Desiree Ong, M.D.
Vanderbilt Eye Institute
12/15/06

• CC: “Droopy eyelid”
• HPI: 7 mo old male with unequal pupil size x 3 days noted by mother. Pt was evaluated at an outside ER, head CT was negative. Over the next 24 hrs, mother noticed that left eyelid began to droop.

• POHx: none
• PMHx: full-term, normal birthweight, no complications
• FHx: no eye disease, healthy 6 yo sibling
• Social hx: non-contributory
• Allergies: NKDA
• Meds: none

• VA: Fixes and follows
• Pupils: OD bright 4-->3mm dim 5.5-->4.5mm
OS bright 2.5-->2mm dim 2-->1.5mm
• Motility: grossly full OU
• Tp: soft to palpation OU

• PLE
– External: palpebral fissure OD 9mm, OS 6mm, small movable cervical nodes left>right
– Lids/lashes: quiet OU, mild ptosis OS
– S/C: quiet OU
– K: quiet OU
– A/C: formed OU
– Iris: intact OU
– Lens: clear OU
• DFE
– WNL OU, C/D 0.2 OU

• First-order lesions (hypothalamus to C8-T2)
– Meningitis
– Basal skull tumors, pituitary tumor
– Brain stem vascular malformation
– Cerebral vascular accident
– Demyelinating disease
– Intrapontine hemorrhage
– Neck trauma/cervical disk disease
• Second-order (preganglionic) lesions (T1 to SCG)
– Neuroblastoma
– Lymphadenopathy (reactive or malignant)
– Apical lung tumors
– Metastases
– Mandibular tooth abscess
– Lesions of the middle ear (eg, acute otitis media)
– Thyroid adenoma
– Thoracic aorta, subclavian or common carotid artery aneurysm
– Trauma/surgical injury/chest tube/central venous catheter

• Third-order lesions (SCG to post-ganglionic neurons)
– Internal carotid dissection/aneurysm/vasopasm
– Extension of cavernous sinus tumor, nasopharyngeal tumor
– Carotid cavernous fistula
– Cluster/migraine headaches
– Herpes zoster
– Otitis media
– Neck trauma/tumor (i.e. rhabdomyosarcoma)/inflammation
• Drugs
– Bupivacaine
– Chlorprocaine
– Chlorpromazine
– Deserpidine
– Diacetylmorphine
– Diethazine
– Fluphenazine
– Guanethidine
– Influenza virus vaccine
– Levodopa
- Lidocaine
- Mepivacaine
- Mesoridazine
- Oral contraceptives
- Procaine
- Prochlorperazine
- Promethazine
- Propoxycaine
- Reserpine
- Thioridazine

• Pt was admitted for observation
• CXR: negative
• MRI/CT brain/chest/abdomen: negative
• CBC, CMP, HVA/VMA urine tests were
WNL
• LDH was elevated at 552

• Ptosis denervation of Müller muscle
• “Reverse ptosis” - lower lid elevation
• Miosis - greater in dim light (dilation lag)
• Anhidrosis – impaired flushing and sweating
– First-order: ipsilateral body
– Second-order: ipsilateral face
– Post-ganglionic (third-order): absent or limited
• Iris heterochromia – affected iris is lighter
- Congenital or children < 2 yrs
- Long-standing lesions

• First-order lesions :
– Hemisensory loss, weakness, dysarthria, dysphagia, ataxia, vertigo, and nystagmus
• Second-order lesions :
– H/o trauma/surgery, facial/neck, axillary/shoulder or arm pain/swelling, cough, hemoptysis
• Third-order lesions :
– Diplopia (CN VI palsy), numbness/pain in V1 and V2
• Cluster headaches
– may cause temporary or permanent Horner syndrome

• No standard evaluation protocol
• Previous studies suggested that a h/o birth trauma or urine studies alone is sufficient 3
• CBC, FTA-ABS, VDRL, PPD
• VMA and HVA urine tests
– positive in 90-95% with neuroblastomas
– localized tumors may be associated with normal urine studies 2
• MRI/MRA, extracranial Doppler, and/or chest x-ray

• Cocaine (4% or 10%)
– Inhibits the re-uptake of norepinephrine
– Denervation  poor dilation regardless of level
– Anisocoria greater than 0.8 mm = positive
• Apraclonidine (0.5% or 1%)
– Alpha-receptor agonist
– Denervation supersensitivity of the iris dilator
– Reversal of anisocoria = positive

• Small randomized crossover study (10 pts)
• Testing with 0.5% apraclonidine and 4% cocaine
• Mean differences in pupil diameter
-before/after 4% cocaine = -2.08/-2.97 mm
(p=0.0047)
-before/after 0.5% apraclonidine = -2.04/+1.08 mm (p=0.005)
• Conjunctival hyperemia in two patients
• Conclusion: 0.5% apraclonidine is safe and effective for diagnosis of Horner syndrome in children
Chen PL, Chen JT, Lu DW, Chen YC, Hsiao CH. Comparing efficacies of 0.5% apraclonidine with 4% cocaine in the diagnosis of Horner syndrome in pediatric patients. J Ocul Pharmacol Ther. 2006 Jun;22(3):182-7.

• Hydroxyamphetamine 1% (Paredrine)
– Stimulates presynaptic norepinephrine release
– Distinguishes presynaptic from postganglionic lesions
– 40-97% sensitive; inaccurate within 24-48 hours of cocaine test
– Failure of affected pupil to dilate equally or greater to normal pupil = third-order lesion

• Retrospective review (56 children)
• 28 (50%) had no previously identified cause
- 18 with complete imaging and urine studies
- Mass lesions found in 6/18 (33%); 4 had neuroblastoma; all negative urine studies
• Of all patients, 13/56 had a neoplasm (23%)
• Conclusions:
- Urine testing alone is inadequate
- Recommend physical exam with palpation
- MRI brain/neck/chest, VMA and HVA by spot
Mahoney NR, Liu GT, Menacker SJ, Wilson MC, Hogarty MD, Maris JM. Pediatric Horner syndrome: etiologies and roles of imaging and urine studies to detect neuroblastoma and other responsible mass lesions. Am J Ophthalmol. 2006 Oct;142(4):651-9

• Acute bilateral - adenovirus, influenza, RSV; EBV and CMV
• Acute unilateral - strep or staph (40-80%)
• Indications for biopsy:
- Persistent enlargement
- Solid fixed or supraclavicular mass
- Constitutional signs and symptoms
• Increased risk for malignancy: 8
- Generalized LAD
- LAD > 3 cm
- Hepatosplenomegaly
- High LDH levels

• Subacute/chronic LAD
– Cat scratch, mycobacteria, and toxoplasmosis
– EBV, CMV, histoplasmosis, HIV
– Leukemia, lymphoma, neuroblastoma, rhabdomyosarcoma, and nasopharyngeal carcinoma
• Laboratory tests are not necessary in majority
• Most cases are self-limited and require no treatment

- Retrospective review
- 457 children aged 2 mo -19 yrs
- 76% benign, 24% malignant
- 61% of the benign group had an unknown etiology
- Most common benign etiologies: EBV and acute lymphadenitis
Most common malignant: Hodgkin’s and NHL
- None in the infant group had a malignant process
Oguz A and Karadeniz C. Evaluation of Peripheral Lymphadenopathy in Children. Pediatric
Hematology and Oncology. 23:549-561, 2006.

• Started on Unasyn
• Improvement was noted over the next few days
• Repeat CT showed decreased necrosis
• Persistent Horner syndrome, monitored closely
• Recently started on 10 days of Omnicef for a persistent otitis media/URI

• Horner syndrome may be the first symptom of a potentially serious condition
• Children with Horner syndrome should undergo a thorough physical exam with urine testing and
MRI
• Acute cervical lymphadenopathy in children usually has an infectious cause but should be monitored closely

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Chen PL, Chen JT, Lu DW, Chen YC, Hsiao CH. Comparing efficacies of 0.5% apraclonidine with 4% cocaine in the diagnosis of Horner syndrome in pediatric patients. J Ocul Pharmacol Ther. 2006 Jun;22(3):182-7.
Fritsch P, Kerbl R, Lackner H, et al. “Wait and see” strategy in localized neuroblastoma in infants: an option not only for cases detected by mass screening.
Pediatr Blood Cancer 2004;43:679-682.
George ND, Gonzalez G, Hoyt CS. Does Horner's syndrome in infancy require investigation? J Ophthalmol. 1998 Jan;82(1):51-4
Leung AK, Robson WL. Childhood cervical lymphadenopathy. J Pediatr Health Care.
2004 Jan-Feb;18(1):3-7
Mahoney NR, Liu GT, Menacker SJ, Wilson MC, Hogarty MD, Maris JM. Pediatric horner syndrome: etiologies and roles of imaging and urine studies to detect neuroblastoma and other responsible mass lesions. Am J Ophthalmol. 2006
Oct;142(4):651-9
Oguz A and Karadeniz C. Evaluation of Peripheral Lymphadenopathy in Children.
Pediatric Hematology and Oncology. 23:549-561, 2006.
Sauer C, Levingohn MW. Horner's syndrome in childhood. Neurology. 1976
Mar;26(3):216-20
Twist CJ. Assessment of lymphadenopathy in children. Pediatr Clin North Am
2002;49(5):1009-1025.
Yaris N et al. Analysis of Children with Peripheral lymphadenopathy. Clinical
Pediatrics. 2006;45:544-549.