Phakomatoses

Question 1

Phakomatoses are characterized by:

Answer 1

• Hamartomas and Congenital Malformations affecting structures of ectodermal origin (visceral organs to a lesser extent)
  
  • Ectodermal Origin:
    
    • Nervous system
    • Skin
    • Globe
    • Retina

Question 2

What are 6 Inherited Cancer Predisposition Syndromes in which exposure to ionizing radiation should be minimized?

Answer 2

• Ataxia-telangiectasia
• Hereditary retinoblastoma
• Li Fraumeni syndrome
• Neurofibromatosis type 1
• Nevoid basal cell nevus syndrome
• Nijmegen breakage syndrome

Question 3

NF1 gene is what?

Answer 3

Tumor supressor gene expressed in neurons, schwann cells, oligodendrocytes

Question 4

Of patients with NF1 - will most develop OPGs?

Answer 4

No, only 15%

Question 5

Of patients with OPGs, do most have NF1?

Answer 5

No, 40%

Question 6

Is unilateral or bilateral involvement of an OPG classic for NF1?

Answer 6

Bilateral

Question 7

What does FASI stand for? How is it defined?

Answer 7

• Focal Area of Signal Intensity - caused by Myelin Vacuolization (layers of myelin become separated as they spiral around the axon)
  
  • No mass effect,
  • No contrast enhancement
  • No hemorrhage
  • Increased diffusivity on DWI

Question 8

What is this? Where are they usually found?

Answer 8

• FASI (in NF1) - Focal Area of Signal Intensity
• Found in globus pallidus, Internal Capsule, Corona radiata, Thalami, Deep cerebellar nuclei.
• NOT found in subcortical white matter/centrum semiovale

Question 9

True or false: OGPs in NF1 are more likely to include primary involvement of the optic nerve (vs only the chiasm and optic radiations)

Answer 9

True - sporadic cases of OPG are more likely to involve only the chiasm/radiations and have a worse prognosis vs. indolent course of NF1 OPGs involving only optic nerve

Question 10

Which course of OPG is more indolent: NF1 or sporadic?

Answer 10

NF1 (worse prognosis if sporadic)

Question 11

What is the treatment for OPG in patients with NF1?

Answer 11

OPGs are low histological grade (pilocytic astrocytomas). They may even regress in patients with NF1. So - treatment should not be aggressive - wait to see if symptomatic/radiologic progression

Question 12

How to differnetiate OPG from FASI?

Answer 12

OPGs have contiguity, mass effect, low T1 on post-contrast, enhancement after contrast, elevations in choline on MRS

Question 13

What is an appropriate protocol for assessment of the Orbits in NF1?

Answer 13

Hi-res (<3mm) T1 and T2 FS axial/coronal sequences through globes, optic nerves, chiasm, followed by T1 FS - post Gad axial/coronal images. Followed by routine brain.

Question 14

Where can an OPG extend when beyond the optic pathway?

Answer 14

• superiorly: into hypothalamus, fornices, septum pellucidum
• Laterally: Temporal lobes
• Posteriorly: Optic radiations
• Inferiorly: into crebral peduncles/brain stem.

Question 15

Is this spectroscopy from a FASI or OPG?

Answer 15

OPG (increased choline to creatine ratio)

Question 16

Gliomas in NF1 other than OPG: What can occur?

Answer 16

Basically - any other low or high grade neoplasm, but typically lower grade, ie pilocytic astrocytomas - which can occur almost anywhere - cerebral hemispheres - brainstem (midbrain and medulla are most common) - These tumors are more indolent than in the general population - can usually be watched. Sometimes no treatment until symptomatic progression.

Question 17

What is this in a patient with NF1?

Answer 17

An area of FASI that turned into a pilocytic astrocytoma (this is why they need to be followed)

Question 18

What is this in a patient with NF1?

Answer 18

• Pilocytic Astrocytoma (FASI would not enhance or have mass effect)
• Tumor course is more indolent than in general population - can usually be followed with no tx unless clinically symptomatic
• Image is of MRS of lesion - Cho/Cr is abnormally high (normal less than 1.5)
• Naa:Cr is abnormally low (normally greater than 2)

Question 19

What is this in a patient with NF1?

Answer 19

Hypothalamic Hamartoma

• Should not be confused with a glioma
• Follows gray matter on all sequences; No enhancement
• With NF1, no association with gelastic seizures or precocious puberty (typically)

Question 20

Why might a patient with NF1 develop hydrocephalus?

Answer 20

Usually from a tectal glioma causing mass effect on the aqueduct

Question 21

What is the typical progression of FASIs?

Answer 21

Lesions appear during late infancy, with a peak of new lesions b/w 6-12 years old. Lesions then regress and are almost never seen after 20 years old.

Question 22

Why do FASIs regress?

Answer 22

• Maybe due to remyelination or myelin repair.

Question 23

Is there abnormal diffusivity in all of the white matter in NF1 - even if it looks normal?

Answer 23

Yes - abnormally increased, maybe related to abnormal myelination and subtle myelin vacuolization (one of the genes for correct myelination within the oligodendrocyte cell is embedded within the NF1 gene)

Question 24

When should FASIs be followed if there is concern for tumor? And what would we be looking for?

Answer 24

6 months to a year - Enlargement, Mass effect, Enhancement, Reduced diffusion in solid portion, Increased blood volume, Increased Choline, Decreased Cr and NAA on MRS

Question 25

In NF1, why are areas of FASI like Globus Pallidus and Thalamus sometimes also bright on T1

Answer 25

Thought to represent increased or remyelination (sort of repair after vacuolization) - typically occurs after T2 prolongation first appears and tends to persist after T2 prolongation disappears.

Question 26

In NF1 - is increased T2 signal in the hippocampi worrisome?

Answer 26

No - This is not progressive. Hippocampal volume is normal or increased (as opposed to mesial temporal sclerosis) - is not progressive.

Question 27

What does this person likely have?

Answer 27

NF1 - large CC due to increased myelination (maybe after repair?) or redundancy of fibers after decreased apoptosis?