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 TSC: 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) Hamartin TSC2 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 A combination of findings is required 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 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: ACTH, oral corticosteroids Zonegran, Topamax TSC Vigabatrin

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

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

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

Resources Tuberous Sclerosis Alliance TS Center at NEREG/HUMC www.tsalliance.org TS Center at NEREG/HUMC