IMAGING OF NEUROCUTANEOUS

SYNDROME

PRESENTATION BY- CHARUSMITA CHAUDHARY

Moderators: Prof. (HOD) R .K. GOGOI

INTRODUCTION

INTRODUCTION

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

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

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 gliomasA distinctive bony lesion Dysplasia of the sphenoid bone

,Dysplasia or thinning of long bone cortex

First degree relative with NF1

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

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

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”

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

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

ABSENCE OF SPHENOID WINGS

KYPHOSIS & ENLARGEMENT OF NEURAL FORAMINA

HYPERTROPHIED & TWISTED RIBBON RIBS

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.

CASE 1: Cranio-orbital-temporal Neurofibromatosis (Plexiform neurofibroma of ophthalmic division of trigeminal nerve)

Fig 2a T1WI Fig 2d T1WI-GDFig 2b T2WI

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 lesser wing, together giving the typical ‘Bare orbit sign’ (fig 2e)

Fig 2c T2WI

Fig 2e Fig 2f

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.

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 3a T2FS sagittal Fig 3b T2FS sagittal Fig 3c T2 Coronal

Fig 3d T2 coronal

MR TOF Angiography images reveal:- # 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 3bFig 3a Fig 3c

Fig 3d

Fig 3e

Fig 3f

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.

Biopsy.

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 .

Carotid an giography done at Apollo hospital Delhi excluded a tumor of carotid wall

NF-1 : MR Signal Abnormalities - Globus pallidus T2W bright foci w/o mass, don’t enhance - Cerebellar peduncles, pons, midbrain - Globus pallidus , thalamus , optic

radiationsWhat in the heck are they?? - intracellular proteinous fluid?-Dysmyelination ??T1W bright foci

Neurofibromatosis 2

NF2 also has an AD pattern,1 in 50000 Multiple cranial nerve schwannomas are the

hallmark MC in vestibulocochlear nerve

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

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

M.I.S.M.E.M MULTIPLEI INHERITED S SCHWANNOMAM MENINGIOMAE EPENDYMOMA

ENCEPHALOTRIGEMINAL ANGIOMATOSIS

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)

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

STURGE- WEBER SYNDROME :Port wine stain ( PWS) Facial neveus flammeus Blanches with pressure Trigeminal dermatomeV1-opthlmicV2- maxilaryV3-mandibular

PIAL ANGIOMATOSIS,MEDULLARY COLL & CEREBRAL ATROPHY

Case II5 yr female Complaints of focal seizure

involving right side of body ,impaired milestone , right sided weakness

Clinically- portwine strain + , Buphthalmus left

MR imaging…..

Gyriform (linear, convoluted, or serpentine) calcifications

infarction, glioma, purulent meningitis,leukemia (following intrathecal

administration of methotrexateand skull irradiation), ossifying meningoencephalopathy,

and subarachoid fat

Dyke-Davidoff-Masson syndrome

 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 displacementIn some sources it is equated to hemispheric infarction, whereas in other sources any cause ofcerebral hemiatrophy are included.   EtymologyInitially described by C.G Dyke , L.M Davidoff and C.B Masson in 1933 5

Differential diagnosisGeneral considerations includehemimegalencephaly :Sturge-Weber syndrome : can also be an associationRasmussen encephalitis : tends not to have calvarial changes

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

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.

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

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

Pringle’s disease

Subungal fibroma

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

Subependymal Nodules

represent hamartomatous change. seen in 98%

calcification detected in CT (88%) hyperintense on T1WI Iso- to hyp0intense on T2WI

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

White Matter Abnormalities

Superficial white matter abnormalities associated with cortical tubers,

Radial white matter bands (15%–27%)

Cystlike white matter lesions(15%–44%)

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.

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

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.

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

Retroperitoneal LAM

thick- or thin-walled cystic lesions. may reflect dilatation of lymph vessels due to

obstruction

SKELETAL INVOLVEMENT

Cyst like lesions, hyperostosis of the inner

table of the calvaria , osteoblastic changes, periosteal new bone

formation, and scoliosis.

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

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 %.

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)

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.

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

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

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

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

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

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

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

Hypointense WM foci on T1- and T2-WI

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.

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. 

Gorlin syndromeDiagnostic criteriaA 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 20odontogenic keratocysts (see case 1)palmar pits : 3 or morebilamellar calcification of the falx cerebri rib anomalies : bifid rib fused, splayed first degree relative with Gorlin syndromeMinor criteriamacrocephaly frontal bossing, cleft lip or hypertelorismSprengel deformity,  pectus excavatum or pectus carinatum, syndactylybridging of the sella turcica, hemivertebrae, flame shaped radiolucenciesovarian fibroma, medulloblastoma

Gorlin syndrome

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.

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