Transcript to the powerpoint

What’s New in
Epilepsy
Research?
Evan Fertig, MD
Epileptologist
Director of Research
Northeast Regional Epilepsy Group
Outline
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Why is Epilepsy Research Important?
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What is a Clinical Trial?
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Epilepsy Medications under Study at
NEREG
New Surgical Approaches for
Epilepsy
Case #1: Why Epilepsy
Research is Important
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Todd age 15
Grand mal seizures
occur daily
Last MD told mom
nothing else to do
He is on 2 antiseizure
medications with
bad side effects,
doing poorly in
school
More about Todd…
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One of his
medication is
carbamazepine
which is a sodium
channel blocker
Video-EEG:
Seizures coming
from multiple areas
of his brain
MRI Brain: Normal
We learn that…
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Seizures began 6
months with fever
Seizures occur
more in the
summer or with
vigorous exercise
(gym)
New genetic blood
test sent: sodium
channel mutation!
What’s Todd’s Diagnosis?
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Dravet Syndrome
Caused by a genetic problem with a
brain protein (sodium channel). This
was not understood before!
Symptoms: Bad febrile seizures,
then multiple sz types, worsens with
sodium channel blockers
And so what happened?
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Carbamazepine is stopped (the
sodium channel blocker), Atkins Diet
(like the ketogenic diet) started.
Seizure free for 2 years
No side effects, doing very well in
school
Progress in Epilepsy Treatment
Requires Teamwork between Patients
Families agree
and MDs
to genetic
testing
(bloodwork)
Todd’s Success
with Diet
treatment!
• Dravet Mutation
Found!
Families with
Dravet
Mutation agree
to participate
in Diet Studies
• Benefit Seen!
Key Points
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The better we understand the causes
of epilepsy…
The better our treatments will be!
Clinical Research is the key but can’t
happen without teamwork between
patients, families, and MD’s
What is Epilepsy?
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A disorder of spontaneously
occurring unprovoked seizures (more
than 2)
Seizures are electrical storms of
brain cells that can cause many
different symptoms
How do Neurons (Brain Cells)
work?
Ion Channel
Sodium
Channel:
Excites!
Potassium,
Choride
Channel:
Rests!
What causes Seizures?
Brain
Tumors, Scar
tissue, etc.
Ion Channel
Problems
Excessive firing
SEIZURE
How Do Seizure Medication
Work?
Block release
Close Sodium
Channels
(CBZ)
Open Chloride
Channels
(gabapentin)
Excessive firing
SEIZURE
What are the Limits of Medical
Therapy?
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Trial and Error
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Brain Side Effects
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Body Side Effects
Seizure Control
How do We Move Forward?
Clinical
Trials
Basic
Science
FDA
ApprovalMedication
available for
public
Clinical Trials
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What is a clinical trial?
Key terms (from Epilepsy Study
Consortium)
• Randomization and Control
• Blinding
• Placebo
What Should I Know?
•Previous safety record of study
medication or device
•Chance of getting it vs. placebo?
•How long? What to expect at
each visit?
•Access to study agent after the
trial?
What Are Some Promising New
Medical Treatments under study
at NEREG?
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Everyday
Treatment
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Emergency
Treatment
• Lacosamide
(Vimpat)
• Intranasal
Midazolam
• Ezogabine (Potiga)
• Intrabuccal
Diazepam
• Pregabalin (Lyrica)
• Diet Therapies
• IV Brivaracetam
Potiga
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Potassium Channel
Opener
Partial Seizures
Rare but serious
side effects
Bottom Line
Potiga vs. Placebo in the Adjunctive
Treatment of Subjects with Partial Onset
Seizures (POS)
Objective
Requirement
Study
Procedure
• How safe and effective is Potiga in
adults with POS with poorly
controlled seizures?
•
Age > 18, 1 AED (no VNS or KD), 3
or more sz per month
• Visits to Hackensack office over 31
weeks. All medication, visits, and
travel are provided for free + stipend
Cognitive and Behavioral Effects of
Lacosamide (Vimpat) for POS. PI- Marcelo
Lancman, MD
Objective
Requirement
Study
Procedure
• How does the new medicine Vimpat affect
thinking (cognition) and mood (behavior)?
• Age > 18, English, 2 or more sz per month
• Visits to Hackensack office over 36 weeks.
All medications, visits, and
neuropsychological testing are provided for
free plus stipend
Effect of Lyrica on Anxiety in POS
Objective
Requirement
Study
Procedure
• How safe and effective is Lyrica
for Anxiety in Patients with
poorly controlled POS?
• Age > 18, 1-2 AEDs, not
presently treated for anxiety
• Visits to Hackensack office over
6 weeks. All medication, visits,
travel free plus stipend
Emergency Treatment
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Rectal Diastat
• Clinically proven
• Hard to give
• Social Stigma
• Can’t self
administer
Intranasal Midazolam
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Easy to give
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Preferred route
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Can be selfadministered or
given by caretaker
Under study
Intranasal Midazolam (IM)
Objective
• How safe and effective IM for
Seizure Clusters?
Requirement
• Age 14-22, Seizure Clusters
Study
Procedure
• One visit to Hackensack Hospital
for test dose then follow up
visits. Travel and meds are free
Intrabuccal Diazepam (Valium)
Objective
• How safe is Valium given in the
mouth for seizure clusters?
Requirement
• Age > 2, epilepsy with a
history of at least 1 grand mal
seizure, to be admitted to EMU
Study
Procedure
• IV line is placed, med is given
after a seizure, blood is taken
off the IV line several times
What are the Limits of Surgical
Therapy?
What’s on the Horizon?
When Do We Consider
Resective Epilepsy Surgery?
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Partial Epilepsy
Treatment Resistant Epilepsy
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Failure to become seizure free after > 2 adequate
trials of 2 AEDs used appropriately
Intolerable adverse effects of AEDs?
Why?
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Rate of Seizure Freedom with continued trials of
Sz med is low (5%)
Potential for injury with uncontrolled epilepsy
over a lifetime is high!
Rate of Seizure Control with Resective Epilepsy
Surgery is in comparison is high (30-80%) with a
low complication rate
Reduction or Elimination of Sz med is frequently
possible
How does Epilepsy surgery
work?
Brain
Tumors, Scar
tissue, etc.
Excessive firing
SEIZURE
Epilepsy Surgery
http://www.rch.unimelb.edu.au/cep/Media/brain/mri6.jpg
http://www.fleni.org.ar/files/servicio_193_8
Rates of Surgical Success*
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Temporal Lobectomy
70-80%
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“Lesion” Resection
70-80%
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“Non-Lesional” Resection
30-50%
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Medical Management
5%
* Absence of Disabling Seizures
What are the Limits of Surgical
Therapy?
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Small risk: bleeding and infection
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Not effective for all seizures types
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Not effective if seizures are come
from more than one location
Not possible if seizures arise from
critical brain tissue (hand area)
Visualase
•Laser Treatment
•Evaluation is same as
for epilepsy surgery
No need for open brain
operation
Visualase
Implant
• Probe inserted in OR
• Transferred to MRI
Treatment
• Laser Treatment
• MRI monitors safety of
Laser Rx real-time
Follow up
• Probe Removed
• Patient can leave same
day
Neuromodulatory Treatments
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Device implanted to alter instead of
destroy brain tissue
Range of treatment possible:
Electrical, Cooling, local medications
• Limit body/brain side effects
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Improve brain function?
NeuroPace
Implant
• Device under skull
• Leads to seizure
focus
• Detects seizure
• Electrical treatment
Treatment
delivered
• MD reviews
• Fine tunes
Follow up
treatment
What will Epilepsy Care Look
Like in Future?
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Personalized Medical
Choices based on
genetics
Truly Anti-epileptic
therapy
Treatment directed
right at the seizure
focus
Research at NEREG
Jeff Politsky,
MD
• MEG
• Tumor and
Epilepsy
• Critical Care
EEG
Olga LabanGrant, MD
Lorna Myers,
PhD
• Women and
Epilepsy
• IV
Brivaracetam
and Seizures
• Non-Epileptic
Seizures
• Spanish and
Epilepsy
Eric Segal, MD
• Diet
Therapies for
Epilepsy
• Sleep and
Epilepsy
• Dravet
Syndrome
Conclusion
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In most cases, seizures can be well
controlled with medications with minimal
side effects
The correct diagnosis to guide treatment
is essential
Epilepsy is more than just seizures, and
the treatment may require a team
approach
Conclusion
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Some cases are
more difficult to
control, and
treatment with diet
therapy or surgery
may be used, or
clinical trials may
be an option
Please Contact Us for More
Information!
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Director of Research
Evan Fertig, MD
Clinical Research Coordinator
Munazza Malik, MD
(201) 343-6676
[email protected]
Shweta Malhotra, TBA