Eye Have a Clue Timothy N. Booth MD Children's Health of Dallas, University of Texas Southwestern May 2018

1. Eye Have a Clue
Ophthalmologic indicators of CNS
pathology
Timothy N. Booth, M.D.
Department of Radiology
Pediatric Neuroradiology
Children’s Health of Dallas
University of Texas Southwestern

2. Objectives
• Appearance of…
– Optic nerve hypoplasia
– Optic excavations
– Optic nerve swelling
– Buphthalmos
• Intracranial associations
• Nystagmus, when to worry and where to look

3. Optic Nerve Hypoplasia
• Most common disc
anomaly
• Small optic disc (pale,
double ring)
Eyerounds.org

4. Clinical Issues with ON Hypoplasia
• Visual function
• Hypopituitarism
– Clinically difficult to
evaluate >6 m/o
– GHD, PHP, DI
– Risk of sudden death
• Related to corticotropin
deficiency
• Seizures, developmental
delay
1 m/o with ONH
11 m/o with ONH

5. MRI
• Confirmation or identification of ONH
• Coronal mid-aspect
– <6 months old, <.2mm abnormal
– >6 months old, <1.3mm abnormal
– Optic nerve does grow (2 years)
• Likely low sensitivity, have to be really
small
3 m/o, not tracking
Al-Haddad CE, et al. Optic nerve measurement on MRI in the pediatric
population: normative values and correlations. AJNR 2018; 39: 369-374
4 y/o, heroin

6. More Important is
Associated
Abnormalites!!
• Abnormal
migration
– Polymicrogyria
– Schizencephaly
• Hypoplastic
corpus callosum
• Intrauterine or
perinatal injury
2 y/o with ON hypoplasia

7. 5 m/o with bilateral ONH

8. • Associations – genetic or
ischemic
• Cerebral anomalies = poor
neurodevelopmental
outcome
Optic hypoplasia associations
Borchert, M. Reappraisal of the optic nerve hypoplasia syndrome. J Neuro Ophthal 2012; 32: 58-67
6 m/o with ONH

9. Other Associations
• PHACE
– Segmental facial IH
– IC anomalies
– Vascular anomalies
• MRA needed
• May be progressive
3 m/o S1,4 segmental IH, ONH
16 months later

10. 2 month old with ONH, IH, apnea

11. Segmental Optic Nerve Hypoplasia
• Usually superior disc
• Associations
– Maternal diabetes
– Destructive lesions
• PVL
• Porencephaly
6 y/o with bilateral ONH

12. Excavated Optic Disc Anomalies
• Distinct entities
– Morning glory disc anomaly
– Coloboma
– Peripapillary staphloma

13. MGDA
• aka “The moyamoya optic disc”
• Differentiating ophthalmologic findings
– MGDA incorporates the entire optic disc
– MGDA has abnormal vascularity
– Coloboma obliterates inferior portion
• 2 jobs
– Confirm or aid in diagnosis
– Look for associated abnormalities

14. MGDA
2 year old with optic disc anomaly
Ellika S et al. Morning Glory Disc Anomaly: Characteristic MR Imaging Findings. AJNR 2013: 34:2010
• MRI findings
– Funnel shaped ON head
– Retinal elevation
– Fat within the distal nerve
sheath
– Discontinuity of uveoscleral
coat
– Enhancement of the distal
ON
• Displaced choroid

15. MGDA Associations
• Transsphenoidal
encephalocele
– Clinical clues (often
overlooked)
• Obstructs airway
• Hypertelorism
• Small cleft in upper lip or
palate
– MRI
• Herniation of pituitary,
chiasm, ACAs
• Additional midline anomalies
2 year old with MGDA, panhypopituitarism

16. MGDA Associations
• Moyamoya
– Ipsilateral vascular
dysgenesis
– With or without
typical collaterals
– 45%, progressive
2 year old with left MGDA

17. MGDA Other Associations
• PHACE
– Ipsilateral
– Also
peripapillary
staphlomas
• NF2

18. Optic Disc Coloboma
• Ophthalmologic findings
– Bowl-shaped excavation
– Decentered inferiorly
– Can extend into adjacent
choroid/retina
– Associated other colobomas
• Defect resulting in failure of
choroidal fissure closure

19. Coloboma Associations
• Sporadic or AD
• Multiple associations
– CHARGE
– Walker-Warburg syndrome
– Aicardi syndrome
– Goltz focal dermal hypoplasia
– Linear sebaceous nevus syndrome
– Wolf-Hirschhorn syndrome
– Amniotic band – pseudo-coloboma
• Genetics – PAX6, CHX10, MAF, SHH, CHD7, GDF6,
SOX2

20. Newborn with respiratory distress
• 60% CHD7 mutation
• Usually sporadic
• Temporal bone
findings
– Absent SCCs and
small vestibule
– CN deficiency
– Cochlear dysplasia
Hoch MJ et al. Head and Neck MRI Findings in CHARGE Syndrome. AJNR 2017; 38: 2357
CHARGE
Association

21. Other CHARGE
Findings
13 d/o with SNHL, coloboma
• Olfactory anomalies
• Basioccipital hypoplasia
– Underdeveloped ossification
center
• Parotid absence or hypoplasia
• Venous anomalies
• CNS
– Brainstem, vermian
hypoplasia

22. Walker-Warburg
syndrome
• Clinical
– Severe form of CMD
• Defect in dystrophin glycoprotein
complex
– Multiple genetic mutations
• POMT1, POMT2, ISPD, FKTN…
– Eye abnormalities
• Coloboma
• Micropthalmia
• Cataracts
• PHPV

23. Walker-Warburg MRI
findings
• Diffuse cerebral cobblestone
cortex
• No myelination
• Callosal hypoplasia
• Posterior fossa
– Polymicrogyria with or without
cysts
– Hypoplastic pons and vermis
– Dorsal pontomesencephalic kink
Barkovich AJ. Neuroimaging Manifestations and Classification of Congenital Muscular Dystrophies. AJNT 1998; 19: 1389
11 m/o with decreased vision, DD

24. Aicardi Syndrome
• Clinical
– Infantile spasms
– Females (x-linked), XXY
males
– Eye abnormalities
• Coloboma
• Chorioretinal lacunae

25. Aicardi Syndrome
MRI findings
• Callosal dysgenesis
• Polymicrogyria
– Frontal and perisylvian
• Heterotopias (ST/IT)
• Intracranial cysts
– Interhemispheric > intraventricular
– May enhance
• Hypoplastic vermis
2 m/o with coloboma, hypotonia
Hopkins B et al. Neuroimaging Aspects of Aicardi Syndrome. Am J Med Genet 2008; 146: 2871

26. Swollen Optic Disc
• Swelling preferred over edema
– Result of axonal distension
• Most common causes
– Papilledema = optic disc
swelling, no vision loss
– Optic neuritis = optic disc
swelling, acute visual loss
Friedman, Deborah I. "Medication-induced intracranial hypertension in
dermatology." American Journal of Clinical Dermatology, vol. 6, no. 1,
2005, p. 29+. Academic OneFile, Accessed 23 Apr. 2018

27. • Clinical
– Bilateral
– Unilateral papilledema rare in
children
• Optic neuritis, ONG, infiltration
• Symptoms related to increase ICP
– Headache
– Pulsatile tinnitus
– Diplopia on lateral gaze (incomplete)
T2
T1
T2 FLAIR w/
Optic Disc Swelling - Papilledema

28. Intracranial Hypertension
• Younger children present differently
– apathy or lethargy
– HAs continuous
• Types
– Primary (no cause)
– Secondary
• Tumors
• DST
• systemic disease (malnutrition)
• Infectious or Post-infectious
• Withdrawal or ingestion (steroid, vitamin A)

29. Primary
• Imaging
– Secondary evidence of
increased ICP
• Flattening of posterior sclera,
papilledema
• Empty sella
• Enhancement of pre-laminar ON
• Low position of tonsils
– MRI with contrast – evaluate
for CNS disease
17 y/o with HA and increased ICP

30. Imaging
• MRV with contrast
– Venous stenosis
• Result of increased ICP
• Causative, TS stenosis
5 y/o with HA, papilledema
Before
After

31. Secondary
causes
• CNS
– Dural sinus thrombosis
– Meningitis
– AVM
• Systemic
– Malnutrition
– Anemia
– Addison Disease
– Hyperthyroidism
– Down syndrome
17 y/o with pain and minor trauma, papilledema

32. 18 month old with macrocephaly, unknown cause

33. Additional Causes of Optic Disc Swelling
7 y/o with SZ, papilledema
• PRES
• Syndromic craniosynostosis
• Leukemia
– CNS involvement
– Direct infiltration ocular
tissues
• Anterior segment infiltration
without CNS involvement

34. Optic Disc Swelling – Optic Neuritis
• Children are different
– Commonly bilateral
– More commonly associated with disc swelling
– Confused with papilledema
• Clinical distinction from papilledema
– Decreased vision
– Anterior vitreous cells

35. Optic Neuritis
• Infectious
• Para-infectious optic neuritis
– ADEM
• Multiple Sclerosis
– 1/3 present with optic neuritis
17 y/o with acute eye pain and
decreased vision, Bartonella
8 y/o vision loss, HA, papilledema

36. Optic Neuritis
• AQP4 (aquaporin-4) =
Neuromyelitis optica
– Unilateral or Bilateral ON
– Myelopathy
• MRI
– Brain
• Periependymal 3rd and 4th
ventricle, aqueduct
• Thalamus, hypothalamus
• Cloudlike enhancement
– Cord
• Central gray, long segment
Narnett Y, et al. Conventional and Advanced Imaging in Neuromyelitis Optica. AJNR 2014
Chee CG, et al. MRI Features of Aquaporin-4 Antibody–Positive Longitudinally
Extensive Transverse Myelitis: Insights into the Diagnosis of Neuromyelitis
Optica Spectrum Disorders. AJNR 2018
7 y/o with AMS, decreased visual acuity

37. Buphthalmos – Enlarged Globe
• Due to increased intraocular pressure
• Obstruction canal of Schlemm
– Responsible for absorption of aqueous humor
• Less rigid sclera in children

38. • 2 questions
– Generalized or focal?
– Mass or no mass?
• Calcification?
• DDX generalized enlargement
without mass
• Staphloma and severe axial myopia
– Defect temporal to optic disc
• Phakomatoses, collagen vascular
3 y/o with severe myopia 4 year old with esotropia and cortical blindness
18 m/o
Buphthalmos

39. • Ophthalmologic findings
– Choroidal hamartomas
– Lisch nodules
– Optic disc swelling (ONG)
• Buphthalmos
• Increased ocular pressure
(anterior chamber angle)
• Regional overgrowth
6 m/o old with facial asymmetry
Neurofibromatosis type 1

40. Other causes
• Sturge-Weber syndrome
• Clinical
– Seizures, developmental delay
– Homonymous hemianopia
• Buphthalmos
• Obstruction
• Elevated venous pressures

41. Nystagmus
• Infantile
• No need for imaging in neurologically normal child
• When imaging
– Optic pathway and cerebellum

42. Spasmus Nutans
• Clinical
– Nystagmus, head nodding,
torticollis
– Onset 6 months to 1 year
• Possible predictors of chiasmal
glioma
– Optic disc swelling, weight loss
– Large head, Café au lait spots
• Uniform screening likely not
indicated
• 2/40 cases ONH
• No glioma
18 m/o with spasmus nutans

43. Vertical Nystagmus
• Onset <3 months
– Neuroimaging not generally
indicated
• Later onset = posterior fossa
lesion
• Upbeating nystagmus in infancy
– Anterior visual pathway disease
– ERG normal then image for ONG
10 m/o with nystagmus

44. Vertical Nystagmus
• Acquired downbeat
– Dysfunction at level
of the flocculus
– Chiari I
2 y/o with nystagmus

45. Seesaw
Nystagmus
• Congenital
– Achiasma
– Joubert
2 m/o with nystagmus
9 y/o with long standing nystagmus

46. Seesaw Nystagmus
• Acquired
– Craniopharyngioma
– Chiasmatic glioma
6 y/o with HA and nystagmus

47. Neurologic Nystagmus
• Spasmus nutans
• Monocular
• Seesaw
• Convergence retraction (dorsal
midbrain compression)
• Etiologies
– Leigh disease
– Pelizaeus-Merzbacher disease
– Glycosylation disorders
– Infantile neuroaxonal dystrophy
– Ceroid lipofuscinosis
– Maple syrup urine disease Term newborn with nystagmus,
Courtesy Laura Hayes

48. Summary Case
5 m/o with IO tumor by u/s
13q deletion with associated congenital malformations
Mitter D, et al. Genotype–phenotype correlations in patients with
retinoblastoma and interstitial 13q deletions. Eur J Hum Genet 2011; 19: 947

49. Thank you!!
“Look at the orbit on your brain studies
and the brain on your orbit studies.”
tim.booth@childrens.com