Dravet`s Syndrome explained - Dr. Evan Fertig
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Transcript Dravet`s Syndrome explained - Dr. Evan Fertig
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