NEUROIMAGING OF PHAKOMATOSES IN CHILDREN

1. NEUROIMAGING OF PHAKOMATOSES IN CHILDREN Daniela LONGO daniela.longo@opbg.net Bologna, October 6, 2010

2. What are phakomatoses? • [fak′ōmətō′sis] pl. phakomatoses • Etymology: Gk, phako, lens, oma, tumor, osis, condition (in ophthalmology); any of several hereditary syndromes characterized by benign tumorlike nodules of the eye, skin, and brain. • Congenital malformations affecting mainly structures of ectodermal origin, that is, the nervous system, the skin, and the eyes; visceral organs are also involved, but more rarely. • Some phakomatoses are associated with a higher risk of developing tumors.

3. What are phakomatoses? • Ataxia-Telangectasia (Rendu-Osler-Weber syndrome) • NeurocutaneousMelanosis • IncontinentiaPigmenti • Epidermal Nevus Syndrome • Hypomelanosis of Ito • Basal Cell Nevus Syndrome • CutaneousHemangioma – Vascular Complex Syndrome • Chédiak-Higashi syndrome • Cowden Syndrome • Parry-Romberg syndrome Encephalocraniocutaneouslipomatosis • Neurofibromatosis type 1 (NF1) • Tuberous sclerosis complex (TSC) • Sturge-Weber syndrome (SWS) • Neurofibromatosis type 2 (NF2) • Von Hippel-Lindau disease

4. Neurofibromatosis type 1 (NF1) Von Recklinghausen disease • Multisystemicneurocutaneous disorder • Autosomal dominant, gene NF1 (17q11.2) • Incidence 1/3.000 • Café au lait spots • Axillary and inguinal freckling • Cutaneous or plexiformneurofibromas • Optic nerve and other CNS gliomas • Iris Lisch nodules • Bone lesions (tibial dysplasia and sphenoid dysplasia) • Vasculopathy

5. Neuroradiological Manifestations • UBOs (Unidentified bright objects) • Optic nerve gliomas • Brainstem and hemispheric tumors • Neurofibromas and plexiformneurofibromas • Sphenoid dysplasia

6. abnormal high signal intensity lesions on T2-WI • globuspallidus, thalamus, hypocampus, pons, midbrain, cerebellar white matter • do not enhance after contrast administration, • no mass effect, do not cause edema • generally absent in the first 2 years of life, they increase in number and size up to the age of 10 – 12 years, then they decrease in number and size Unidentified Bright Objects (UBOs) T2 T2 T2 FLAIR

7. The most common primary brain abnormality in NF1 (15%) • Single or both optic nerves, the chiasm , the optic tracts and radiations • Low histologic grade • May spontaneously involute Optic Nerve Gliomas Enlargement of the optic chiasm and hydrocephalus. Bilateral optic nerve gliomas. Axial postcontrast T1W image shows enhancement of both optic nerve tumors.

8. 2 yars-old, seizures Glioblastoma (WHO IV) Astrocytomas and Glioblastomas 7-year-old left eyelid ptosis, strabismus Low-grade astrocytoma (WHO I) Areas of necrosis Astrocytes gemistociti HE 4X HE 20X

9. Sphenoid wing dysplasia is often associated with plexiformneurofibromas in the orbit. • Histologically :Schwann cells, neurons, collagen and intercellular matrix. PlexiformNeurofibromas and Sphenoid Dysplasia • . • Axial CT shows partial absence of the greater wing of the left sphenoid bone. • On MR the soft tissue mass in the left orbit is a plexiformneurofibroma. The postcontrast axial T1W image with fat saturation shows mass enhancement.

10. DIFFERENTIAL DIAGNOSIS • Demyelinating diseases (ADEM, multiple sclerosis) • Viral encephalitis (Epstein-Barr, CMV) • Mitochondrial diseases (PKAN, Leigh, Kearns-Sayre syndrome) • Glutaric-aciduria • Halleworden-Spatz • Krabbe disease • Tuberous sclerosis complex

11. Tuberous Sclerosis Complex (TSC) (Bourneville-Pringle’s disease) • Multisystemic disorder (skin, CNS, bones, respiratory system, kidneys, heart and skeletal muscle) • Autosomal dominant; genes TSC1 (9q) and TSC2 (16p) • Incidence 1/6.000 • facial angiofibromasor forehead plaque • ungual or periungualfibromas • hypomelanoticmacules (three or more) • Shagreen patch (connective tissue nevus) • multiple retinal nodular hamartomas • cardiac rhabdomyoma • lymphangiomyomatosis • renal angiomyolipoma • multiple pits in dental enamel • hamartomatous rectal polyps • bone cysts • gingival fibromas • nonrenalhamartoma • retinal achromic patch • "Confetti" skin lesions • multiple renal cysts Clinical triad : mental retardation, epilepsy, facial angiofibromas

12. Neuroradiological Manifestations • Subependymal nodules (90%) • Cortical tubers (70%) • Giant cell astrocytomas (6%-14%) • White matter radial migration lines

13. Subependymal Nodules and Cortical Tubers Signalchanges in myelination Unmyelinatedwhitematter (infants) Hyperintense on T1WI Hypointense on T2WI Myelinatedwhitematter Isointense on T1WI Hyperintense on T2WI *hypointensity on T2WI /(Ca++)

14. DIFFERENTIAL DIAGNOSIS • Subependymalheterotopia • Cytomegalovirus • Cortical dysplasia

15. Sturge-Weber Syndrome(EncephalotrigeminalAngiomatosis) Congenital disorder characterized by • Angiomatosis of the face, the coroid and leptomeninges • Seizures, hemiparesis, hemianopsia, and mental retardation • Incidence: 1:50.000

16. Neuroradiological Manifestations • Leptomeningealangioma • Hemispheric atrophy • Loss of the white matter • Hypointensity of the white matter below the affected cortex • Gyral calcification • Prominent choroid plexus • Dilated subependymal veins

17. DIFFERENTIAL DIAGNOSIS • Bilateral empyema • Arteriovenous malformations • Neurocutaneous syndromes (PHACES, meningioangiomatosis, “blue rubber bleb nevus”syndrome, Wyburn-Mason syndrome)

18. Ospedale Pediatrico Bambino Gesù - Roma Thankyouforyourattention Daniela Longo daniela.longo@opbg.net

19. Von Hippel-Lindau Disease • Retinal angiomas (70%) • Hemangioblastomas of the brain (50%) and spinal cord • Renal cell carcinoma (40%) • Pheochromocytoma • Endolymphatic sac tumors (10%) • Cysts of the pancreas, kidney, liver and epididymis. • Autosomal dominant, gene VHL (3p25-p26) • Incidence 1:36.000

20. DIFFERENTIAL DIAGNOSIS • Solitary hemangioblastoma • Pilocytic astrocytoma • Hemispheric medulloblastoma • Multiple AVMs in Osler-Weber-Rendu and Wyburn-Mason