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 5+
Age 2+
Age 1+
Age 0-1
• Febrile
Seizures
• EEG
normal
• Other
seizure
types
appear
• EEG
abnormal
• Cognitive/
Behavior
problems
develop
• Seizures
may
become
less
frequent
• Cognitive
problems
plateau
Focal
Generalized
 Simple and Complex
 Myoclonic
Partial seizures
 Autonomic changes are
prominent
 Hemiclonic Seizures
 Generalized Tonic Clonic
 Myoclonic Absence
Seizures
 Triggered by flashing
lights
 Can be prolonged
 Atonic
SUDEP
Ortho
Behavior and
Development
Autism/ASD
↓Sweating
↑ Infections
Nutrition
Sleep
Get a History!
EEG and MRI
Genetic Testing positive in 7080% of cases
• Mutation in SCN1a gene
1953
1856
http://www.csiro.au
Genome
Chromosome
A Mutation is a SPELLING ERROR here
Cell
Gene
Protein
Mutation
Neuron Nih.gov
http://www.niaaa.nih.gov/NR/rdonlyres/9E5D5B9F-C28E-49F2-A925-33886A82E4D5/0/synapsebetween_neurons.gif
Ion Channel
Sodium Channel:
Excites!
Potassium, Choride
Channel:
Rests!
Febrile
Seizures
(FS)
ICE-GTC
SCN1A
SMEI/Dr
avet
Syndrom
e
GEFS+
PT/OT
Developmental
Specialist
Orthopediatist
Nutritonist
Neurologist
Seizure
Freedom
Development
Safety
• Antipyrexics
• Rescue Medication (benz0)
• Cooling vest for hot weather
• Avoid big change in temp
• Sunglasses: Zeiss Z1F133.
• Unilateral eye patching?
Wrong Meds
• Tegretol, Dilantin
• Lamictal, Rufinamide
Depakote
*Broad
spectrum
*Behavior
*Not typically
used under
age 2
*Side effects
Clobazam
Topamax
*Broad
Spectrum
*Broad
Spectrum
Side Effects
• Sedation
• Drooling
Cognitive Side
Effects
2 Sz free
16
continued
10 75-99%
decrease
4 50-74%
decrease
24 pt
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
“Convulsive
Seizures”
Myoclonic
Absence
•
•
•
•
Depakote
Clobazam
Stiripentol and Clobazam
Topamax
• Ketogenic Diet
• Ethosuximide
 No Magic Bullet for treatment
 Intense Research Efforts are Ongoing
 Dravet.org