What’s New in What’s New in Epilepsy Epilepsy

Research?Research?Evan Fertig, MDEvan Fertig, MD

Epileptologist Epileptologist Director of ResearchDirector of Research

Northeast Regional Epilepsy GroupNortheast Regional Epilepsy Group

Evan Fertig, MDEvan Fertig, MD

Epileptologist Epileptologist Director of ResearchDirector of Research

Northeast Regional Epilepsy GroupNortheast Regional Epilepsy Group

OutlineOutline

Why is Epilepsy Research Important?Why is Epilepsy Research Important?

What is a Clinical Trial?What is a Clinical Trial?

Epilepsy Medications under Study at Epilepsy Medications under Study at NEREGNEREG

New Surgical Approaches for EpilepsyNew Surgical Approaches for Epilepsy

Case #1: Why Epilepsy Case #1: Why Epilepsy Research is ImportantResearch is Important

Todd age 15Todd age 15 Grand mal seizures Grand mal seizures

occur dailyoccur daily Last MD told mom Last MD told mom

nothing else to donothing else to do He is on 2 anti-He is on 2 anti-

seizure medications seizure medications with bad side with bad side effects, doing effects, doing poorly in schoolpoorly in school

More about Todd…More about Todd…

One of his One of his medication is medication is carbamazepine carbamazepine which is a which is a sodium sodium channel blockerchannel blocker

Video-EEG: Seizures Video-EEG: Seizures coming from multiple coming from multiple areas of his brainareas of his brain

MRI Brain: NormalMRI Brain: Normal

We learn that…We learn that… Seizures began 6 Seizures began 6

months with fevermonths with fever

Seizures occur more Seizures occur more in the summer or in the summer or with vigorous with vigorous exercise (gym)exercise (gym)

New genetic blood New genetic blood test sent: test sent: sodium sodium channel mutationchannel mutation!!

What’s Todd’s Diagnosis?What’s Todd’s Diagnosis?

Dravet SyndromeDravet Syndrome

Caused by a genetic problem with a Caused by a genetic problem with a brain protein (sodium channel). brain protein (sodium channel). This This was not understood before!was not understood before!

Symptoms: Bad febrile seizures, then Symptoms: Bad febrile seizures, then multiple sz types, worsens with sodium multiple sz types, worsens with sodium channel blockerschannel blockers

And so what happened?And so what happened?

Carbamazepine is stopped (the Carbamazepine is stopped (the sodium channel blocker), Atkins Diet sodium channel blocker), Atkins Diet (like the ketogenic diet) started. (like the ketogenic diet) started.

Seizure free for 2 yearsSeizure free for 2 years

No side effects, doing very well in No side effects, doing very well in schoolschool

Progress in Epilepsy Treatment Progress in Epilepsy Treatment Requires Teamwork between Patients Requires Teamwork between Patients

and MDsand MDs

Key PointsKey Points

The better we understand the causes The better we understand the causes of epilepsy…of epilepsy…

The better our treatments will be!The better our treatments will be!

Clinical Research is the key but can’t Clinical Research is the key but can’t happen without teamwork between happen without teamwork between patients, families, and MD’spatients, families, and MD’s

What is Epilepsy?What is Epilepsy?

A disorder of spontaneously A disorder of spontaneously occurring unprovoked seizures (more occurring unprovoked seizures (more than 2)than 2)

Seizures are electrical storms of Seizures are electrical storms of brain cells that can cause many brain cells that can cause many different symptomsdifferent symptoms

How do Neurons (Brain Cells) How do Neurons (Brain Cells) work?work?

Ion Channel

Sodium Channel: Excites!

Potassium, Choride Channel: Rests!

What causes Seizures?What causes Seizures?

Ion ChannelProblems

Brain Tumors, Scar tissue, etc.

Excessive firing

SEIZURE

How Do Seizure Medication How Do Seizure Medication Work?Work?

Close Sodium Channels (CBZ)

Open Chloride Channels (gabapentin)

Block release

Excessive firing

SEIZURE

What are the Limits of Medical What are the Limits of Medical Therapy?Therapy?

Trial and ErrorTrial and Error

Brain Side EffectsBrain Side Effects

Body Side EffectsBody Side Effects

Seizure ControlSeizure Control

How do We Move Forward?How do We Move Forward?

Clinical TrialsClinical Trials

What is a clinical trial?What is a clinical trial?

Key terms (from Epilepsy Study Key terms (from Epilepsy Study Consortium)Consortium)• Randomization and ControlRandomization and Control

• BlindingBlinding

• PlaceboPlacebo

What Should I Know?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 What Are Some Promising New Medical Treatments under study Medical Treatments under study

at NEREG?at NEREG? Everyday TreatmentEveryday Treatment

• Lacosamide (Vimpat)Lacosamide (Vimpat)

• Ezogabine (Potiga)Ezogabine (Potiga)

• Pregabalin (Lyrica)Pregabalin (Lyrica)

• Diet TherapiesDiet Therapies

Emergency Emergency TreatmentTreatment

• Intranasal Intranasal MidazolamMidazolam

• Intrabuccal Intrabuccal DiazepamDiazepam

• IV BrivaracetamIV Brivaracetam

PotigaPotiga

Potassium Channel Potassium Channel OpenerOpener

Partial SeizuresPartial Seizures

Rare but serious Rare but serious side effectsside effects

Bottom LineBottom Line

Potiga vs. Placebo in the Adjunctive Potiga vs. Placebo in the Adjunctive Treatment of Subjects with Partial Onset Treatment of Subjects with Partial Onset

Seizures (POS)Seizures (POS)

Cognitive and Behavioral Effects of Cognitive and Behavioral Effects of Lacosamide (Vimpat) for POS. Lacosamide (Vimpat) for POS. PI- Marcelo PI- Marcelo

Lancman, MDLancman, MD

Effect of Lyrica on Anxiety in POSEffect of Lyrica on Anxiety in POS

Emergency TreatmentEmergency Treatment

Rectal DiastatRectal Diastat

• Clinically provenClinically proven

• Hard to giveHard to give

• Social StigmaSocial Stigma

• Can’t self Can’t self administeradminister

Intranasal MidazolamIntranasal Midazolam

Easy to giveEasy to give

Preferred routePreferred route

Can be self-Can be self-administered or administered or given by caretakergiven by caretaker

Under studyUnder study

Intranasal Midazolam (IM)Intranasal Midazolam (IM)

Intrabuccal Diazepam (Valium)Intrabuccal Diazepam (Valium)

What are the Limits of Surgical What are the Limits of Surgical Therapy?Therapy?

What’s on the Horizon?What’s on the Horizon?

When Do We ConsiderWhen Do We ConsiderResective Epilepsy Surgery?Resective Epilepsy Surgery?

Partial EpilepsyPartial Epilepsy

Treatment Resistant EpilepsyTreatment Resistant Epilepsy Failure to become seizure free after Failure to become seizure free after >> 2 2 adequateadequate

trials of 2 AEDs used appropriatelytrials of 2 AEDs used appropriately

Intolerable adverse effects of AEDs?Intolerable adverse effects of AEDs?

Why?Why?

Rate of Seizure Freedom with continued trials of Sz Rate of Seizure Freedom with continued trials of Sz med is low (5%)med is low (5%)

Potential for injury with uncontrolled epilepsy over a Potential for injury with uncontrolled epilepsy over a lifetime is high!lifetime is high!

Rate of Seizure Control with Resective Epilepsy Rate of Seizure Control with Resective Epilepsy Surgery is in comparison is high (30-80%) with a low Surgery is in comparison is high (30-80%) with a low complication ratecomplication rate

Reduction or Elimination of Sz med is frequently Reduction or Elimination of Sz med is frequently possiblepossible

How does Epilepsy surgery How does Epilepsy surgery work?work?

Brain Tumors, Scar tissue, etc.

Excessive firing

SEIZURE

Epilepsy SurgeryEpilepsy Surgery

http://www.rch.unimelb.edu.au/cep/Media/brain/mri6.jpghttp://www.fleni.org.ar/files/servicio_193_8

Rates of Surgical Success*Rates of Surgical Success*

Temporal Lobectomy 70-80%Temporal Lobectomy 70-80%

““Lesion” Resection 70-80%Lesion” Resection 70-80%

““Non-Lesional” Resection 30-50%Non-Lesional” Resection 30-50%

Medical Management 5%Medical Management 5%

* Absence of Disabling Seizures

What are the Limits of Surgical What are the Limits of Surgical Therapy?Therapy?

Small risk: bleeding and infectionSmall risk: bleeding and infection

Not effective for all seizures typesNot effective for all seizures types

Not effective if seizures are come from Not effective if seizures are come from more than one locationmore than one location

Not possible if seizures arise from critical Not possible if seizures arise from critical brain tissue (hand area)brain tissue (hand area)

VisualaseVisualase

•Laser Treatment

•Evaluation is same asfor epilepsy surgery

No need for open brainoperation

VisualaseVisualase

Neuromodulatory TreatmentsNeuromodulatory Treatments

Device implanted to alter instead of Device implanted to alter instead of destroy brain tissuedestroy brain tissue

Range of treatment possible: Range of treatment possible: Electrical, Cooling, local medicationsElectrical, Cooling, local medications• Limit body/brain side effectsLimit body/brain side effects

Improve brain function?Improve brain function?

NeuroPaceNeuroPace

What will Epilepsy Care Look What will Epilepsy Care Look Like in Future?Like in Future?

Personalized Medical Personalized Medical Choices based on Choices based on geneticsgenetics

Truly Truly Anti-epilepticAnti-epileptic therapytherapy

Treatment directed Treatment directed right at the seizure right at the seizure focusfocus

Research at NEREGResearch at NEREG

ConclusionConclusion

In most cases, seizures can be well In most cases, seizures can be well controlled with medications with minimal controlled with medications with minimal side effects side effects

The correct diagnosis to guide treatment is The correct diagnosis to guide treatment is essentialessential

Epilepsy is more than just seizures, and the Epilepsy is more than just seizures, and the treatment may require a treatment may require a teamteam approach approach

ConclusionConclusion

Some cases are Some cases are more difficult to more difficult to control, and control, and treatment with diet treatment with diet therapy or surgery therapy or surgery may be used, or may be used, or clinical trials may clinical trials may be an optionbe an option

Please Contact Us for More Please Contact Us for More Information!Information!

Director of ResearchDirector of ResearchEvan Fertig, MDEvan Fertig, MD

Clinical Research CoordinatorClinical Research CoordinatorMunazza Malik, MDMunazza Malik, MD(201) 343-6676(201) 343-6676munazza.malik@gmail.communazza.malik@gmail.com

Shweta Malhotra, TBAShweta Malhotra, TBA