia: Light sensitivity due to incomplete iris shading from mydriasis¹⁾
• Increased sweating: Hyperhidrosis on the affected side of the face
• Course of symptoms: Transient episodes triggered by Valsalva maneuver (straining) may precede progression to persistent symptoms¹⁾

Clinical Findings (Findings Confirmed by Physician Examination)

The associated findings differ depending on the level of the affected neuron (first to third order neurons).

Key Findings

• Mydriasis: Ipsilateral pupillary dilation¹⁾
• Eyelid retraction: Widening of the palpebral fissure due to overactivity of the superior tarsal muscle¹⁾
• Exophthalmos: May be accompanied by mild proptosis¹⁾
• Hemifacial hyperhidrosis: Increased sweating on the ipsilateral face (not present in third-order neuron lesions)¹⁾

Comparison with Horner syndrome

PDPS

Mydriasis: ipsilateral pupillary dilation

Lid retraction: widened palpebral fissure and upper eyelid retraction

Hyperhidrosis: increased sweating on the ipsilateral face and forehead (absent in third-order neuron lesions)

Horner syndrome

Miosis: Constriction of the pupil on the same side

Ptosis: Narrowing of the palpebral fissure and drooping of the upper eyelid

Anhidrosis: Decreased sweating on the same side of the face and forehead

Additional findings by lesion level

• First-order neuron lesion: May be accompanied by ipsilateral hemihyperhidrosis and signs of central nervous system dysfunction (contralateral hemiparesis, sensory loss, vertical gaze palsy, ataxia, cranial nerve palsy, dizziness, dysphagia, nystagmus, facial weakness)¹⁾
• Second-order neuron lesion: May be accompanied by mydriasis, proptosis, lid retraction, facial hyperhidrosis, as well as arm/neck pain, brachial plexus palsy, vocal cord paralysis, and phrenic nerve palsy¹⁾
• Third-order neuron damage: Presents with mydriasis, proptosis, and lid retraction, but without hyperhidrosis. This is because the sudomotor fibers branch along the external carotid artery and are not included in the postganglionic fibers that travel via the internal carotid artery¹⁾.

Q Do symptoms differ depending on the site of nerve damage?

A

Yes, they differ. In first- and second-order neuron damage, the triad of mydriasis, lid retraction, and hyperhidrosis is present, but in third-order (postganglionic) neuron damage, hyperhidrosis is absent. This is because the sudomotor fibers branch from the superior cervical ganglion along the external carotid artery and are not included in the postganglionic fibers that travel along the internal carotid artery¹⁾.

3. Causes and Risk Factors

PDPS results from a lesion in the same ocular sympathetic pathway as Horner syndrome, but the mechanism is “stimulation/hyperactivity” rather than “blockage” of the pathway¹⁾.

Traumatic/Iatrogenic

• Cervical trauma/blunt trauma: Long known as a cause of PDPS
• After local anesthesia: Oral anesthesia, epidural anesthesia, brachial plexus block, interscalene block, etc.¹⁾
• Vascular catheter insertion/removal, carotid artery-related surgery¹⁾

Vascular

• Carotid artery dissection
• Thoracic aortic aneurysm
• Internal jugular vein dilation: Compensatory dilation due to contralateral internal jugular vein agenesis has been reported to compress the second-order neuron ¹⁾

Neoplastic

• Thyroid cancer (compression of internal carotid artery), esophageal cancer (pleural extension), apical lung tumor, paravertebral metastasis, neurofibroma, thyroid adenoma ¹⁾

Infectious

• Tuberculosis, aspergillosis, cryptococcosis (reported as a cause of second-order neuron PDPS) ¹⁾

Central

• Bilateral thalamic and midbrain infarction (basilar artery tip stroke), acute epidural hematoma in the spinal subdural space

Others

• Cervical spine malformation, migraine and cluster headache¹⁾

When to see a doctor

If you notice symptoms such as asymmetry in eye size (eyelid retraction), unequal pupil size, or increased sweating on one side of the face, please consult an ophthalmologist or neurologist. If symptoms occur after trauma, surgery, or local anesthesia, it is important to inform your doctor.

4. Diagnosis and examination methods

PDPS is primarily a clinical diagnosis. It is diagnosed based on the triad of mydriasis, eyelid retraction, and hyperhidrosis, along with medical history (trauma, surgery, local anesthesia). Neuroimaging along the ocular sympathetic pathway is recommended to exclude structural lesions.

Imaging

Select imaging based on the suspected level of the lesion.

Lesion level	Recommended imaging	Lesions to exclude
First-order neuron	Head MRI / non-contrast head CT	Stroke, hemorrhage, intracranial tumor
Second-order neuron	Chest/neck CT/MR angiography	Apical lung mass, thoracic aortic aneurysm, infection
Third-order neuron	Head and neck MR angiography	Internal carotid artery dissection, aneurysm, thrombosis

In the acute phase, head and neck CT + CT angiography (CTA) is performed to rule out carotid artery dissection and tumors. Head and neck MRI combined with MRA is useful for excluding structural lesions along the sympathetic chain ¹⁾.

Differential diagnosis

• Horner syndrome: Classic triad (miosis, ptosis, anhidrosis). Apraclonidine (0.5–1%) eye drops cause dilation of the affected pupil and constriction of the healthy eye (reversal of anisocoria). Sensitivity 88–100%.
• Mydriasis associated with oculomotor nerve palsy: Accompanied by eye movement disorders (ptosis, downward and outward deviation)
• Tonic pupil (Adie pupil): Unilateral mydriasis, loss of light reflex, slow constriction to near response. Differentiated by hypersensitivity to low-concentration pilocarpine (0.1–0.125%)
• Benign episodic mydriasis: Transient unilateral mydriasis, more common in young women. May be associated with headache. Thought to be transient sympathetic hyperactivity, distinct from PDPS
• Pharmacologic mydriasis: Mydriasis due to anticholinergic drugs such as atropine. No response to high-concentration pilocarpine (1–2%)
• Traumatic mydriasis: Due to iris sphincter tear, etc.

5. Standard Treatment

Treatment of the underlying disease is the highest priority. Many patients do not require specific treatment for PDPS itself.

Pharmacotherapy

• Clonidine: α2-adrenergic receptor agonist. Reported to be effective for symptom relief.

Surgical treatment

• Sympathectomy: Used to suppress sympathetic nerve activity in persistent PDPS. Reported to be effective in up to 90% of cases. Also indicated for reducing hyperhidrosis and conjunctivitis/keratitis associated with proptosis ¹⁾

Follow-up observation

• When surgery is not indicated or the patient refuses: regular neurological, ophthalmological, and vascular follow-up is recommended ¹⁾

Precautions in treatment

Symptoms of PDPS may resolve spontaneously, but if an underlying disease (such as tumor, carotid artery dissection, or aortic aneurysm) is hidden, urgent intervention is required. Regardless of the severity of symptoms, priority should be given to investigating the cause first.

Q Can Pourfour du Petit syndrome resolve on its own?

A

Yes, some cases resolve spontaneously. The duration of symptoms ranges from a minimum of one month to indefinite, and the prognosis depends on the nature of the underlying disease. Treatment of the underlying disease often leads to symptom improvement; for persistent cases, clonidine or sympathectomy are options.

6. Pathophysiology and detailed mechanism

Ocular sympathetic 3-neuron pathway

The ocular sympathetic pathway consists of three neurons.

• First-order neuron (central): Originates from the posterolateral hypothalamus, descends through the midbrain and medulla oblongata to reach the spinal cord at C8-T2 (Budge’s ciliospinal center), where it synapses with the second-order neuron.
• Second-order neuron (preganglionic): Exits the spinal cord with the first thoracic nerve root, passes under the subclavian artery and over the lung apex, ascends in the paravertebral sympathetic chain, and synapses at the superior cervical ganglion at the level of the second cervical vertebra¹⁾.
• Third-order neuron (postganglionic): Branches from the superior cervical ganglion.
  • Branch along the external carotid artery: Controls facial sweating and vasomotor functions.
  • Branches along the internal carotid artery: further branch to innervate the vasomotor functions of the forehead and eyelids, lacrimal gland, superior tarsal muscle (Müller’s muscle), and iris dilator muscle¹⁾

Mechanism of PDPS Onset

When a “stimulus” occurs at any point in this three-neuron pathway, sympathetic hyperactivity results, leading to PDPS. When the pathway is “blocked,” Horner syndrome develops. Both syndromes share the same pathophysiology (damage to the ocular sympathetic chain) but present clinically opposite functional features¹⁾.

The reason why third-order neuron lesions are not accompanied by hyperhidrosis is that sudomotor fibers branch from the superior cervical ganglion along the external carotid artery and are not included in the postganglionic fibers via the internal carotid artery¹⁾.

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7. Latest Research and Future Perspectives (Research-stage Reports)

For patients: Please read this

The following content is currently at the research stage or under clinical trial and is not standard treatment available at general hospitals. It is reference information for experts regarding future medical developments.

Report of a novel pathogenesis due to internal jugular vein agenesis

PDPS due to internal jugular vein dilation had rarely been reported, but a new pathogenesis was reported in 2023.

Salazar-Orellana et al. (2023) reported a case of a 64-year-old woman in whom compensatory right internal jugular vein dilation due to left internal jugular vein agenesis compressed the right cervical sympathetic chain, causing second-order neuron PDPS¹⁾. The patient had experienced transient right-sided hyperhidrosis, blurred vision, and photophobia episodes triggered by Valsalva maneuver for 2 years, which became persistent 2 weeks prior. CT/MR angiography confirmed left internal jugular vein agenesis and compression of the sympathetic chain by the dilated right internal jugular vein. The patient declined surgery, and regular neurological, ophthalmological, and vascular follow-up was planned.

Internal jugular vein agenesis is a vascular malformation present in approximately 0.05–0.25% of the general population and is usually asymptomatic. It has been reported that 20% of patients with venous malformations of the neck and face have associated developmental venous anomalies in the brain, and intracranial angiography should be considered when a vascular malformation is identified¹⁾.

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8. References

1. Salazar-Orellana JLI, Aceytuno RD, Vasquez-Cortez NA, et al. Pourfour Du Petit Syndrome Due to Ipsilateral Internal Jugular Vein Distention. Cureus. 2023;15(5):e38741.
2. Evans RW, Garibay A, Foroozan R. Pourfour du Petit Syndrome Associated With Right Eye Pressure. Headache. 2017;57(6):937-942. PMID: 28295246.
3. Nadal J, Daien V, Audemard D, Jeanjean L. Pourfour du Petit Syndrome: A Rare Association With Cluster Headache. Ophthalmic Plast Reconstr Surg. 2019;35(1):e15-e16. PMID: 30614949.