1. Evan Fertig Director of Research Director of NEREG Dravet Program Northeast Regional Epilepsy Group

2. What is Dravet? How do we diagnosis it? Dravet Genetics How do we treat it?

3. 1978 C. Dravet describes SMEI 1989 Dravet Syndrome 2001 SCN1A mutation discovered

4. Age 0-1 Febrile Seizures EEG normal Age 1+ Other seizure types appear EEG abnormal Age 2+ Cognitive/ Behavior problems develop Age 5+ Seizures may become less frequent Cognitive problems plateau

5. Focal Simple and Complex Partial seizures Autonomic changes are prominent Hemiclonic Seizures Myoclonic Generalized Tonic Clonic Myoclonic Absence Seizures Triggered by flashing lights Can be prolonged Atonic Generalized

6. SUDEPOrtho Behavior and Development Autism/ASD ↓Sweating↑ Infections NutritionSleep

7. Get a History!EEG and MRI Genetic Testing positive in 70- 80% of cases Mutation in SCN1a gene

8. 1856 1953

9. http://www.csiro.au

10. http:// davidmaybury.ie Genome Chromosome A Mutation is a SPELLING ERROR here

11. Gene Protein Neuron Nih.gov Mutation Cell

12. http://www.niaaa.nih.gov/NR/rdonlyres/9E5D5B9F-C28E-49F2-A925-33886A82E4D5/0/synapsebetween_neurons.gif

13. Ion Channel Sodium Channel: Excites! Potassium, Choride Channel: Rests!

14. SCN1A Febrile Seizures (FS) GEFS+ SMEI/Dr avet Syndrom e ICE-GTC

16. PT/OT Developmental Specialist Nutritonist OrthopediatistNeurologist

17. Seizure Freedom Development Safety

18. Antipyrexics Rescue Medication (benz0) Cooling vest for hot weather Avoid big change in temp Sunglasses: Zeiss Z1F133. Unilateral eye patching? Tegretol, Dilantin Lamictal, Rufinamide Wrong Meds

20. Depakote *Broad spectrum *Behavior *Not typically used under age 2 *Side effects Clobazam *Broad Spectrum Side Effects Sedation Drooling Topamax *Broad Spectrum Cognitive Side Effects

21. 24 pt 16 continued 2 Sz free 10 75-99% decrease 4 50-74% decrease 8 stopped 5 not effective 3 vomiting Carabolla 2005

22. Only med with placebo controlled evidence Evidence of efficacy from 2 short-term and 1 long-term European studies Prescribed with Clobazam (onfi) +/- VPA (depakote)

23. Not FDA Approved Orphan Drug Status Medicaid Covered in some States

24. Blocks Clobazam “Metabolism” Increases level of medication and important “metabolite” in blood Enhances “GABA” SCN1A thought to effect GABA brain cells

25. 71 % vs. 5 %; Responders Almost half of the stiripentol recipients were seizure free during this period compared with none in the placebo group.

26. 21 patients on stiripentol had moderate side-effects (drowsiness, loss of appetite) compared with eight on placebo, but side-effects disappeared when the dose of comedication was decreased in 12 of the 21 cases. Drug interactions Clobazam Depakote Neutropenia

28. Comes in 250 mg or 500 mg capsule, or sachet Taken twice or three times a day Lower Clobazam by 20% before dosing No need to change depakote dose

29. Keppra Zonegran Bromides VNS Felbamate Steroids? IVIG? NOT effective: Resective Epilepsy Surgery

30. Depakote Clobazam Stiripentol and Clobazam Topamax “Convulsive Seizures” Ketogenic Diet Ethosuximide Myoclonic Absence

31. No Magic Bullet for treatment Intense Research Efforts are Ongoing Dravet.org