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
5.
6.
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
8.
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
10.
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
13.
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
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
41.
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
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
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…..
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
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
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
87.
88. White Matter Abnormalities
Superficial white matter abnormalities associated
with cortical tubers,
Radial white matter bands (15%–27%)
Cystlike white matter lesions(15%–44%)
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
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
103.
104.
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
107.
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
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
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.
115.
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.
117.
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
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.