dravet syndrome disorders

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

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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 Presentation

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Page 1: Dravet Syndrome Disorders

Evan FertigDirector of Research

Director of NEREG Dravet ProgramNortheast Regional Epilepsy Group

Dravet Syndrome Disorders

Page 2: Dravet Syndrome Disorders

What is Dravet?

How do we diagnosis it?Dravet Genetics

How do we treat it?

Outline

Page 3: Dravet Syndrome Disorders

1978C. Dravet

describes SMEI1989

Dravet Syndrome2001

SCN1A mutation discovered

A Brief History of Dravet Syndrome

Page 4: Dravet Syndrome Disorders

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

Page 5: Dravet Syndrome Disorders

FocalSimple and Complex

Partial seizuresAutonomic changes

are prominent

Hemiclonic Seizures

MyoclonicGeneralized Tonic

ClonicMyoclonic Absence

SeizuresTriggered by

flashing lightsCan be prolonged

Atonic

Dravet Seizure TypesGeneralized

Page 6: Dravet Syndrome Disorders

SUDEP Ortho Behavior and Development

Autism/ASD ↓Sweating ↑

Infections

Nutrition Sleep

Conditions Associated with Dravet(Dravet.org)

Page 7: Dravet Syndrome Disorders

Get a History!

EEG and MRI

Genetic Testing positive in 70-80% of cases• M

utation in SCN1a gene

How Do We Diagnosis Dravet?

Page 8: Dravet Syndrome Disorders

Peas, Genes, and DNA

18561953

Page 9: Dravet Syndrome Disorders

What is a Gene?

http://www.csiro.au

Page 10: Dravet Syndrome Disorders

The Structure of the Genome

GENEGenome

Chromosome

A Mutation is a SPELLING ERROR here

Page 11: Dravet Syndrome Disorders

Genes, Protein, and Disease

Gene Protein

Neuron Nih.gov

Mutation

Cell

Page 12: Dravet Syndrome Disorders

Brain Communication

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

Page 13: Dravet Syndrome Disorders

How do Neurons (Brain Cells) work?

Ion Channel

Sodium Channel: Excites!

Potassium, Choride Channel: Rests!

Page 14: Dravet Syndrome Disorders

SCN1A

Febrile Seizures

(FS)

GEFS+SMEI/Dravet

Syndrome

ICE-GTC

SCN1A-related seizure disorders

Page 15: Dravet Syndrome Disorders

Treatment of Dravet Syndrome

Page 16: Dravet Syndrome Disorders

PT/OT Developmental Specialist

Nutritonist

Orthopediatist

Neurologist

How do we Treat Dravet: Teamwork

Page 17: Dravet Syndrome Disorders

Seizure Freedom

Development

Safety

Dravet Anti-Seizure Treatment Goals

Page 18: Dravet Syndrome Disorders

•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

Page 19: Dravet Syndrome Disorders

Should children with Dravet get Vaccines?

Page 20: Dravet Syndrome Disorders

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

Page 21: Dravet Syndrome Disorders

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

Page 22: Dravet Syndrome Disorders

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)

Page 23: Dravet Syndrome Disorders

Not FDA Approved

Orphan Drug Status

Medicaid Covered in some States

Page 24: Dravet Syndrome Disorders

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?

Page 25: Dravet Syndrome Disorders

 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

Page 26: Dravet Syndrome Disorders

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

Page 27: Dravet Syndrome Disorders

How Stiripentol is Taken

Page 28: Dravet Syndrome Disorders

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

Page 29: Dravet Syndrome Disorders

KeppraZonegranBromidesVNSFelbamateSteroids?IVIG?

NOT effective: Resective Epilepsy Surgery

Possible Efficacy?

Page 30: Dravet Syndrome Disorders

“Convulsive

Seizures”

•Depakote•Clobazam•Stiripentol and Clobazam•Topamax

Myoclonic Absence

•Ketogenic Diet•Ethosuximide

Treatment Approach

Page 31: Dravet Syndrome Disorders

No Magic Bullet for treatment

Intense Research Efforts are Ongoing

Dravet.org

Conclusion