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: skular2@doctors.org.uk

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.