Childhood CNS manifestations of Neurofibromatosis Type 1
Neurofibromatosis type 1 (NF1) is the most common neurocutaneous syndrome, affecting 1 every 2500-3000 individuals1. In 50% of cases it arises
from an autosomal dominant mode of inheritance from mutation of the tumour suppressor NF1 gene located at chromosome 12,3. In the other half of
cases it can arise from a de-novo mutation4.
The disease has a multi-systematic manifestation affecting the orbits, brain, spine, musculoskeletal system, breast, lung and skin5. Many patients have
a tendency to present in childhood, however, although uncommon, it has also been known to present in adulthood3.
CNS manifestations of NF1 can be roughly divided into three main areas where pathology is seen, which are the intracranial, orbital and spinal
regions.
NF1 can have serious consequences for young patients presented with such a diagnosis. The most common neurological disability seen in children is
cognitive difficulty, which is almost always irreversible and will carry through to the patients adulthood6.
NF1 has also been associated with other significantly debilitating neurological conditions including epilepsy and multiple sclerosis (MS)6.
In this presentation we provide a pictorial review of patients that we have encountered at our regional specialist children’s centre presenting with
neuroimaging manifestations of NF1, and provide overview of the relevant features of each.
References
1. Williams VC, Lucas J, Babcock MA et-al. Neurofibromatosis type 1 revisited. Pediatrics. 2009;123 (1): 124-33
2. Osborn AG, Hedlund GL, Salzman KL. Familial Cancer Predisposition Syndromes In: Osborn's Brain, 2nd ed.,Elsevier,2017: 1241-1277.
3. Fortman BJ, Kuszyk BS, Urban BA, et al. Neurofibromatosis type 1: a diagnostic mimicker at CT. Radiographics. 2001;21:601-612.
4. Albright AL, Adelson PD, Pollack IF. Principles and practice of pediatric neurosurgery. Thieme Medical Pub. (2007) ISBN:1588903958.
5. Barkovich AJ, Koch BL, Moore KR. Neurofibromatosis Type 1, Brain. Diagnostic Imaging: Pediatric Neuroradiology, 2nd ed., Elsevier,2015: I-8;2-5.
6. Ferner RE, Gutmann DH. Neurofibromatosis type 1 (NF1): diagnosis and management. Handb Clin. Neurol. 2013;115:939-55.
7. Hyman SL, Gill DS, Shores EA et-al. T2 hyperintensities in children with neurofibromatosis type 1 and their relationship to cognitive functioning. J. Neurol. Neurosurg. Psychiatr. 2007;78 (10): 1088-91.
8. Louis DN, Ohgaki H, Wiestler OD, Cavenee WK "WHO Classification of Tumours of the Central Nervous System. 4th Edition Revised"
Saminderjit Kular
Sheffield Teaching Hospitals NHS Foundation Trust email: [email protected]
Conclusion
Background
Radiological Findings
Moya Moya, Ischaemia, Infarction
Optic Nerve Gliomas
Focal areas of high signal intensity (FASI)
Plexiform Neurofibromas
Sphenoid Wing Dysplasia Cerebral Astrocytomas & Gangliogliomas
Dural Ectasia & Posterior Vertebral Body Scalloping
Lateral Thoracic Meningoceles
FASI, otherwise known as
neurofibromatosis bright objects
(NBO’s), appear as high T2 and
FLAIR signal abnormalities
(white arrows). They most
commonly appear at the basal
ganglia, thalamus, brainstem and
cerebellum. There is some debate
that the number of these lesions
may correlate with cognitive
deficit, however this remains
controversial7. They do not
demonstrate focal mass effect,
which can be a feature
differentiating these lesions from
a focal tumour.
Optic pathway gliomas (ONG’s) are seen in 15% to 20% of the patients
with NF1 and generally cause visual disturbances. Bilateral optic nerve
gliomas are considered pathognomonic for NF1.
Histologically they resemble WHO grade 1 pilocytic astrocytomas with
variable degrees of cystic change and heterogenous enhancement
patterns. However, high-grade optic pathway gliomas can also occur.
They can affect anywhere along the optic pathway, but are most
commonly found at the optic nerves (red arrows) often with associated
enlargement of the nerve itself. Further associations include
cerebrospinal fluid collections within the optic nerve sheath, kinking or
elongation of the nerve. The other common regions are the
hypothalamus and the optic chiasm (blue arrow).
They often display high central T2 signal and the importantly the
absence of calcification can help to differentiate these entities from an
optic nerve meningioma, which is more commonly seen in NF2.
NF1 associated gliomas are generally low grade
and can occur anywhere in the nervous system,
particularly within the supra- and infra-
tentorium.
Juvenile pilocytic astrocytomas (arrows) are the
most common and the incidence of
astrocytomas are higher than the general
population in NF1 patients5.
Contrast enhancement, progression of lesion
size and mass effect may be helpful in
differentiating gliomas from FASI.
Sphenoid wing dysplasia (green star) is a
characteristic, but not a pathognomic
feature of NF1, yet it is classed as one of
the diagnostic criteria for the condition.
The greater wing of sphenoid specifically
is generally the more commonly affected
site.
Dysplasia of the sphenoid wing is often
associated with plexiform neurofibroma
and together, may cause herniation of
temporal lobes into the orbit.
Lateral thoracic meningoceles are defined as the
herniation of the thecal sac through the neural
foramen (arrow).
They are thought to result from a combination of
dural ectasia and meningeal dysplasia.
Over time the neural foramen is eroded and the
protrusion of thecal sac causes development a
dumbbell-shaped appearence that, akin to
menigiomas’s, is isointense on T1/T2 with
surrounding cerebrospinal fluid signal intensity.
Plexiform neurofibromas are an
uncommon variant of neurofibromas
that involve long nerve segments and
their associated branches.
Although they are generally benign
WHO grade 1 tumours, there is a
significant potential for malignant
transformation, which may occur in
5-10% of larger lesions8.
On T1W MRI, they appear
hypointense whilst on T2W imaging
they are seen as having a hyperintense
rim (red arrow), due to CSF, with a
hypointense central focus (blue
arrow) due to collagenous stroma.
These features together give a typical
‘target sign’ appearance.
Dural ectasia is seen a widening or ballooning of
the thecal sac (red star).
Dural ectasia in NF1 may give rise to posterior
vertebral body scalloping due to a lack of
protection to CSF pressures normally provided by
an intact dura.
Whilst seen in several other conditions including
connective tissue disease, mucopolysaccharidoses
and spinal tumours, posterior scalloping of the
vertebral bodies has a characteristic imaging
appearance and is associated with patients
diagnosed with NF1 (blue star).
Stenosis or occlusion of carotid arteries and major branches (Moya Moya
phenomenon) is the most common vascular dysplasia seen in NF1 (red
arrow).
This may cause cerebral ischaemia as observed on CT/MR angiography
(yellow star) with potential for stroke as seen on diffusion weighted imaging
(DWI) (red arrow).
Numerous cerebral collateral vessels may develop as a
result of the ischaemia.
On catheter angiography/CT angiography with 3D
reformats (blue arrows) this is seen as a characteristic
‘puff of smoke’ appearance, literally translated in
Japanese to ‘moyamoya’.
NF1 is the most common phakomatosis, affecting multiple sites and organ systems. CNS manifestations occur in roughly
10-20% of patients and include regions of myelin vacuolization (‘FASI’s’); multiple tumors including optic nerve
gliomas, cerebral astrocytomas and neurofibromas; bony dysplasia; vascular abnormalities; and dural ectasia.
Understanding the characteristic imaging findings, as well as their clinical significance and expected evolution, is
essential when interpreting neuroimaging studies in this patient population.
Development of
arteriovenous malfor-
mations, vascular
ectasia and cerebral
aneurysms may also be
seen.