1. Tuberous Sclerosis Complex and Seizures “Knowledge is Power”
Stephen J. Thompson, MD
Chief, Pediatric Neurology
Director, Pediatric Neuro-Oncology
Hackensack University Medical Center

2. What is TCS? Neurocutaneous disorder TSC:
Neurologic structures and skin are derived from the same tissue in the embryo
TSC:
Bourneville’s Bisease
Skin, brain, kidneys, heart…

3. How and Why? TCS1 (9q24) and TSC2 (16p13)
Hamartin
TSC2
Tuberin
mTOR
Involves abnormal cellular differentiation, proliferation, and migration
Can affect every organ system in the body
1 of 10,000

4. TSC Diagnostic Criteria-1
1998 Consensus Conference
Major and Minor Criteria
A combination of findings is required
No one finding can make the diagnosis

5. 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

6. TSC: Major Features 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

7. 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

8. TSC Clinical Issues Skin Heart Kidneys Lungs, and teeth
Brain and eyes:
Seizures
Cognitive/Academic/Developmental issues
Subependymal nodules
SEGA
Headaches/Hydrocephalus

9. Seizures in TSC Age related Infantile spasms Lennox-Gastaut Syndrome
Partial complex seizures
Generalized seizures.

10. Infantile Spasms
1 in 2000 children overall but as many as 40% of children with TSC
Specific clinical presentation
Specific EEG findings
Treatment:
ACTH, oral corticosteroids
Zonegran, Topamax
TSC
Vigabatrin

11. Other Seizures in TSC Partial complex seizures Generalized Seizures
Trileptal, Vimpa,t etc…
Generalized Seizures
Keppra, Dilantin, Depakote, etc…
Novel therapy
Ketogenic Diet

12. Tumors in TSC: SEGA SEGA Location Presentation:
Subependymal giant cell astrocytoma
Location
Foramen of Monroe
Presentation:
Headaches
Hydrocephalus

13. SEGA Treatment Surgical resection Chemotherapy
Novel agent, AFINITOR (everolimus)
mTOR inhibitor
mTOR is inactivated in TSC
AFINITOR can treat:
SEGA
AML
Adenoma sebaceum
Seizures?

14. Resources Tuberous Sclerosis Alliance TS Center at NEREG/HUMC
TS Center at NEREG/HUMC