Study Presented at the XIX Symposium Neuroradiologicum (Bologna 2010)

1. Brain Artery Stenosis in
Neurofibromatosis Type 1 (NF1)

2. In addition to the most frequently encountered
abnormalities such as café au lait spots, nerve
sheath tumors, low grade gliomas, the protein
product of the NF1 gene (neurofibromin)
expressed in endothelial and smooth muscle
cells, could be responsible for a NF1
associated vasculopathy.

3. “ The prevalence of cerebral arteriopathy in children with NF1 is at
least 6% and was associated with young age and optic glioma”
Rea et al. 2009
Neurofibromin product by the NF1 gene is an ubiquitary protein,
that interacts with RAS
“Nf1 regulation of RAS plays a critical role in vascular smooth muscle
proliferation” *
Xu et al.
*Circulation. 2007 Nov 6;116(19):2148-56. Epub 2007 Oct 22.NF1 regulates a Ras-
dependent vascular smooth muscle proliferative injury response.Xu J, Ismat FA, Wang T,
Yang J, Epstein JA.

4. NF1
Ras
GTP
Ras GDP
Raf
Gef
MEK
ERK
CREB
P P
RSK
NF1
Ras
GTP
Ras GDP
Raf
Gef
MEK
ERK
CREB
P P
RSK
Ras
GTP
Ras GDP
Raf
Gef
MEK
ERK
CREB
P P
RSK
Regulation by NF1 on RAS pathway
endothelial and
smooth muscle
cells proliferation
NF1 associated
vasculopaty

5. - 81 patients with NF1 (diagnosed according to standard criteria NIH)
- 62 studies performed by using a 1.5 T magnet (Intera Philips)
MRI + MRA: axial SE T1w, axial TSE T2w, axial and
coronal FLAIR T2w, DWI/ADC, coronal STIR, T1w Gd +
(when an orbital, a brain or a spine neoplasm was
suspected ), 3D TOF MRA (for vessel imaging and
stenoses research )
- 19 studies perfomed by using a 0.5 magnet (Vectra GE medical System)
MRI : axial, coronal, sagittal GE T1w, axial SE-PD/T2w.
MRA (2D TOF) was performed in only 2 patients

6. “… the NIH Consensus Developement Conference did not recommend CT
or MRI studies for asyimptomatic patients with NF1…” 1
1
“… perform cranial MRI only in patiens in whom there is a
clinical indication, such a visual or endocrine disturbance,
increasing occipitofrontal circumference, headache suggestive of
intracranial pathology, seizures and follow up of intracranial and
spinal tumors…” 2
2
SYMPTOMS N (%)
NEW NF1 DIAGNOSIS 8 (10%)
HEADACHES 20 (25%)
VISUAL DEFICIENCY 21 (26%)
ORBITOFACIAL MASS 10 (12%)
MACROCEPHALY 5 (6%)
FOLLOW UP OF KNOWN BRAIN TUMOR 4 (5%)
DEVELOPMENT DELAY 10 (12%)
PONTINE SIGNS 1 (1%)
SUSPECT PARAMEDIAN DIENCEPHALIC
SYNDROME
1 (1%)

7. Multiple intracranial arterial stenoses were found in 6
patients (7%):
-3 females, 3 males
-Age range: 4-35 / mean: 14,83
-All patients had no clinical signs of cerebral
vasculopaty
A patient with a large fusiform intracavernous
aneurysm of the left ICA and a second controlateral
smaller aneurysm
Sudden left painful ophthalmoplegia caused by
aneurysm thrombosis
Underwent a Brain Angiography

8. Patient
No.
Gender Age at
Neuroimagin
g
MRI Vascular Findings
1 M 22 Stenosis: left ICA
2 F 35 Stenosis: left MCA; right ACA. Narrowing
left ICA
3 F 10 Stenosis: right ICA, right MCA, right PCA,
and both the ACA’s
4 F 4 Stenosis: left MCA
5 M 12 Stenosis: supraclinoid ICA, right PCA
(Moyamoya)
6 M 19 Stenosis: right PCA
7 F 21 Intracavernous aneurysm of left (++) and
right (+) ICA’s

9. Advanced stenosis of the entire
intracranial tract of the left internal
carotid artery (ICA)
- Gender: M
- Age 22 y
- 0.5 T 2D-TOF MRA

10. Important narrowing of left
carotid siphon
Flow signal of the left MCA and
right ACA was not appreciable
-Gender: F
-Age: 35y
-1.5 T MRI-MRA (TOF 3D)

11. -Gender: F
-Age: 10y
-1.5 T MRI-MRA (TOF 3D)
Previously treated by
radiotherapy consequently to a
right optic nerve glioma.
Cavernous malformation of the
left temporal lobe

12. Advanced stenosis of the entire
tract of the right ICA with
absence of flow signal from the
right MCA, and both the ACA’s
and focal stenosis of the right
PCA

13. “…especially for children with optic gliomas treated
with radiotherapy, whereby about 30% of the cases
experience a progressive vascular pathology… within
the field of irradiation…” Childs Nerv Syst (2004),
20:382-391
Localization of the
stenoses, outside of
the irradiated field for
the right optic nerve,
not excluding a
neurofibromatosis
cause!

14. -Gender: F
-Age: 4y
-1.5 T MRI-MRA (TOF 3D)
Stenosis left MCA and rigth
PCA

15. -Gender: M
-Age: 12 y
-1.5 T MRI-MRA (TOF
3D)/CE-MRI
Complete bilateral disappearing of
the supraclinoid ICA and of the
right PCA, with a lot of secondary
vessels collateralizations, delineating
a typical case of Moyamoya (“puff
of smoke”).

16. -Gender: M
-Age: 19 y
-1.5 T MRI-MRA (TOF 3D)
Stenosis of the right PCA

17. -Gender: M
-Age: 21 y
-Angio-CT
-Angiography
Large fusiform intracavernous
aneurysm of the left ICA
BECAME
SYMPTOMATIC:left
painful
ophthalmoplegia
caused by aneurysm
thrombosis.

18. -Prevalence of cerebral arteriopathy in this study was about 7%
-Real prevalence of cerebral arteriopathy could be understimated
because majority of patients are asymptomatic or don’t undergo an
MRA
-About 30% of patients have a progressive vessel stenosis and
symptoms worsening
- Association with optic glioma has been described  possible BIAS:
Patients with glioma undergo brain MRI

19. To be… or not to be…
Actual guidelines: perform MRI only in patients in whom
there is clinical indication
MRA increase time of an MRI-brain exam by about 12%
(Rea et al. 2009)
NF1 patients who are undergoing
neuroimaging should have MRA for detect
arteriopathy that may be progressive and
asymptomatic

21. Service of Neuroradiology University Federico II Neaples