Advances in the
Treatment of Epilepsy
Olgica Laban-Grant, MD
Northeast Regional Epilepsy Group
epilepsygroup.com
Epilepsy
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Epilepsy is one of the most common
neurological diseases.
It affects all ages, races & ethnic
backgrounds
It affects approximately 0.5-2% of the
population (2.7 million Americans).
Every year, approximately 200,000
people develop epilepsy
Seizures
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Up to 5% of the population may
have a single seizure at some time
in their lives.
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Seizures may be symptom of
different disorders
Seizures
The healthy brain consists of millions
of interconnecting nerve cells called
neurons.
 Neurons are constantly
communicating with each other by
sending signals through tentacle-like
connections called axons and
dendrites
Anti-Epileptic Medications
Seizures
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Neurons normally generate impulses
up to 80 times a second.
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During an epileptic seizure, that rate
can increase to up to 500 times a
second.
What Is Epilepsy?
Epilepsy is the term applied to the
state of recurrent seizures.
 If you had two seizures there is 80%
chance you will have more.
 Epilepsy is usually diagnosed when
person had at least two seizures
that were not caused by known
medical condition.
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Seizure
Single seizure
5-10%
vs.
Epilepsy
Recurrent seizures
0.5-2%
Why EEG
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EEG as predictor of the risk of
recurrence within two years of first
seizure
epileptic discharges - 83%
 nonepileptic abnormalities -41%
 Normal – 12%
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Epilepsy
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Epilepsy is a tremendously variable
condition in terms of its cause,
seizure types and response to
treatment.
Trteatment
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Depends on many factors:
Age
 Type of seizures
 Type of epilepsy
 Medical history
 Frequency and severity of seizures
 Available drug formulations of
medications
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Treating Epilepsy
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The goal in treating epilepsy is
No seizures
 No side effects
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Treating Epilepsy
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First line treatment is medication
Surgery and surgical devices
Diet
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Lifestyle (avoiding trigger factors)
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Medications
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Medications do not cure epilepsy,
rather they control epilepsy by
suppressing the seizures.
Medications
Brain function is result of fine balance
of activation and suppression of
neuron activity.
Balance is maintained by chemicals in
brain called neurotransmitters.
Medications are designed to
reestablish balance among
chemicals in brain.
AED Therapy
Epilepsy
Time
First AED
Increase
Dosage
Switch
AED
Combine
AEDs
Polytherapy
Trial and Error Method
Response to AEDs
PharMetrics. April 2002 to June 2003
IMS NPA, Dec 2003.
Kwan P, Brodie MJ. N Engl J Med 2000; 342: 314-9.
Combine medications with different mechanism of
action
Anti-Epileptic Medications
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ACTH (ACthar gel)
Acteozalamide (Diamox)
Carbamazepine (Tegretol,
Carbatrol)
Clonazepam (Klonopin)
Ethosuxsimide (Zarontin)
Felbamate (Felbatol)
Gabapentin (Neurontin)
Gabitril (Tiagabine)
Lacosamide (Vimpat)
Lamotrigine (Lamictal)
Levatiracetam (Keppra)
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Mysoline (Primidone)
Oxcarbazepine (Trileptal)
Phenobarbital
Phenytoin (Dilantin)
Pregabalin (Lyrica)
Rufinamide (Banzel)
Topiramate (Topamax)
Tranxene
Valproic acid (Depakote)
Vigabatrin (Sabril)
Zonisamide (Zonegran)
Ezogabine (Potiga)
Anti-Epileptic Medications
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ACTH (ACthar gel)
Actelozamide (Diamox)
Carbamazepine (Tegretol,
Carbatrol)
Clonazepam (Klonopin)
Ethosuxsimide (Zarontin)
Felbamate (Felbatol)
Gabapentin (Neurontin)
Gabitril (Tiagabine)
Lacosamide (Vimpat)
Lamotrigine (Lamictal)
Levatiracetam (Keppra)
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Mysoline (Primidone)
Oxcarbazepine (Trileptal)
Phenobarbital
Phenytoin (Dilantin)
Pregabalin (Lyrica)
Rufinamide (Banzel)
Topiramate (Topamax)
Tranxene
Valproic acid (Depakote)
Vigabatrin (Sabril)
Zonisamide (Zonegran)
Ezogabine (Potiga)
Lacosamide (Vimpat)
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FDA approved in 2008
Epilepsy treatment for partial-onset
seizures in patients who are 17years
and older.
 It is a medication that can be added
to any other antiseizure medication
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International League Against Epilepsy
(ILEA)
Classification of Seizures
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Partial (Focal)
Seizures
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Simple Partial
Complex Partial
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Generalized
Seizures
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Absence
Myoclonic
Clonic
Tonic
Tonic-Clonic
Atonic
Partial Seizures
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Simple Partial: No impairment of
consciousness.
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Complex Partial: Altered awareness
Lacosamide (Vimpat)
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Approximately 40% of patients in
clinical studies had their partialonset seizures reduced by half or
more.
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More seizure-free days
Lacosamide (Vimpat)
Mechanism of action
 Enhances the number of sodium
channels entering into the slow
inactivated state
 Does not affect activity mediated by
fast inactivation
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Anti-Epileptic Medications
Dilantin
 Tegretol
 Trileptal
 Zonegran
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Vimpat
Lacosamide
(Vimpat)
Lacosamide (Vimpat)
Side effects
 Depression 1:500
 Dizziness, double vision, sleepiness,
problems with coordination
 Irregular heartbeat (may prolong PR
interval on EKG)
 No effect on weight
 No effect on memory
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Banzel (Rufinamide)
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FDA approved in 2008
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Indicated for add on treatment of
seizures associated with LennoxGastaut syndrome in children 4
years and older and adults.
Lennox-Gastaut syndrome
1-4% of childhood epilepsies
 Different types of seizures (tonic,
atonic, myoclonic, generalized
seizures)
 Mental retardation
 Specific EEG pattern
 Difficult to treat
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Banzel (Rufinamide)
reduction in total seizure number
 42.5% median percentage reduction
in tonic-atonic seizure (drop attack)
 significant improvement in seizure
severity
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Banzel (Rufinamide)
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Reports on decrease of frequency of
partial seizures –medication is not
approved for this indication.
Total partial seizures were reduced by
23.3% rufinamide and by 9.8% with
placebo (86% were taking at least two
drugs)
Banzel (Rufinamide)
The exact mechanism of action is
unknown.
 Modulates the activity of sodium
channels and, in particular,
prolongation of the inactive state of
the channel.
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Banzel (Rufinamide)
Side effects
 Depression 1:500
 Dizziness, double vision, sleepiness,
problems with coordination
 May make the contraception less
effective
 It is contraindicated in familial short
QT syndrome-EKG prior to starting it
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Sabril (Vigabatrin)
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FDA approved in 2009
Refractory complex partial seizures
 Infantile spasms (IS) - babies
between the ages of 1 month and 2
years
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Infantile spasms
Onset typically 4-8 months
 infantile spasms
 developmental regression
 specific pattern on EEG called
hypsarrhythmia (chaotic brain
waves)
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Sabril (Vigabatrin)
Mechanism of action
 Preventing breaking down of GABA.
GABA is chemical that suppresses
activity in neurons.
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Anti-Epileptic Medications
Sabril (Vigabatrin)
Side effects
 It may permanently damage the
vision. The most noticeable loss is in
the ability to see to the side when
looking straight ahead (peripheral
vision).
 Occurred in 30% or more of patient.
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Ezogabine (Potiga)
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Adjunctive therapy in partial-onset
seizures uncontrolled by current
medications in adults
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FDA approved in 2011 but not
available yet in USA
Ezogabine (Potiga)
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Novel mechanism of action
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Potassium channel opener
Ezogabine (Potiga)
Side effects
 dizziness, fatigue, tremor, problems
with coordination, double vision
 memory impairment
 lack of strength.
 urinary retention
 confusion, hallucinations
 depression
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Other Treatments
Diet
Epilepsy Surgery
The Ketogenic Diet
A medically prescribed, strict
dietary regimen used for the
refractory pediatric patient
Ketogenic Diet
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Mimics the metabolic effects of starvation
Used primarily to treat severe childhood
epilepsy that has not responded to
standard antiseizure drugs
Diet includes high fat content, no sugar
and low carbohydrate and protein intake
The Ketogenic diet
side effects
Dehydration, constipation, kidney
stones or gall stones, pancreatitis,
decreased bone density, menstrual
irregularities.
 vitamins have to be added through
supplements.
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Diet in adults
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Ketogenic diet is not typically offered to
adults with epilepsy due to the significant
lifestyle alterations needed for its use
A modified Atkins diet appears to
demonstrate preliminary efficacy for
adults with intractable epilepsy, especially
in those who lost weight.
Modified Atkins
allowance of more carbohydrates
than in ketogenic diet but less than
in Atkins diet (10-20g)
 More fat than in Atkins diet
 high-protein diet
 no caloric or fluid restrictions
 no weighing or measuring of foods
 no admission fast is required
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Goals of Epilepsy Surgery
To eradicate or significantly reduce
the amount and severity of seizures
 To minimize the disability secondary
to seizures
 To address quality of life issues
 To decrease medication
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Surgical devices
Vagus Nerve Stimulator
 Deep Brain Stimulation
 Neuropace
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Surgical devices
Vagus Nerve Stimulator
 Deep Brain Stimulation
 Neuropace
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Deep Brain stimulation
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stimulating
electrode is
implanted in the
brain (anterior
nuclei of thalamus)
56% reduction in
seizure frequency
FDA approved for
patients with
severe and
refractory partial
seizures
Neuropace
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responsive
neurostimulator
which is implanted
in the brain,
detects abnormal
electrical activity
and sends out
electrical impulses
to prevent seizures
Clinical trials
started
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THANK YOU!
Northeast Regional Epilepsy Group
epilepsygroup.com