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American Society of Neuroimaging35th Annual Meeting

Neurocutaneous Disorders and

Posterior Fossa Developmental Anomalies

Jennifer Williams McVige, MDPediatric and Adult Headache and Neuroimaging

General Pediatric NeurologyDent Neurologic Institute

Amherst, NY January 2011

American Society of Neuroimaging35th Annual Meeting

DISCLOSURES

I have no disclosures. My family and I have no investments in nor do I speak for any company or agency.

American Society of Neuroimaging35th Annual Meeting

Pediatric Neuroimaging

Part INeurocutaneous Disorders

Part IIPosterior Fossa Developmental Anomalies

Note: Extra slides are added to the powerpoint for study purposes that will not be presented at the meeting, due to time constraints.

American Society of Neuroimaging35th Annual Meeting

Neurocutaneous Disorders1. Neurofibromatosis Type I and II

2. Tuberous Sclerosis

3. Sturge-Weber Syndrome

4. Von Hippel-Lindau Disease

5. Others (not presented)– Ataxia Telangectasia, Linear Sebaceous Nevi, Hypomelanosis of Ito, Incontinentia Pigmenti, Klippel-Trenaunay-Weber, Osler Weber Rendu, PHACES

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Neurofibromatosis Type I –“Von Recklinghausen”

• Autosomal dominant • NFI gene 17q11.2• Neurofibromin protein impaired• MC neurocutaneous syndrome• Cafe-au-lait spots: 6 or more, 5 mm in

prepubertal and 15 mm in adult• MC associated tumor = optic nerve glioma 1/3• Assoc ADHD and LD• Diff Dx- Schwannomatosis, Demyelination,

Gliomatosis cerebri

Neurofibromatosis Type IDiagnostic Criteria: (need 2 of 7)1. Axillary/Inguinal freckling2. Bone deformities: sphenoid dysplasia,

thinning of long bones3. Café au lait spots4. 1st Degree relative5. Eye findings: Lisch nodules (> or = 2)6. Fibromas (> or = 2 neurofibroma or 1

plexiform neurofibroma)7. Glioma of optic nerve

Axillary Freckles: Multiple Hyperpimented areas 2‐3 mm in diameter

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Café au Lait spots:Almost 100%, HallmarkTrunk and extremities

Distinctive Osseous Lesions: Sphenoid Dysplasia (1‐7%).(images ‐ Neuroradiology on the Net website)

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Lisch Nodules:Dx with slit lamp‐ Hamartomas within the iris.>74% patients with NF‐IPrevalence increases with Age

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Neurofibromas: Small, rubbery, purplish skinSkin, peripheral nerves, GI tract

NF‐1

Plexiform Neurofibroma

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Optic Glioma

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Optic glioma

MR Signal Abnormalities

• T1W Bright Foci– globus pallidus• T2W Bright Foci– w/o mass, don't enhance– Cerebellar peduncles, Pons, midbrain, globus

pallidus, thalamus, optic radiations- Plexiform bright•What are they?? UBOs– Ectopic Schwann cells, Melanocytes ??– Dysmyelination ??– Intracellular proteinaceous fluid ?

May become Neoplasms? (uncommon)

About 60% of the patients in childhood and adolescence show large signal intense zones in the T2-weighted sequence (otherwise known as undetermined bright objects, UBO). These often are mistaken for astrocytomas. Their true nature is not known.

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Neurofibromatosis Type II•Autosomal Dominant•Chromosome 22q1.11•Merlin protein impaired•Progressive deafness, fewer lesionsDx: Bilateral acoustic neuromas

ORParent, sibling or child with NF-II and unilateraleighth nerve mass

ORNeurofibroma, meningioma, glioma, schwannoma orjuvenile posterior subcapsular lenticular opacities.

Neurofibromatosis Type-2M.I.S.M.E.

• Multiple• Inherited• Schwannomas• Meningiomas• Ependymomas

Other CNS tumors - meningioma, spinal cord ependymoma, other cranial and spinal schwannomas

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• Bilateral acoustic neuromas

Bilateral acoustic neuromas T1 iso/hypo, enhance with contrast

• Meningiomas – olfactory groove and multiple• T1 iso/hypo, contrast may enhance, may be en plaque

Multiple Schwanommas and Meningiomas

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Tuberous SclerosisCharacterized by a triad:

1.) Adenoma sebaceum (by age )2.) Epilepsy3.) Mental retardation

Genes (Autosomal Dominant)TSC-1 Harmatin ch 9q34TSC-2 Tuberin ch 16p13.3

• Seizures in infancy, responds to Vigabitrin

Diagnostic criteria for TS

• Definite TSC: Either 2 major or 1 major with 2 minor

• Probable TSC: 1 major and 1 minor • Possible TSC: Either 1 major or 2 minor

Diagnostic criteria for TS• Major Features:

facial angiofibroma or forehead plaqueungual or periungual fibromahypomelanotic macules (>3)shagreen patch (lumbosacral)multiple retinal nodular hamartomascortical tuber (thick cortex, larger gyri) 70-95%subependymal nodule (lateral ventricles, Ca++) 98%subependymal giant cell astrocytoma (SEGA) 15%cardiac rhabdomyomalymphangiomyomatosisrenal angiomyolipoma

Diagnostic criteria for TS

• Minor Features:multiple pits in dental enamelharmartomatous rectal polypsbone cystscerebral white matter radial migration linesgingival fibromasnon-renal harmatomaretinal achromic patchconfetti skin lesionsmultiple renal cysts

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Adenoma Sebaceum

• NOT present at birth• Develop before puberty• Nasolabial fold -> bi-malar• Papules of angiofibroma

Depigmentation• Ash-Leaf Spots

– (Lance-Ovate Shape)• Confetti- Like Hypopigmentation

– (Inverse Freckles)

Subungual fibroma

Tuberous Sclerosis Imaging• Best clue- 98% calcified subependymal nodules

(GRE/SWI) and enhance. If at Foramen of Monroe and enlarging think SEGA.

• Ventriulomegaly• Radial lines – streaky on FLAIR• Focal lacune like cysts WM (vascular)

Diff Dx: X-linked sudpendymal heterotopia, TORCHS, Taylors dysplasia

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Tuberous Sclerosis

T1W contrastT1W non-contrast

Tuberous Sclerosis

TS

T1W w/o and w contrast

Sturge-Weber Syndrome“Encephalotrigeminal angiomatosis”

• Sporadic inheritence• 1.) Facial port wine stain

Trigeminal opthalmic V1 and maxillary V2 2.) Leptomeningeal angioma – ipsilateral in

occipital area usually (80% unilateral)

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Sturge-Weber Syndrome (SWS)

• Other clinical:Glaucoma – BuphthalmosContralateral hemiparesisSeizuresIQ impairedHemianopiamigraine headaches

Sturge-Weber Syndrome (SWS)• Imaging:

CT= Gyral calcificationsxray= trolley track/tram track calcifications

occipital or parietal-occipitalMRI = hemiatrophy, serpentine leptomenigeal

enhancement with pial angiomatosis-with later atrophy and Ca++, enlarged ipsilat choroid plexus, calavarial thickening, gyral enhancement and prominent deep veins.

MRA = High flow AVMsMRV = sinovenous occlusion

Port-Wine Stain (facial nevus)Affects ophthalmic (V1), maxillary (V2), and mandibular (V3) divisions of the trigeminal nerve

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Sturge‐Weber Sturge‐Weber‐ Hemiatrophy

American Society of Neuroimaging35th Annual Meeting

Pediatric Neuroimaging Part INeurocutaneous Disorders

Part IIPosterior Fossa Developmental Anomalies

Note: Extra slides are added to the powerpoint for study purposes that will not be presented at the meeting, due to time constraints.

Posterior Fossa Developmental Anomalies

• 1.) Cerebellar hypoplasia• 2.) Dandy Walker• 3.) Chiari Malformation I-III• 4.) Molar Tooth Malformations

(Joubert)

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Embryology• Stage 1: Dorsal Induction: Formation and closure

of the neural tube. (Weeks 3-4)

• Stage 2: Ventral Induction: Formation of the brain segments and face. (Weeks 5-10)

• Stage 3: Migration and Histogenesis: (Months 2-5)

• Stage 4: Myelination: (5-15 months; matures by 3 years)

Three vesicles Five vesicles

Cerebellar Hypoplasia

• Inherited or aquired by arrested embryogenesis or inc apoptosis

• Difficult to discern etiology. • Small cerebellar hemishperes and vermis• Recommend serial imaging to determine

type. • Renal, cardiac and optho finding can help

diff dx.

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Cerebellar Hypoplasia• Diff Dx:

1.) Isolated Cerebellar Hypoplasia-Nonprogressive congenital atxia, hypotonia, tremor, nystagmus, cognitive speech delays.

2.) Pontocerebellar hypoplasia-ProgressivePCH type 1: profound muscle weakness (SMA)PCH type 2: feeding issues, psychomotor delay, dyskinesiasCongenital D/o of Glycosylation: MR, parkinsonism, ataxia, fat depositionPEHO: progressive encephalopathy, hypsarrhythmia, optic atrophy

• Also can be caused by acquired insults, infections, etc.

Cerebellar Hypoplasia

Barkovich 2010

Dandy Walker Malformation Spectrum

• Many sporadic, some x-linked• Defective development of the roof of the 4th

ventricle with hindbrain developmental arrest. Ventral induction problem.

• Enlarged posterior fossa with upward displacement of the torcular, transverse sinuses, tentorium.

• Cystic dilatation of the 4th ventricle• Varying vermian, cerebellar hypoplasia.• Presence of fastigium/vermian lobulation= better

outcome• VP shunt if hydrocephalus

Dandy Walker

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Dandy Walker Dandy Walker “Variant”

• Milder form• Variable hypoplasia

of inferior vermis without fastigial recess.

• Normal sized posterior fossa (No torcular inversion).

Molar Tooth Malformations“Joubert”

• “Molar tooth” appearance of midbrain on axial images. Thick superior cerebellar peduncles.

• 4th ventricle situated high at midbrain-pons junction.

• Small dysplastic vermis. • Associated with severe hypotonia, ataxia,

oculomotor apraxia, developmental delay, retinal anomalies, seizures, apnea, large head and forehead.

• Multiple types of gene mutatiuons.

Chiari I Malformation•Failure of dorsal induction

•Inferior herniation of a cerebellar tonsil through the foramen magnum with small 4th ventricle

•Types: I : asymptomatic II : brain stem compression (pointed)III : syrinx

Radiopedia.org Chiari I

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Chiari I Malformation•Cervical cord syrinx 20 - 75% •Hydrocephalus 30%•Some cases thought to result from abnormal CSF flow dynamics.•Skeletal anomalies in 23 - 45% platybasia / basilar invagination , atlanto-occipital assimilation , Sprengel deformity•Syndromic associations

Crouzon syndrome ,Hajdu-Cheney syndromeKlippel-Feil syndrome

Radiopedia.org Chiari I

Chiari I MalformationLine joining the basion to the opisthiondefines lower limit of the posterior cranial fossa = reference point for tonsillar ectopia.

above foramen magnum: normal < 3 mm: also normal but the term benign tonsillar ectopia can be used 3 to 6 mm : indeterminate, and needs to be corellated with symptoms and presence of syrnix etc...>6mm : Chiari 1 malformation

above foramen magnum: normal < 5 mm: also normal but the term benign tonsillar ectopia can be used> 5 mm : Chiari 1 malformation

Chiari I Malformation Chiari I Malformation

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Chiari II Malformation

• 100% assoc with neural tube closure defect, usually lumbar myelomenigiocele.

• Cervicomedullary kinking

Chiari III Malformation

• Cervical occipital encephalocele + Chiari II• +/‐ hydrocephalus

Chiari IV• Severe cerebellar

hypoplasia• Small brain stem.• Large posterior

fossa CSF spaces.

Molar Tooth MalformationsJoubert

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References• Barkovich, Moore, Joneset al. Pediatric Neuroimaging, 2010, Amirsys publishing

• Osburn, Blaser, Salzman et al. Diagnostic Imaging Brain, 2004, Amirsys publishing

• Images were courtesy of DENT Neurologic Institute, Dr Laszlo Mechtler, Dr Ronald Alberico, Women’s and Children’s Hospital of Buffalo, Barkovich and Osburn texts and on line images from google images various sources. 

Thank you 

Questions??