1. IMAGING OF
NEUROCUTANEOUS
SYNDROME
Moderators: Prof. (HOD) R .K. GOGOI
PRESENTATION BY-
CHARUSMITA CHAUDHARY

2. INTRODUCTION

3. INTRODUCTION

4. INTRODUCTION
Phakomatoses (or "neurocutaneous syndromes")
are multisystem disorders
inherited or spontaneous mutation
Common ectodermal origin
Advances in molecular biology have been able to
localize the genetic abnormality

7. NEUROFIBROMATOSIS TYPE 1
NF1 is the classic von Recklinghausen or "peripheral"
disease.
AD disorder/Spontaneous mutation
Most common, 1 in 2000 to 3000 live births
Inherited predisposition for the development of
benign peripheral nerve sheath tumors
(neurofibromas) true CNS neoplasms

9. Diagnostic criteria
Two or more of the following:
 Six or more cafe´ au lait spots 0.5 cm or larger in prepubertal
individuals 1.5 cm or larger in postpubertal individuals
one plexiform neurofibromas or 2/more neurofibromas of any
type
Two or more Lisch nodules (benign hamartomas)
Freckling in the axilla or groin
Optic gliomas
A distinctive bony lesion Dysplasia of the sphenoid bone
,Dysplasia or thinning of long bone cortex
First degree relative with NF1

11. Neuroimaging Findings
CNS lesions in 15-20%
brain, spinal cord, dural, orbital, vascular
Hamartomatous and neoplastic lesions
Multifocal T2 hyperintense signal changes in 80% of
patients
Optic nerve(5-15%) and non optic glioma(low grade
astrocytoma)
Plexiform Neurofibromas in the head and neck(1/3rd
of patients)-diagnostic

12. Optic Nerve Gliomas
An important and often diagnostic feature of NF1
Surveillance is important, because up to 80% of
patients with ONGs are asymptomatic
B/L ONGs is considered specific for NF1
Primary findings of ONG include
abnormal optic nerve thickening
beading and elongation
abnormal enhancement

14. Plexiform neurofibroma
cutaneous or subcutaneous neurofibromas
intraorbital and facial br of CN III - VI,
MC affects CN V
Diffuse plexiform neurofibroma of the face and
eyelids,
Sphenoid dysplasia is one of the "distinctive bone
lesions”

15. SKELETAL MANIFESTATIONS :
MOST COMMONLY INVOLVED AREAS-SPINE & SKULL.
1.SPINE:
KYPHOSCOLIOSIS OF LOWER THORACIC SPINE(MOST
COMMON),CERVICAL SPINE.
 POSTERIOR VERTEBRAL BODY SCALLOPING;
 POSTEROCENTRAL DUE TO DURAL ECTASIA.
 ECCENTRIC UNILATERAL DUE TO DUMBBELL
NEUROFIBROMA.
 ENLARGED INTERVERTEBRAL FORAMEN
 PARASPINAL SOFT TISSUE.
DUMBBELL NEUROFIBROMA
INTRATHORACIC meningocele

16.  2.SKULL:
 -AGENESIS OR HYPOPLASIS OF POSTERIOR WALL OF ORBIT,
WINGS OF SPHENOID & ORBITAL PLATE OF FRONTAL.
 -OPTIC FORAMEN ENLARGEMENT
 -GEOGRAPHIC BONE LESION AROUND THE LAMDOID SUTURE
ALONG WITH MASTOID HYPOPLASIA.
 MACROCRANIUM.
 3. RIB:
 - TWISTED RIBBON RIB– THIN IRREGULAR, SCALLOPED
ATTENUATED APPEARANCE OF RIBS.
 4. LONG BONES:
 - PSEUDOARTHOSIS.
 -FOCAL GIGANTISM
 -SUBPERIOSTEAL OR CORTICAL LUCENCIES DUE TO
INTRAOSSEOUS NEUROFIBROMA.
 -CORTICAL PRESSURE RESORPTION DUE TO ADJACENT SOFT
TISSUE

18. ABSENCE OF SPHENOID WINGS

23. KYPHOSIS & ENLARGEMENT OF NEURAL
FORAMINA

27. HYPERTROPHIED & TWISTED RIBBON
RIBS

33. CASE 1: Cranio-orbital-temporal Neurofibromatosis
(Plexiform neurofibroma of ophthalmic division of
trigeminal nerve)
History :-
# 15 year old female patient presented with
a large painless swelling over right eyelid
and face causing cosmetic deformity.
Clinical examination :-
# A large boggy swelling over right upper lid
and temporal regions with a feeling of bag
of worms on palpation. No vascular
pulsation noted.

34. Fig 2b T2WI Fig 2c T2WI Fig 2d T1WI-GD
Fig 2a T1WI
MRI (T1WI) & 3D Volume rendered CT
images reveal –
# Enlargement of the right middle
cranial fossa with herniation of the right
temporal lobe into the posterior aspect
of the right orbit with a preceding
anterior sleeve of CSF (fig 2a)
# Hypoplasia of the greater wing of the
sphenoid bone and superiorly displaced
Fig 2e Fig 2f
lesser wing, together giving the typical
‘Bare orbit sign’ (fig 2e)

35. CASE2: Cutaneous Neurofibroma with Extracranial Arterio-
venous malformation and Atlanto-axial dislocation
# 25 year old male patient presented with vertigo, tinnitus in left ear and a gradually
progressing quadriparesis for 25 days.
# Clinical examination revealed:
1. Multiple subcutaneous nodules with plexiform neurofibroma
2. Decreased power of all the limbs with intact sensations and bilateral extensor plantar jerks
3. Otoscopic examination, audiometry and Laboratory parameters were unremarkable.

36. Fig 3a T2FS sagittal Fig 3b T2FS sagittal Fig 3c T2 Coronal
Sagittal and coronal MR images shows :-
# Atlanto-axial dislocation with retropulsion of odontoid tip
leading to secondary foramen magnum stenosis (fig 3a).
# Dilated, Tortuous V3 segment of left vertebral artery with
formation of multiple blood filled channels. (fig 3c,d).
# Distended venous sac in anterior epidural space displacing
the spinal cord posteriorly and to the right, causing
compressive cord myelopathic changes (Fig 3b,c )
Fig 3d T2 coronal

37. Fig 3d
Fig 3a Fig 3b Fig 3c
MR TOF Angiography images reveal:-
Fig 3e
# Arterio-venous malformation in posterolateral aspect of left
side of neck .
Feeders --- V3 segment of vertebral artery (fig 3a,b) &
an anomalous artery arising from 1st part of left subclavian
artery (fig 3c).
Draining --- left sigmoid sinus (fig 3e) with a hugely distended
venous sac in cervical canal.
Fig 3f

38. Case 3 : Neurofibromas of the vagus nerve of the neck
32-years old female patient .
Gradual onset of swelling , increasing on size on the right
side of the neck for about few months.
Clinical examination :An ill-defined, palpable lobulated
lesion was observed on the left side of the neck. Café au lit
spots were not detected on the skin.

39. Carotid an-giography done at Apollo hospital Delhi
Biopsy.
excluded a tumor of carotid wall
Histological examination showed that the typical
features of neu-rofibromatic tumour -spiral cells
and highly collagenised stroma.
Neurofibromas of the vagus nerve
on the neck are extremely rare .

40. NF-1 : MR Signal Abnormalities
- Globus pallidus
T2W bright foci w/o mass, don’t enhance
- Cerebellar peduncles, pons, midbrain
- Globus pallidus , thalamus , optic radiations
What in the heck are they??
- intracellular proteinous fluid?
-Dysmyelination ??
T1W bright foci

42. Neurofibromatosis 2
NF2 also has an AD pattern,1 in 50000
Multiple cranial nerve schwannomas are the hallmark
MC in vestibulocochlear nerve

43. DIAGNOSTIC CRITERIA FOR
NEUROFIBROMATOSIS 2 (NF2)
Bilateral CP angle masses (histologic proof not
required)
A first-degree relative with NF2 and either
-A unilateral CPA mass or
-Any two of the following:
schwannoma, meningioma, glioma, neurofibroma, or
juvenile posterior subcapsular cataract

44. CNS lesions -100%
Brain - CN VII schwannomas, multiple schwannomas
of other cranial nerves,
Meningiomas,
Spinal cord/roots - Cord ependymomas, multilevel
bulky schwannoma, Meningioma
Spine-Secondary changes
Cutaneous manifestations rare

47. M.I.S.M.E.
M MULTIPLE
I INHERITED
S SCHWANNOMA
M MENINGIOMA
E EPENDYMOMA

51. ENCEPHALOTRIGEMINAL ANGIOMATOSIS

53. DIAGNOSTIC CRITERIA FOR STURGE-WEBER
SYNDROME
Seizures
Mental handicap
Port-wine stain (neveus flammeus)
Leptomeningeal capillary/venous malformation
(ipsilateral to no. 1)
Cerebral hemiatrophy (ipsilateral to no. 1)
Facial hemihypertrophy (ipsilateral to no. 1)
Somatic hemiatrophy (contralateral to no. 1)

54. CT and MR can reveal the secondary
changes,
cerebral cortical atrophy,
gyriform cerebral calcification (tram-track),
compensatory ventricular enlargement,
"angiomatous“ enlargement of the ipsilateral choroid
plexus, and
calvarial hemihypertrophy
MR- direct visualization of the persistent embryologic
plexus in subarachnoid space
Ocular lesions - Buphthalmos, Scleral/choroidal
angiomata

55. STURGE- WEBER SYNDROME :
Port wine stain ( PWS)
Facial neveus flammeus
Blanches with pressure
Trigeminal dermatome
V1-opthlmic
V2- maxilary
V3-mandibular

56. PIAL ANGIOMATOSIS,MEDULLARY COLL
& CEREBRAL ATROPHY

59. Case II
5 yr female
Complaints of focal seizure
involving right side of body
,impaired milestone , right sided
weakness
Clinically- portwine strain + ,
Buphthalmus left
MR imaging…..

62. Gyriform (linear, convoluted, or serpentine)
calcifications
infarction, glioma, purulent meningitis,
leukemia (following intrathecal administration
of methotrexateand skull irradiation), ossifying
meningoencephalopathy,
and subarachoid fat

64. Dyke-Davidoff-Masson syndrome

65. Dyke-Davidoff-Masson syndrome (DDMS) was initially described as
changes in the skull seen on skull X-ray in patients with cerebral
hemiatrophy, but is now applied more broadly to cross-sectional imaging
also. It is characterised by :
•thickening of the skull vault (compensatory)
•enlargement of the frontal sinus (also ethmoidal and mastoid air-cells)
•elevation of the petrous ridge
•ipsilateral falcine displacement
In some sources it is equated to hemispheric infarction, whereas in other
sources any cause ofcerebral hemiatrophy are included.
Etymology
Initially described by C.G Dyke , L.M Davidoff and C.B Masson in
1933 5
Differential diagnosis
General considerations include
hemimegalencephaly :
Sturge-Weber syndrome : can also be an association
Rasmussen encephalitis : tends not to have calvarial changes

68. Tuberous sclerosis
AD; 50% from new spontaneous mutations
1 in 20,000 to 1 in 50,000
nearly 40% of patients die by the age of
35 years
prominent cutaneous, visceral, and CNS
manifestations
Most lesions are hamartomas

69. DIAGNOSTIC CRITERIA FOR TSC
Definite TSC
Two major features, or
one major plus two minor features.
Probable TSC
One major plus one minor feature.
Possible TSC
one major feature, or
two or more minor features.

70. DIAGNOSTIC CRITERIA FOR TSC
MAJOR FEATURES
Hypomelanotic macules (three or more), Shagreen
patch
Facial angiofibromas (adenoma sebaceum) or ungual
or periungual fibromas
Multiple retinal nodular hamartomas,
Cortical tubers, Subependymal nodule,
Subependymal giant cell astrocytoma
Cardiac rhabdomyoma - single or multiple
Lymphangiomyomatosis.
Renal angiomyolipoma

71. DIAGNOSTIC CRITERIA FOR TSC
MINOR FEATURES
Multiple pits in dental enamel
Gingival fibromas
Hamartomatous rectal polyps
Bone cysts
Cerebral white matter radial migration lines
Retinal achromic patch
Multiple renal cysts
Nonrenal hamartoma
"Confetti" skin lesions

73. Pringle’s disease

74. Subungal fibroma

80. Cortical tubers:
considered to be closely related to neurologic
manifestations of TS - epilepsy, cognitive disability,
and neurolobehavioral abnormalities
50% seen in frontal lobe
Hypointense on T1-WI
Hyperintense on T2-WI, FLAIR
Only 10 % enhance

84. Subependymal Nodules
represent hamartomatous change.
seen in 98%
calcification detected in CT (88%)
hyperintense on T1WI
Iso- to hyp0intense on T2WI

86. SGCAs
proliferative astrocytes and giant cells.
1.7%–26% prevalence
Typically in foramen of Monro
Differ from other cerebral astrocytomas in having a
benign biologic and pathologic features (slow growth,
minimal or no attendant brain edema, and minimal
invasiveness)
tend to be larger tumors (>1 cm) with incomplete
calcifn & more intense enhancement
MRS shows high Cho/Cr and low NAA/Cr r

88. White Matter Abnormalities
Superficial white matter abnormalities associated
with cortical tubers,
 Radial white matter bands (15%–27%)
Cystlike white matter lesions(15%–44%)

90. PULMONARY AND THORACIC
INVOLVEMENT
lymphangioleiomyomatosis (LAM)
multifocal micronodular pneumocyte hyperplasia
(MMPH).
approx 1%–2.3% of TS patients.
complications of LAM Pneumothorax and chylous
pleural effusion
ascites.

91. round, thin-walled cysts of variable size and contour At thin-section CT, multiple tiny nodules (1–8 mm
in diameter) are diffusely scattered throughout the
lung in a random distribution

92. RENAL AND RETROPERITONEAL
INVOLVEMENT
Renal angiomyolipoma (AML),
renal cysts, and
RCC
Renal AML in 55%–75% patients with TS
Retroperitoneal LAM in up to 20% of patients with
pulmonary LAM.

93. AMLs
MC benign tumors of the kidney.
characterized by variable amounts of abnormal
vessels, immature smooth-muscle and fat cells
Compared with sporadic lesions, AMLs seen in
patients with TS tend to manifest at a younger age
multiple, larger, and bilateral and
Tend to grow.
noncalcified cortical tumors containing fat of less
than −20 HU

96. Retroperitoneal LAM
thick- or thin-walled cystic lesions.
may reflect dilatation of lymph vessels due to
obstruction

97. SKELETAL INVOLVEMENT
Cyst like lesions,
hyperostosis of the inner
table of the calvaria ,
osteoblastic changes,
periosteal new bone
formation, and
scoliosis.

98. VON HIPPEL-LINDAU DISEASE
AD disorder linked to defect on the short arm of
chromosome 3p.
Prevalence is approximately 1 in 40,000 to 1 in 50,000
people
Causes of death - cerebellar hemangioblastoma and
RCC
Screening is important because the lesions in VHL
disease are treatable

99. Manifestations of VHL Disease according to
Prevalence
Cerebellar hemangioblastoma 44–72%
Medullary hemangioblastoma 5%
Spinal cord hemangioblastoma 13–59%
Retinal hemangioblastoma 45–59%
Renal cell carcinoma 24–45%
Pheochromocytoma 0–60%
Neuroendocrine tumor of the pancreas 5–17%
Serous cystadenoma of the pancreas 12%
Pancreatic cysts 50–91%
Renal cysts 59–63%
Papillary cystadenoma of epididymis 10–60 %.

100. NATIONAL INSTITUTES OF HEALTH CLASSIFICATION
Type I
VHL without pheochromocytoma
most common type
Renal and pancreatic cysts, RCC
Type II
VHL with pheochromocytoma
IIa - Islet cell tumors (no cysts)
Iib - Renal/pancreatic disease (least common)

101. DIAGNOSTIC CRITERIA
More than one CNS hemangioblastoma,
One CNS hemangioblastoma + visceral
manifestations of VHL disease,
Any manifestation and a known family history of VHL
disease.

102. Hemangioblastoma
Hallmark of VHL
Seen in 2/3 of patients
20-50 yrs of age
Typically multiple
MC in cerebellum
Other::::medulla > pons, spinal cord, and
supratentorially in optic N and cerebrum

105. Retinal angiomas
are actually hemangioblastomas (40-50%)
asymptomatic or cause a blind spot.
may hemorrhage and can cause retinal detachment
Higher signal intensity than normal vitreous on non-
enhanced T1WI

106. Renal lesions
Renal cysts in 59%–63%
RCC in 24%–45% either multicentric and bilateral
solid hypervascular masses or complex cystic masses
Complex or solid lesions enhance on postcontrast T1-
WI
A hypointense pseudocapsule on T2-WI

108. Pancreatic involvement
simple pancreatic cysts
(50%–91%)
serous microcystic
adenomas
Pancreatic
neuroendocrine tumors
(5%–17%)
Pancreatic lesions may
be the only abdominal
manifestation and may
precede any other
manifestation by
several years

109. Annual screening examinations of the abdomen, by
ultrasound or CT, have been recommended for some
patients with VHL

110. Ataxia-telangiectasia
AR disorder
1 in 20,000-100,000
Telangiectasias in skin (face) and eyes,
cerebellar ataxia
immunodeficiency syndromes, and recurrent
infections and susceptibility to certain neoplastic
processes

111. MR FINDINGS
Telangiectasia of pia mater and white matter
Hypointense WM foci on T1- and T2-WI
Diffuse symmetric increased T2 white matter signal
Severe cerebellar atrophy

112. Hypointense WM foci on T1- and T2-WI

114. THE PHACE SYNDROME
Posterior fossa malformations
Hemangiomas
Arterial anomalies
Coarctation of the aorta , cardiac defects
Eye abnormalities
 Sometimes, an S is added making it PHACES, with
the S standing for Sternal defects and/or
Supraumbilical raphe.

116. Large facial hemangiomas may be associated with a Dandy-
Walker malformation, vascular anomalies (coarctation of
aorta, aplasia or hypoplastic carotid arteries, aneurysmal
carotid dilation, aberrant left subclavian artery), glaucoma,
cataracts, microphthalmia, optic nerve hypoplasia, and ventral
defects (sternal clefts)
Facial hemangioma is typically ipsilateral to the aortic arch
Female predominance
Patients with large facial cutaneous (S1-S4) hemangiomas
were especially at risk of CNS structural and cerebrovascular
anomalies; S1 with ocular anomalies; and S3 with airway,
ventral, and cardiac anomalies.

118. Gorlin syndrome
 Diagnostic criteria
 A clinical diagnosis can be made using major and minor criteria.
 To make the diagnosis, either two major or, one major and two minor
criteria must be met.
 Major criteria( Classical triad )
 basal cell cancers : > 2 or 1 under the age 20
 odontogenic keratocysts (see case 1)
 palmar pits : 3 or more
 bilamellar calcification of the falx cerebri
 rib anomalies : bifid rib fused, splayed
 first degree relative with Gorlin syndrome
 Minor criteria
 macrocephaly
 frontal bossing, cleft lip or hypertelorism
 Sprengel deformity, pectus excavatum or pectus carinatum, syndactyly
 bridging of the sella turcica, hemivertebrae, flame shaped radiolucencies
 ovarian fibroma, medulloblastoma

119. Gorlin syndrome

120. Conclusion
Phakomatoses are a diverse group of disorders
Most common phakomatoses (excluding SWS) are
AD; therefore, a correct diagnosis has genetic
implications
A screening evaluation of all first-degree relatives to
see if they are also affected is mandatory
A routine follow-up surveillance program should be
established. This typically includes annual CNS
imaging studies and, where appropriate, abdominal
ultrasound, CT, or MR.

121. THANK YOU