Optic Glioma in NF1

Kelly Liesse, MS4

Patient History
22 mo old M with NF1 diagnosed clinically by
presence of >20 caf au lait spots and paternal
hx, confirmed with genetic testing
Met developmental milestones up to 1 year of age
Now presents with increasing head size per
parents, speech delay and wide based gait
Rare R eye deviation per parents
Hx of 1 (possibly febrile?) seizure, seen at OSH

Physical Exam
VITALS: T: 36.3 P: 98 RR: 20 BP: 105/60
Growth: L 47.3%ile, W 22.2%ile, HC 100%ile
Gen: alert, active, NAD, non-verbal
HEENT: macrocephaly, +Lisch nodules,
PERRL, EOM full, no oral/pharyngeal lesions, no
LAD
Resp: CTAB, no increased WOB
CV: RRR, S1 + S2, no murmurs

Physical Exam
Abd: soft, NTND, no organomegaly
Ext: 3 x 4mm subQ firm nodule on lateral
R forearm, full ROM in b/l upper and lower
extremities
Skin: >20 caf au lait spots, no swelling,
masses, pallor or rash
Neuro: motor, sensory and coordination
grossly nl, no ataxia or nystagmus, CN intact,
optic discs nl, wide but steady gait

Pertinent Lab Results

Electrolytes, CBC & LFTs all within normal
limits

Clinical Question and/or

Differential Diagnosis
22 month old M with NF1 presenting with
macrocephaly and developmental delay.
Must consider intracranial tumor (optic or
other CNS gliomas) and hydrocephaly as
potential causes of both macrocephaly
and developmental delay. Also consider
intracranial bleed or megalocephaly.

ACR Appropriateness Criteria

for Imaging Study
Infant/Child with orbital asymmetry,
proptosis and visual loss: MRI head and
orbits w/wo IV contrast
Rating 8 (usually appropriate)
No radiation exposure

Pts with NF1 have a low threshold for Brain

MRI due to associated intracranial tumors

MRI Brain & Orbit w/wo contrast

MRI brain w/wo contrast largely unremarkable
Ventricles normal in size and position without
hydrocephalus
No evidence of intraparenchymal hemorrhage or
abnormal diffusion
Midline structures with normal contours and normal
craniocervical junction
No intra- or extra-axial fluid collection
Patent dural venous sinus

MRI orbit w/wo contrast

Axial T1 precontrast

Coronal T2
pre-contrast

Axial T1
postcontrast

Coronal
T1 postcontrast

R para-sagittal T1 postcontrast

Neurofibromatosis 1
Hereditary AD neuro-cutaneous
disorder affecting 1:2500
Variable expression but 100% penetrance
Mutation of neurofibromin, a tumor suppressor on chr. 17

Clinical Symptoms
Caf au lait spots, axillary/inguinal
freckling, dermal neurofibromas
Lisch nodules (iris hamartomas)
Optic and other CNS gliomas, pheochromocytoma, carcinoid
tumors, plexiform neurofibromas, malignant peripheral nerve
sheath tumors
Bowing of long bone, sphenoid wing dysplasia

OPTIC NERVE GLIOMA

Most common CNS tumor associated with
NF1, with prevalence of 15-20%
Macrocephaly highly associated with optic
nerve glioma in NF1 pts
Excellent prognosis, median survival >15yrs;
5% invade optic chiasm
NF1 patients with 2x recurrence rate
compared to optic glioma not associated with
NF1

OPTIC NERVE GLIOMA

Treatment:
Observation appropriate if exclusively involve
optic nerve (monitor with serial MRI/neuro-ophthalmic exams
q3mo)

Treatment initiated if extension into optic canal or

progressive visual compromise
Chemotherapy 1st line treatment
If proptosis + poor/no vision, consider surgical excision
Avoid radiation tx in children with NF-1 due to
increased risk of secondary malignancy

Imaging in NF-1
Low threshold for MRI due to increased CNS tumor
risks
Focal areas of signal intensity (FASI) often in basal ganglia
or corpus callosum, no contrast-enhancement
Optic nerve glioma screening and serial monitoring
Progressive sphenoid wing dysplasia
Dural calcification

CT and plain films: assessment and serial monitoring

of long bone bowing, cranial bone malformation, limb
overgrowth

References

Hasso, A. N., et al. "Orbits, vision, and visual loss. American College of Radiology.
ACR Appropriateness Criteria." Radiology 215 (2000): 579-587.
Balcer LJ, Liu GT, Heller G, et al. Visual loss in children with neurofibromatosis type 1
and optic pathway gliomas: relation to tumor location by magnetic resonance
imaging. Am J Ophthalmol. 2001;131(4):442-445.
Van Es, S., North, K. N., McHugh, K., & De Silva, M. (1996). MRI findings in children
with neurofibromatosis type 1: a prospective study. Pediatric radiology, 26(7), 478487.
Schindera, Christina, et al. "Macrocephaly in neurofibromatosis type 1: a sign post for
optic pathway gliomas?." Child's Nervous System 27.12 (2011): 2107-2111.
Blanchard, G., Lafforgue, M. P., Lion-Franois, L., Kemlin, I., Rodriguez, D.,
Castelnau, P., ... & Chaix, Y. (2016). Systematic MRI in NF1 children under six years
of age for the diagnosis of optic pathway gliomas. Study and outcome of a French
cohort. European Journal of Paediatric Neurology,20(2), 275-281.
Avery, R. A., Mansoor, A., Idrees, R., Biggs, E., Alsharid, M. A., Packer, R. J., &
Linguraru, M. G. (2016). Quantitative MRI criteria for optic pathway enlargement in
neurofibromatosis type 1. Neurology, 10-1212.