GRAND ROUNDSDesiree Ong, M.D.

Vanderbilt Eye Institute

12/15/06

Our Patient

• 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.

History

• 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

Exam

• 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

Exam continued

• 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

Sympathetic Pathway

Differential diagnosis?Acquired Pediatric Horner Syndrome

Differential DiagnosisAcquired Pediatric Horner Syndrome

• 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

Lab Results

• 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

Horner Syndrome• 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

Other associations• 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

Testing• No standard evaluation protocol

• Previous studies suggested that a h/o birth trauma or urine studies alone is sufficient3

• CBC, FTA-ABS, VDRL, PPD

• VMA and HVA urine tests– positive in 90-95% with neuroblastomas– localized tumors may be associated with normal urine

studies2

• MRI/MRA, extracranial Doppler, and/or chest x-ray

Testing

• 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

Chen et al. (2006)

• 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.

Testing

• 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

Mahoney et al. (2006)• 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 spotMahoney 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

Cervical Lymphadenopathy in Children

• 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

Cervical Lymphadenopathy in Children

• 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

Cervical Lymphadenopathy

Oguz et al. (2006)

- 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.

Our Patient

• 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

Take Home Points

• 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

References1. 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.

2. 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.

3. George ND, Gonzalez G, Hoyt CS. Does Horner's syndrome in infancy require investigation? J Ophthalmol. 1998 Jan;82(1):51-4

4. Leung AK, Robson WL. Childhood cervical lymphadenopathy. J Pediatr Health Care. 2004 Jan-Feb;18(1):3-7

5. 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

6. Oguz A and Karadeniz C. Evaluation of Peripheral Lymphadenopathy in Children. Pediatric Hematology and Oncology. 23:549-561, 2006.

7. Sauer C, Levingohn MW. Horner's syndrome in childhood. Neurology. 1976 Mar;26(3):216-20

8. Twist CJ. Assessment of lymphadenopathy in children. Pediatr Clin North Am 2002;49(5):1009-1025.

9. Yaris N et al. Analysis of Children with Peripheral lymphadenopathy. Clinical Pediatrics. 2006;45:544-549.