dravet syndrome disorders
DESCRIPTION
Dravet Syndrome Disorders. Evan Fertig Director of Research Director of NEREG Dravet Program Northeast Regional Epilepsy Group. Outline. What is Dravet ? How do we diagnosis it ? Dravet Genetics How do we treat it?. A Brief History of Dravet Syndrome. Dravet Life Timeline. - PowerPoint PPT PresentationTRANSCRIPT
Evan FertigDirector of Research
Director of NEREG Dravet ProgramNortheast Regional Epilepsy Group
Dravet Syndrome Disorders
What is Dravet?
How do we diagnosis it?Dravet Genetics
How do we treat it?
Outline
1978C. Dravet
describes SMEI1989
Dravet Syndrome2001
SCN1A mutation discovered
A Brief History of Dravet Syndrome
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
Dravet Life Timeline
FocalSimple and Complex
Partial seizuresAutonomic changes
are prominent
Hemiclonic Seizures
MyoclonicGeneralized Tonic
ClonicMyoclonic Absence
SeizuresTriggered by
flashing lightsCan be prolonged
Atonic
Dravet Seizure TypesGeneralized
SUDEP Ortho Behavior and Development
Autism/ASD ↓Sweating ↑
Infections
Nutrition Sleep
Conditions Associated with Dravet(Dravet.org)
Get a History!
EEG and MRI
Genetic Testing positive in 70-80% of cases• M
utation in SCN1a gene
How Do We Diagnosis Dravet?
Peas, Genes, and DNA
18561953
What is a Gene?
http://www.csiro.au
The Structure of the Genome
GENEGenome
Chromosome
A Mutation is a SPELLING ERROR here
Genes, Protein, and Disease
Gene Protein
Neuron Nih.gov
Mutation
Cell
Brain Communication
http://www.niaaa.nih.gov/NR/rdonlyres/9E5D5B9F-C28E-49F2-A925-33886A82E4D5/0/synapsebetween_neurons.gif
How do Neurons (Brain Cells) work?
Ion Channel
Sodium Channel: Excites!
Potassium, Choride Channel: Rests!
SCN1A
Febrile Seizures
(FS)
GEFS+SMEI/Dravet
Syndrome
ICE-GTC
SCN1A-related seizure disorders
Treatment of Dravet Syndrome
PT/OT Developmental Specialist
Nutritonist
Orthopediatist
Neurologist
How do we Treat Dravet: Teamwork
Seizure Freedom
Development
Safety
Dravet Anti-Seizure Treatment Goals
•Antipyrexics•Rescue Medication (benz0)
•Cooling vest for hot weather•Avoid big change in temp
•Sunglasses: Zeiss Z1F133.•Unilateral eye patching?
•Tegretol, Dilantin•Lamictal, RufinamideWrong Meds
Avoid Seizure Triggers
Should children with Dravet get Vaccines?
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
First Line Medicines for Dravet Syndrome in the United States
24 pt
16 continued
2 Sz free
10 75-99% decrease
4 50-74% decrease
8 stopped
5 not effective
3 vomiting
Ketogenic Diet for Dravet Syndrome
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)
Stiripentol (Diacomnit)
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
How Does Stiripentol Work?
71 % vs. 5 %; Responders
Almost half of the stiripentol recipients were seizure free during this period compared with none in the placebo group.
Stiripentol Study
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 interactionsClobazam
DepakoteNeutropenia
Side Effects and Interactions
How Stiripentol is Taken
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
Stiripentol dosing
KeppraZonegranBromidesVNSFelbamateSteroids?IVIG?
NOT effective: Resective Epilepsy Surgery
Possible Efficacy?
“Convulsive
Seizures”
•Depakote•Clobazam•Stiripentol and Clobazam•Topamax
Myoclonic Absence
•Ketogenic Diet•Ethosuximide
Treatment Approach
No Magic Bullet for treatment
Intense Research Efforts are Ongoing
Dravet.org
Conclusion