Transcript Tuberous Sclerosis Complex

Tuberous Sclerosis Complex
and Seizures
“Knowledge is Power”
STEPHEN J. THOMPSON, MD
CHIEF, PEDIATRIC NEUROLOGY
DIRECTOR, PEDIATRIC NEURO-ONCOLOGY
HACKENSACK UNIVERSITY MEDICAL
CENTER
What is TCS?
 Neurocutaneous disorder
 Neurologic structures and skin are derived from the same
tissue in the embryo
 TSC:
 Bourneville’s Bisease
 Skin, brain, kidneys, heart…
How and Why?
 TCS1 (9q24) and TSC2 (16p13)
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TSC1
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TSC2
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Hamartin
Tuberin
mTOR
 Involves abnormal cellular differentiation, proliferation,
and migration
 Can affect every organ system in the body
 1 of 10,000
TSC Diagnostic Criteria-1
 1998 Consensus Conference
 Major and Minor Criteria
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A combination of findings is required
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No one finding can make the diagnosis
TSC Diagnostic Criteria-2
 Definite TSC:
 Either 2 major features or 1 major feature with 2 minor
features
 Probable TSC:
 One major feature and one minor feature
 Possible TSC:
 Either 1 major feature or 2 or more minor features
TSC: Major Features
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Facial angiofibromas or forehead plaque
Non-traumatic ungual or periungual fibroma
Hypomelanotic macules (more than three)
Shagreen patch (connective tissue nevus)
Multiple retinal nodular hamartomas
Cortical tuber
Subependymal nodule
Subependymal giant cell astrocytoma
Cardiac rhabdomyoma, single or multiple
Lymphangiomyomatosis
Renal angiomyolipoma
TSC Minor Features
 Multiple randomly distributed pits in dental enamel
 Hamartomatous rectal polyps
 Bone cysts
 Cerebral white matter migration lines
 Gingival fibromas
 Non-renal hamartoma
 Retinal achromic patch
 "Confetti" skin lesions
 Multiple renal cysts
TSC Clinical Issues
 Skin
 Heart
 Kidneys
 Lungs, and teeth
 Brain and eyes:
 Seizures
 Cognitive/Academic/Developmental issues
 Subependymal nodules
 SEGA
 Headaches/Hydrocephalus
Seizures in TSC
 Age related
 Infantile spasms
 Lennox-Gastaut Syndrome
 Partial complex seizures
 Generalized seizures.
Infantile Spasms
 1 in 2000 children overall but as many as 40% of
children with TSC
 Specific clinical presentation
 Specific EEG findings
 Treatment:
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ACTH, oral corticosteroids
Zonegran, Topamax
TSC
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Vigabatrin
Other Seizures in TSC
 Partial complex seizures
 Trileptal, Vimpa,t etc…
 Generalized Seizures
 Keppra, Dilantin, Depakote, etc…
 Novel therapy
 Ketogenic Diet
Tumors in TSC: SEGA
 SEGA
 Subependymal giant cell astrocytoma
 Location
 Foramen of Monroe
 Presentation:
 Headaches
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Hydrocephalus
SEGA
 Treatment
 Surgical resection
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Chemotherapy
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Novel agent, AFINITOR (everolimus)
 mTOR inhibitor
 mTOR is inactivated in TSC
 AFINITOR can treat:
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SEGA
AML
Adenoma sebaceum
Seizures?
Resources
 Tuberous Sclerosis Alliance
 www.tsalliance.org
 TS Center at NEREG/HUMC