Raeder's syndrome

Key Points at a Glance

Essentials of This Disease

• This is a rare syndrome in which the ipsilateral cervical sympathetic nerve, recurrent laryngeal nerve, and phrenic nerve are affected.
• It is characterized by the triad of Horner syndrome, vocal cord paralysis (hoarseness), and unilateral diaphragmatic paralysis, but diagnosis is possible even in incomplete forms.
• The most common cause is malignant tumors (breast cancer, lung cancer), and prompt investigation of the cause is essential.
• Ocular findings of Horner syndrome (ptosis, miosis, anhidrosis) are subtle and easily overlooked.
• The anatomical basis for this condition is that at the level of the sixth cervical vertebra, the three nerves run adjacent to each other in a narrow area.
• The mainstay of treatment is curative therapy for the underlying disease, and the prognosis depends on the causative condition.

1. What is Rowland Payne Syndrome?

Rowland Payne Syndrome (RPS) is a rare clinical syndrome caused by simultaneous damage to the ipsilateral cervical sympathetic plexus, recurrent laryngeal nerve (a branch of the vagus nerve), and phrenic nerve. It was first described by Dr. Rowland Payne in 1981 in three cases (all with metastatic breast cancer), and subsequent reports have repeatedly confirmed this triad ¹.

Clinically, it is characterized by the following three signs:

• Horner syndrome: ipsilateral ptosis, miosis, and anhidrosis
• Vocal cord paralysis: causing hoarseness and dysphagia
• Unilateral diaphragmatic paralysis: usually asymptomatic and diagnosed on chest X-ray

Even if all three signs are not present, it may be diagnosed as an incomplete form. There are only a few case reports and series in the literature, and it is classified as a rare disease. It is often seen in patients with underlying malignant tumors, but there are also reports due to non-malignant diseases (trauma, infectious lymphadenopathy)².

Q Can Roland-Pain syndrome be diagnosed even if all three signs are not present?

A

It is not necessary for all three signs to be completely present; diagnosis is possible even in incomplete forms. The important thing is to evaluate whether a single lesion simultaneously affects the areas traversed by the cervical sympathetic nerve, recurrent laryngeal nerve, and phrenic nerve.

2. Main Symptoms and Clinical Findings

Subjective Symptoms

• Hoarseness (voice raspiness): Due to recurrent laryngeal nerve (vocal cord) paralysis. It is one of the most easily noticeable symptoms.
• Dysphagia: May occur with vocal cord paralysis.
• Ipsilateral shoulder abnormal sensation/pain: Symptoms due to nerve compression or infiltration.
• Respiratory symptoms: Diaphragmatic paralysis usually causes few subjective symptoms.
• Systemic symptoms: If the underlying disease is a malignant tumor, weight loss and fatigue may occur.

Clinical Findings (Findings Confirmed by Physician Examination)

Horner Syndrome (Main Ophthalmic Finding of RPS)

• Ipsilateral ptosis: Mild drooping due to dysfunction of the Müller muscle (sympathetic innervation).
• Upside-down ptosis: Slight elevation of the lower eyelid.
• Miosis: More noticeable in dim light. In bright environments, anisocoria between the affected and healthy sides is less apparent.
• Anhidrosis: Impaired sweating on the ipsilateral face. May go unnoticed in a temperature-controlled environment.

These ocular findings are subtle and can be easily missed, especially by inexperienced examiners.

Vocal cord paralysis and diaphragmatic paralysis

• Vocal cord paralysis: Movement of the ipsilateral vocal cord is observed on laryngeal fiberscopy.
• Unilateral diaphragmatic paralysis: Seen as elevation of the affected diaphragm on chest X-ray. Patients are usually asymptomatic.

Associated adjacent nerve disorders

• Klumpke paralysis: Occurs when the lower trunk of the brachial plexus (C8–T1) is involved.
• Pancoast syndrome: May occur when the lung apex is involved.

Q Why are the ocular findings of Horner syndrome easily overlooked?

A

Ptosis due to Müller muscle dysfunction is mild. Anhidrosis may go unnoticed in a temperature-controlled environment, and miosis is only noticeable in the dark, so anisocoria is often not obvious during a routine examination in a well-lit room.

3. Causes and Risk Factors

RPS occurs when an underlying disease compresses or infiltrates the nerve pathways in the mediastinum, thoracic inlet, or neck.

Malignant tumors (most common):

• Breast cancer and lung cancer: These are the most frequent causes ¹². In breast cancer, cases have been reported where RPS develops as a late recurrence long after initial treatment ².
• Neuroblastoma and anaplastic thyroid carcinoma: These are relatively rare malignant tumors. In children, cervicomediastinal neuroblastoma has been reported to cause RPS in combination with superior mediastinal syndrome ³. In adults, cases due to anaplastic thyroid carcinoma are also known ⁴.
• Not only a single mass, but also multiple independent lesions can collectively cause RPS.

Non-malignant causes:

• Tuberculous lymphadenitis: Inflammatory granulomas compress the nerve.
• Empyema thoracis: Intrathoracic infection spreads to perineural structures.
• Infectious lymphadenopathy: Extensive inflammation of the lung, pleura, first rib, and soft tissues explains atypical presentations of RPS.

Special cases:

• Presentation mimicking neurodegenerative disease: A case of recurrent breast cancer initially diagnosed as amyotrophic lateral sclerosis (ALS) with upper limb motor paralysis and cachexia has been reported, requiring differentiation from neurodegenerative diseases ².
• Neonatal RPS: Reported immediately after forceps delivery. It is presumed to be due to mechanical shear injury of the nerves in the lower neck and supraclavicular fossa caused by excessive extension and manipulation.

Right-sided predominance:

RPS may be more common on the right side than the left. This is thought to be due to anatomical asymmetry on the right side, such as the right recurrent laryngeal nerve looping under the right subclavian artery and the right phrenic nerve crossing the right subclavian artery (see “Pathophysiology” section for details).

When to see a doctor

If hoarseness persists for more than 2 weeks, or if you notice eye abnormalities such as drooping eyelid or constricted pupil, seek medical attention promptly. Early consultation is especially important for those with a history of smoking or a personal or family history of malignancy.

Q Why might this syndrome be more common on the right side?

A

Anatomical asymmetry related to the right subclavian artery is considered the reason. The right recurrent laryngeal nerve, right phrenic nerve, and the right subclavian loop of the sympathetic trunk all run close to the right subclavian artery, so a lesion in that area can easily affect all three nerves simultaneously.

4. Diagnosis and Examination Methods

The diagnosis of RPS involves confirming the triad of Horner syndrome, vocal cord paralysis, and diaphragmatic paralysis, and then searching for an underlying disease that can explain these findings.

Confirmation of Horner Syndrome

Pharmacological Testing

Apraclonidine eye drops: Due to denervation supersensitivity, the pupil on the affected side dilates, causing “reverse anisocoria” compared to the healthy side. Useful for diagnosing Horner syndrome.

Cocaine eye drops: A classic test to confirm Horner syndrome by observing that the affected pupil does not dilate.

Imaging Tests

Brain MRI: To rule out intracranial lesions.

Cervical and upper thoracic MRI: To evaluate the entire oculosympathetic pathway.

Cervical CTA/MRA: To search for vascular lesions (e.g., carotid artery dissection).

Evaluation of Vocal Cord Paralysis and Diaphragmatic Paralysis

• Laryngeal fiberscopy: Confirmation of vocal cord paralysis.
• Chest X-ray: Confirm elevation of the diaphragm on the affected side.

Search for Underlying Diseases

• If a neoplasm is suspected, perform a detailed examination including biopsy.
• PET-CT or chest/abdominal CT is used to search for masses.

Differential Diagnosis

Other diseases that cause Horner syndrome need to be ruled out, including the following.

• Carotid artery dissection/thrombosis
• Intracranial lesions/demyelinating diseases
• Spinal cord lesions/cervical disc herniation
• Brachial plexus injury/pneumothorax
• Raeder paratrigeminal syndrome / temporal arteritis
• Herpes zoster / migraine

Differential diagnosis should also be pursued in parallel for causes of vocal cord paralysis or unilateral diaphragmatic paralysis (e.g., iatrogenic injury, trauma, infection).

5. Standard Treatment

There is no specific treatment for RPS. The mainstay of treatment is the curative therapy of the underlying disease.

When caused by malignant tumor: Surgery, chemotherapy, or radiation therapy is selected according to the type and stage of the tumor. If the compression or infiltration of the nerve by the tumor is resolved, neurological symptoms may improve.

When caused by infection: For tuberculous lymphadenitis, antituberculosis therapy is the mainstay; for empyema, antibiotic treatment and drainage are fundamental.

Prognosis: It largely depends on the type of underlying disease and response to treatment. In malignant tumors, the stage of the primary disease and overall condition determine the prognosis.

Importance of prompt investigation of the cause

RPS itself is an important clinical sign indicating the presence of a serious underlying disease (especially malignant tumors). Once the syndrome is diagnosed, it is essential to promptly start a thorough search for the cause.

6. Pathophysiology and detailed mechanism of onset

Anatomical basis

The onset of RPS is based on the anatomical characteristic that three different nerves run close together in a narrow region of the neck and upper chest.

At the level of the sixth cervical vertebra, the cervical sympathetic trunk, vagus nerve (which branches into the recurrent laryngeal nerve), and phrenic nerve run almost adjacent to each other in a very narrow area behind the carotid sheath, anterolateral to the anterior scalene muscle, and anteromedial to the jugular lymph nodes. Therefore, a single lesion in this area can simultaneously damage all three nerves ¹⁴.

At levels other than the sixth cervical vertebra, lesions may be located more caudally in the lower neck or thoracic inlet. At the thoracic inlet, a large lesion can expand to reach all three nerves.

Oculosympathetic Pathway (3-Neuron Chain)

The oculosympathetic pathway underlying Horner syndrome consists of three neurons.

1. First neuron (central): Descends from the hypothalamus through the brainstem and spinal cord.
2. Second neuron (preganglionic): Synapses at the ciliospinal center in the lower cervical and upper thoracic spinal cord, then travels to the superior cervical ganglion.
3. Third neuron (postganglionic): Ascends from the superior cervical ganglion along the carotid artery, passes through the long ciliary nerve, and distributes to the iris dilator muscle and Müller’s muscle (upper eyelid).

In RPS, the second neuron (preganglionic) is primarily affected. Miosis, ptosis, and anhidrosis result from blockade of this pathway.

Anatomical Basis for Right-Side Predominance

Possible anatomical reasons why RPS may occur more frequently on the right side include the following.

• The right recurrent laryngeal nerve loops under the right subclavian artery (the left recurrent laryngeal nerve loops lower around the aortic arch, thus distributing over a wider area).
• The right phrenic nerve crosses the right subclavian artery.
• The right subclavian ansa (ansa subclavius) of the sympathetic trunk also passes under the right subclavian artery.

This anatomical asymmetry makes it easier for lesions near the right subclavian artery to simultaneously affect the three nerves.

Mechanism of neonatal RPS

It is speculated that excessive stretching and manipulation during forceps delivery cause mechanical shear injury to the nerves running through the lower neck and supraclavicular fossa. This is noted as the only form without a structural mass lesion.

Q Why can a single lesion simultaneously damage three different nerves?

A

At the level of the sixth cervical vertebra, the cervical sympathetic nerve, vagus nerve (recurrent laryngeal nerve), and phrenic nerve run adjacent to each other in a very narrow area behind the carotid sheath. When a mass, inflammation, or trauma occurs in this anatomical accumulation site, all three nerves are affected together.

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8. References

Footnotes

1. Amin R. Horner’s syndrome with ipsilateral vocal cord and phrenic nerve palsies. Postgrad Med J. 1984;60(700):140-142. doi:10.1136/pgmj.60.700.140. PMID: 6709546; PMCID: PMC2417696. https://pubmed.ncbi.nlm.nih.gov/6709546/ ↩ ↩² ↩³

2. Nieporęcki K, Szczudlik P, Lipowska M, Rosiak E, Kuźma-Kozakiewicz M. Rowland Payne syndrome mimicking motor neuron disease. Neurol Neurochir Pol. 2025;59(3):302-305. doi:10.5603/pjnns.103859. PMID: 40241640. https://pubmed.ncbi.nlm.nih.gov/40241640/ ↩ ↩² ↩³ ↩⁴

3. Kapoor V, Lodha R, Agarwala S. Superior mediastinal syndrome with Rowland-Payne syndrome: an unusual presentation of cervico-mediastinal neuroblastoma. Pediatr Blood Cancer. 2005;44(3):280-282. PMID: 15503296. https://pubmed.ncbi.nlm.nih.gov/15503296/ ↩

4. Sierra-Hidalgo F, Aragón Revilla E. Rowland Payne syndrome. Neurologia (Engl Ed). 2021;36(9):734-736. doi:10.1016/j.nrleng.2021.02.002. PMID: 34266796. https://pubmed.ncbi.nlm.nih.gov/34266796/ ↩ ↩²