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

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

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

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

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

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

Get a History!EEG and MRI Genetic Testing positive in % of cases Mutation in SCN1a gene

davidmaybury.ie Genome Chromosome A Mutation is a SPELLING ERROR here

Gene Protein Neuron Nih.gov Mutation Cell

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

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

PT/OT Developmental Specialist Nutritonist OrthopediatistNeurologist

Seizure Freedom Development Safety

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

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

24 pt 16 continued 2 Sz free % decrease % decrease 8 stopped 5 not effective 3 vomiting Carabolla 2005

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)

Not FDA Approved Orphan Drug Status Medicaid Covered in some States

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

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

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

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

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

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

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