Grand Rounds Conference
Lara Rosenwasser Newman, MD
University of Louisville
Department of Ophthalmology and Visual Sciences
October 2, 2015
Patient 1 - Subjective

CC: unequal pupils (anisocoria)

HPI: 4 month old male in whom pediatrician
and parents noted unequal pupils
History

POH: None

PMH: born via spontaneous vaginal delivery at
home, complicated by no prenatal care (mother
did not know she was pregnant), nuchal cord x2

Eye Meds: None
Meds: none
Allergies: NKDA


Objective
BCVA:
Pupils:
IOP:
EOM:
OD
CSM
6->4
soft
full OU
OS
CSM
5->3
soft
Objective
SLE:
OD
OS
External/Lids
WNL
mild ptosis, 1-2 mm
Conjunctiva/Sclera
clear/white
clear/white
Cornea
clear
clear
Anterior Chamber
formed
formed
Iris
increased brown pigment
less brown pigment
Lens
clear
clear
DFE
ON pink/sharp, M/V/P WNL OU
Clinical Photo
Impression & Plan

Horner syndrome OS
Decreased iris pigmentation OS
 Ptosis OS, 1-2 mm
 Miosis OS vs OD


Likely congenital


Still could be acquired in a 4 month old
Ordered MRI head/neck/chest
Patient 2



CC: “unequal pupil size and clogged tear ducts”
HPI: 6 month old girl with OD pupil larger than
OS, drainage OU, OD draining more and yellow
Exam: vision CSM OU
Pupils 6.5 OD and 4.5 OS in dark, 2.5 OU in light
 Dilation lag OS


MRI head/neck/chest ordered
DDx of Anisocoria in Children

Physiologic anisocoria: Usually <1 mm, can vary day to day,
inequality does not change with bright/dim light

Tonic pupil: greater in bright light, sluggish, segmentally
responsive to light, more responsive at near

Horner syndrome: greater in dim light, associated ptosis
miosis
Horner• Pupillary
Syndrome
• Facial anhidrosis

AKA oculosympathetic palsy

Clinical picture: Ptosis, miosis, and anhidrosis


Congenital cases associated with iris heterochromia
Due to disturbance somewhere along sympathetic
pathway to dilator pupillae muscle and ciliary body
Central or 1st order:
• Hypothalamus
• Brainstem
• Cervical spinal cord
Terminates at ciliospinal center
of Budge between C8-T2
Pre-ganglionic or 2nd order:
• Spinal cord, cervical/thoracic
• Brachial plexus
• Pleural apex
Post-ganglionic or 3rd order:
• Superior cervical ganglion
• Cavernous sinus
• Internal carotid artery
• Joins ophthalmic division of
trigeminal nerve
Diagnosis and Localization

Diagnose with topical cocaine or apraclonidine



Cocaine dilates unaffected eye, no effect on affected eye
Apraclonidine has little effect on normal pupils, but dilates
sympathetically denervated/hypersensitive eyes
Localize with topical hydroxyamphetamine



Enhances release of NE from intact 3rd order neuron
Pupil does not dilate: suspect 3rd order lesion
Pupil dilates: 1st or 2nd order
First Order Causes of Horner’s

Lateralpresents
Medullary
Most commonly
as partSyndrome
of lateral
(Wallenberg
Syndrome)
medullary syndrome
or Wallenberg
syndrome


Infarction in lateral medulla in brainstem leads to
Infarction
ataxia,• vertigo,
Horner’s
• Ataxia
Other central
causes:
•
Vertigo
 Trauma
• Horner’s
 Demyelination
Syndrome
Cord neoplasm
 Syringomyelia

Second Order
Causes
Preganglionic

Trauma:



Birth
Iatrogenic
Chest tube
Surgery
birth, iatrogenic (chest tube, surgery)
Tumors:

Trauma
Tumor
Mediastinal
Lung
Vertebral / Rib
mediastinal, lung, vertebral, rib
Other: infectious, vascular, thyroid
mass, thoracic aortic aneurysm,
brachial plexus trauma
PNET
Third Order Sites/Causes

Carotid space – carotid artery, internal jugular vein, lymph nodes

Neoplasm at skull base, cavernous sinus, nasopharynx

Infections including:
Otitis media
 Lemierre syndrome: acute pharyngitis due to
Fusobacterium necrophorum, leading to septic
thrombophlebitis of internal jugular


Foreign body
rd
3
order Horner’s with pain

Cluster headaches

Raeder paratrigeminal syndrome

Carotid artery dissection


Pain in temple, orbit, sometimes throat
Get MRA
Pediatric Carotid Space Masses





Neuroblastoma
Neurofibroma
Schwannoma
Myofibrous tumors
Paraganglioma (rare)
What to image




Hypothalamus
Brainstem
Brachial plexus
Lung apex




Carotid space
Skull base
Cavernous sinus
Orbital apex
Order: MRI head, neck, and chest with and without contrast
Hedlund, Gary. Imaging the Pediatric Patient with Horner’s Syndrome.
Medicine.utah.edu/radiology conferences/Friday/62-HedlundHornerSynd.pdf
Patient 2 MRI results

MRI brain: Nonspecific bilateral otomastoid disease, congestive vs
inflammatory, otherwise WNL

MRI Neck: “small paraspinal mass at L lung apex adjacent to T1 and T2
vertebral bodies… abuts vertebral bodies without evidence of osseous
invasion or neural foramina involvement… measures approx 1.2 cm (TR) x
1.6 cm (AP) x 2.2 cm (SI)… most suggestive of the
ganglioneuroma/neuroblastoma spectrum given the history of Horner's
syndrome.


Small lymph nodes are visualized in the jugular chain bilaterally consistent with benign
reactive disease.
MRI Chest: “Enhancing solid lesion left posterior mediastinum/paraspinal
location at C7-T2. Measuring approximately 2.2 cm craniocaudally x 1.2 cm
medial laterally x 1.6 cm anteroposterior. Likely represents a
neuroblastoma/similar etiology. Within study limits, no definite spinal
extension. However study was not dedicated to evaluate the spine.”
MRI Chest
Patient 2 - Course

Underwent resection of L apical lung tumor via videoassisted thoracoscopy 19 days after presentation to
ophthalmologist

Op note: purplish mass at lung apex, appearing to arise
from 2 most cephalad superior ganglia
 Posteriorly connected to sympathetic chain


Had to divide sympathetic chain, remove ganglia
A few small nodes removed with the specimen
Patient 2 - Pathology






Neuroblastoma – favorable histology
Poorly differentiated
Margins involved – “minimal periganglion soft
tissue margin positive”
Extent: extracapillary extension without adjacent
organ involvement
6/6 adherent lymph nodes positive for tumor
MYCN gene negative
Patient 2 - Immunophenotyping

Discrete population of large cells negative for
CD3, CD19, CD45, brightly positive for CD56

Consistent with non-hematopoietic malignancy

Bright CD56 positivity: suggestive of
neuroendocrine origin

Retrospective chart review of 56 children seen for Horner
Syndrome 1993-2005 @ UPenn



Of 18 who had both urine studies and imaging, 33% (6) had
responsible mass lesions found


24 had urine catecholamine metabolite studies (all negative results)
20 had complete modern imaging (brain/neck/chest)
Neuroblastoma (4), Ewing sarcoma (1), juvenile xanthogranuloma (1)
Conclusion: recommend MRI brain, neck, chest with and
without contrast and urine studies (imaging more sensitive)
Two cases of 6-month olds

Patient 23: parents thought lid abnormality present
since 2 wks old, maybe since birth



MRI w/right apical lung mass
Stage 2A neuroblastoma resected
Patient 24: anisocoria and ptosis, vacuum extraction at
birth, lid “swelling” noted by parents at 4.5 months



MRI with cervical lymph node
Repeat MRI 3 months later  node larger
Stage 3 intermediate risk neuroblastoma resected
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
References
1.
BCSC: Pediatric Ophthalmology and Strabismus (Section 6)
2.
BCSC: Neuro-ophthalmology (section 5)
3.
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. PubMed PMID: 17011859.
4.
Hedlund, Gary. Imaging the Pediatric Patient with Horner’s Syndrome.
Medicine.utah.edu/radiology conferences/Friday/62HedlundHornerSynd.pdf
5.
Kanski and Bowling’s Clinical Ophthalmology, 7th edition
THANK YOU
DDx of Pediatric Heterochromia

Hypochromic heterochromia:







Horner syndrome
Incontinentia pigmenti
(Bloch-Sulzberger syndrome)
Fuchs heterochromia
Waardenburg syndrome
Non-pigmented tumors
Hypomelanosis of Ito
Hyperchromic heterochromia:






Oculodermal melanocytosis
Pigmented tumors
Siderosis
Iris ectropion syndrome
Extensive rubeosis
Port-wine stain
Diagnosis of Horner Syndrome

Topical cocaine (4% or 10%):



Blocks re-uptake of norepinephrine released at sympathetic terminals in
the eye  dilation, lid retraction, conj blanching in unaffected eye
Affected eye: no norepinephrine secreted so no effect on pupil
Topical apraclonidine (0.5% or 1%), weak alpha-1 agonist:


Little effect on pupil size in most normal eyes
Iris dilator is supersensitive to adrenergics in sympathetically denervated
eyes  pupil in affected eye will dilate
Localization of lesion in Horner’s

Topical 1% hydroxyamphetamine:

Enhances release of presynaptic norepinephrine
from an intact 3rd order neuron

If pupil does not dilate: suspect 3rd order lesion

If both pupils dilate well, 1st or 2nd order lesion