What tests should be done for a 3-year-old patient with Harlequin syndrome, alternating and intermittent Horner's (Horner syndrome) syndrome, and Short-lasting Unilateral Neuralgiform headache with Conjunctival injection and Tearing (SUNCT)?

Diagnostic Evaluation for a 3-Year-Old with Harlequin Syndrome, Alternating Horner's Syndrome, and SUNCT

MRI with gadolinium of the brain, neck, and thorax with MRA is the most critical diagnostic test for this child with this rare combination of neurological disorders, as it could reveal a potentially serious underlying cause requiring urgent intervention. 1

Understanding the Clinical Presentation

This 3-year-old presents with three rare neurological conditions:

1. Harlequin syndrome: Unilateral facial flushing and hyperhidrosis, typically in response to exercise, heat, or emotional stress
2. Alternating and intermittent Horner's syndrome: Characterized by ptosis, miosis, and potentially anhidrosis that switches sides
3. SUNCT (Short-lasting Unilateral Neuralgiform headache with Conjunctival injection and Tearing): Brief, severe headaches with autonomic features

This combination is extremely rare, especially in pediatric patients, and strongly suggests a structural lesion affecting the sympathetic pathways.

Diagnostic Algorithm

Immediate Neuroimaging

• MRI with gadolinium of brain, neck, and thorax with MRA 1
  • Focus on brainstem, cervical spine, and thoracic sympathetic chain
  • Evaluate for mass lesions, vascular abnormalities, or demyelination
  • Special attention to paravertebral thoracic region and apex of lung 2

Ophthalmologic Evaluation

• Complete ophthalmic examination with emphasis on:
  • Pupillary assessment (size, symmetry, reactivity) 3
  • Sensorimotor evaluation 3
  • Funduscopic examination to check for papilledema or optic atrophy 3
  • Documentation of preferred head posture 3

Autonomic Function Testing

• Pharmacological testing of pupils:
  • Cocaine test (confirms Horner's syndrome)
  • Hydroxyamphetamine test (localizes lesion)
• Sweat testing to document anhidrosis pattern

Additional Testing Based on Initial Results

• Cerebrospinal fluid analysis if MRI suggests demyelination or inflammation
• CT scan of chest to evaluate for thoracic pathology if MRI is inconclusive
• Video EEG monitoring if seizure activity is suspected

Clinical Considerations

Localization of Lesion

The combination of these symptoms suggests potential involvement of:

• Brainstem: Could explain SUNCT and alternating Horner's syndrome 3
• Cervical/thoracic sympathetic chain: Could explain Harlequin syndrome 4

Potential Etiologies

1. Structural lesions:

   • Schwannoma (particularly concerning in pediatric patients) 5
   • Other neurogenic tumors affecting sympathetic pathways 5
   • Vascular malformations

2. Inflammatory/demyelinating conditions:

   • Multiple sclerosis (rare in this age group but possible)
   • ADEM (Acute Disseminated Encephalomyelitis)

3. Post-infectious dysautonomia:

   • Viral infections affecting autonomic pathways 4

4. Congenital abnormalities:

   • Developmental anomalies of sympathetic pathways 6

Important Considerations

• The alternating nature of the Horner's syndrome is particularly concerning and unusual, suggesting a dynamic process or multiple lesions
• The association between SUNCT and Horner's syndrome has been reported but is extremely rare 7
• Approximately half of Harlequin syndrome cases are complicated with ocular symptoms 4
• This combination of symptoms may represent part of a more extensive partial dysautonomia 4

Multidisciplinary Approach

Given the complexity and rarity of this presentation, consultation with:

• Pediatric neurologist
• Neuro-ophthalmologist
• Pediatric neurosurgeon (if structural lesion identified)
• Otolaryngologist (for evaluation of potential head and neck pathology) 3

Pitfalls to Avoid

• Do not assume idiopathic etiology despite Harlequin syndrome often being benign, as the combination with alternating Horner's syndrome and SUNCT strongly suggests secondary pathology
• Do not delay neuroimaging as early detection of structural lesions is critical for preventing permanent neurological damage 6
• Do not focus solely on one syndrome - the combination provides important localizing value
• Do not overlook subtle signs of increased intracranial pressure or other neurological deficits

The presence of this triad of rare neurological disorders in a 3-year-old child warrants urgent and comprehensive evaluation, with neuroimaging being the cornerstone of the diagnostic approach.