Horner's syndrome in children and apraclonidine

Horner's syndrome in children often manifests itself with theanisocoriawhich consists of an abnormality in the size of the pupils of the eyes, which should normally be the same size and react similarly to light

In recent years, the off-label topical use of the apraclonidine, an α-2 adrenergic agonist, has transformed the diagnostic approach in young patients with Horner's syndrome, allowing rapid confirmation of pathology without invasive investigations. However, the safety of the use of this substance in paediatric age remains a critical issue, as there appears to be a risk of systemic side effects in very young children.

In this article we will take an in-depth look at the benefits, limitations and potential complications of apraclonidine use, providing a comprehensive framework for dealing with this delicate condition in paediatric settings.

Introduction to Horner's Syndrome

Horner's syndrome, also known as Bernard-Horner's syndrome, is a dysfunction of the autonomic nervous system linked to a complete or partial interruption of the sympathetic pathways, which are responsible for the involuntary control of various ocular and facial functions. The interruption of these pathways can occur at various levels, leading to the clinical manifestations typical of the syndrome.

Recognising it early in children is crucial because, unlike in adults, it can signal even very serious or developmental pathologies.

Main Symptoms

Horner's syndrome is a neurological condition characterised by a triad of oculopalpebral clinical signs, occurring unilaterally:

• Mild eyelid ptosis, i.e. lowering of the upper eyelid, due to paralysis of the Müller tarsal muscle, which is innervated by the sympathetic system. As this muscle contributes to the maintenance of the eyelid opening, its dysfunction leads to partial closure of the eye.
• miosisi.e. the constant narrowing of the pupil on the affected side due to paralysis of the iris dilator muscle, which is also under sympathetic control. This dysfunction leads to a reduction in pupil diameter, irrespective of lighting conditions.
• Anhidrosis: i.e. the reduction or absence of sweating on the affected side of the face, which occurs when the lesion involves the sympathetic fibres innervating the sweat glands. This symptom is most evident in lesions occurring below the carotid bifurcation.

In addition to the triad of classical clinical signs, ocular signs may occur:

• Apparent endophthalmos: whereby the eyeball may appear slightly recessed in the orbit, giving the impression of a more sunken eye.
• Conjunctival hyperemia: due to increased blood flow in the conjunctiva, resulting in redness of the eye.

These signs are important indicators of abnormal functioning of the sympathetic nervous system. In children, it is also particularly important to consider any changes in iris colour (heterochromia) since, if the sympathetic damage is early, the eye may develop lighter pigmentation.

Timely diagnosis allows rapid investigation of potentially serious causes.

Syndrome Causes and Diagnosis

Causes of Horner's syndrome in children may include:

• birth traumaoften associated with brachial plexus injuries
• masses or tumourssuch as cervical or thoracic neuroblastomas
• recent surgeriesespecially on neck and chest
• vascular alterationse.g. carotid dissections
• idiopathic causesmore rare but possible

To identify the origin of the damage, the following are often used MRI brain/neck/thoraxultrasounds and other targeted analyses.

Clinical diagnosis is based on observation of symptoms, but the use of pharmacological tests, including apraclonidine, can offer rapid confirmation, avoiding more invasive initial procedures.

Apraclonidine: mechanism of action

Apraclonidine is an adrenergic agonist with strong α2 and weak α1 activity, capable of reversing the anisocoria typical of Horner's syndrome. In Horner's syndrome patients, postsynaptic receptors become hypersensitive due to sympathetic denervation.

This leads to a characteristic effect:

• in the normal pupil: mild constriction is observed
• in the affected pupil: marked dilatation is observed

The result is a reversal of anisocoria within 30-60 minutes, which is a very reliable diagnostic sign.

The test is, therefore, useful not only to confirm the syndrome, but also to distinguish physiological anisocoria from pathological causes.

Use in Children with Anisocoria

In children, especially infants, apraclonidine is used off-label, as it is not officially approved for paediatric use in diagnosing Horner's syndrome.

The main advantages include:

• rapid diagnosis with no immediate need for advanced imaging
• stress reduction for the child
• high test reliability

However, young patients, particularly under two years of age, are much more sensitive to the systemic effects of the drug, and even a small dose can produce major undesirable reactions. For this reason, use must be carefully evaluated and accompanied by close monitoring.

Systemic Toxicity and Side Effects

The main concern relates to the systemic toxicitydue to the absorption of the drug through the nasal mucosa and conjunctiva. In infants and young children, the systemic barrier is less efficient, increasing the risk of significant side effects.

The most reported symptoms include:

• prolonged lethargy
• hypothermia
• bradycardia
• hypotension
• shallow or slowed breathing
• marked drowsiness and difficulty waking up

These reactions require immediate medical intervention and often hospital observation.

Data and Case Study Analysis

A clinical study on 21 children treated with apraclonidine to confirm Horner's syndrome reported highly relevant data:

• 81% developed significant lethargy
• some cases have required observation or admission
• For 3 children, theintubation
• symptoms appeared within a few hours from the application

This evidence clearly shows that apraclonidine has a high risk profile in the most vulnerable paediatric patients.

Prevention and Monitoring of Side Effects

Strategies to reduce risk include:

• use of the minimum effective dose
• tear point compression (tip occlusion) to reduce systemic absorption
• monitoring the child for at least 2-3 hours after application
• clear instructions to parents on which symptoms to observe

Informing the family thoroughly is a key part of the process: awareness of possible warning signs can prevent severe complications.

Recommendations for Health Professionals

Healthcare professionals must follow up-to-date guidelines and maintain active communication with parents.

This is important:

• document the use of the drug in detail
• report any adverse reactions
• assessing diagnostic alternatives when the risks outweigh the benefits
• consider the age of the child as a critical factor

Continuing education and updating clinical skills are essential tools for improving daily paediatric practice.

Conclusions and Future Perspectives

Horner's syndrome in children requires a rapid, but above all safe diagnostic approach. Apraclonidine is a valuable tool, but not without significant risks. Knowing the benefits and potential complications allows doctors and parents to make more informed decisions.

Importance of Early Diagnosis

Early diagnosis enables the early detection of possible neurological or tumour causes, early intervention and prevention of complications. Physicians must, therefore, maintain a high level of suspicion and act quickly when signs are present.

Implications for Paediatric Clinical Practice

The experience with apraclonidine teaches how crucial careful risk management is in paediatrics. Those who care for children must balance diagnostic efficacy and safety, adopting appropriate protocols and communicating transparently with families.

As studies and guidelines progress, safer and more specific diagnostic approaches are likely to emerge, further improving the care of children with Horner's syndrome.

• Gish P, Kim I, Kapoor R, Jones SC. Systemic Toxicity With Use of Apraclonidine Ophthalmic Drops in Paediatric Patients. JAMA Ophthalmol. Published online November 06, 2025. doi:10.1001/jamaophthalmol.2025.4243
• Eldib AA, Patil P, Nischal KK, et al. Safety of apraclonidine eye drops in diagnosis of Horner syndrome in an outpatient paediatric ophthalmology clinic. J AAPOS. 2021 Dec;25(6):336.e1-336.e4. doi: 10.1016/j.jaapos.2021.07.011.