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Advances in theTreatment of Epilepsy
OlgicaOlgica Laban-GrantLaban-Grant, , MDMD
Northeast Regional Epilepsy Group
epilepsygroup.com
Epilepsy
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
Up to 5% of the population may have a single seizure at some time in their lives.
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
Neurons normally generate impulses up to 80 times a second.
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.
Single seizure Recurrent seizures5-10% 0.5-2%
Seizure vs. Epilepsy
Why EEG EEG as predictor of the risk of
recurrence within two years of first seizure epileptic discharges - 83% nonepileptic abnormalities -41% Normal – 12%
Epilepsy
Epilepsy is a tremendously variable condition in terms of its cause, seizure types and response to treatment.
Trteatment
Depends on many factors: Age Type of seizures Type of epilepsy Medical history Frequency and severity of seizures Available drug formulations of
medications
Treating Epilepsy
The goal in treating epilepsy is No seizures No side effects
Treating Epilepsy
First line treatment is medication Surgery and surgical devices Diet
Lifestyle (avoiding trigger factors)
Medications
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 TherapyEpilepsy
First AEDIncrease Dosage
Switch AED
Combine AEDs
Polytherapy
Trial and Error MethodTrial and Error Method
Time
Response to AEDs
PharMetrics. April 2002 to June 2003IMS 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 ACTH (ACthar gel) Acteozalamide (Diamox) Carbamazepine (Tegretol,
Carbatrol) Clonazepam (Klonopin) Ethosuxsimide (Zarontin) Felbamate (Felbatol) Gabapentin (Neurontin) Gabitril (Tiagabine) Lacosamide (Vimpat) Lamotrigine (Lamictal) Levatiracetam (Keppra)
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 ACTH (ACthar gel) Actelozamide (Diamox) Carbamazepine (Tegretol,
Carbatrol) Clonazepam (Klonopin) Ethosuxsimide (Zarontin) Felbamate (Felbatol) Gabapentin (Neurontin) Gabitril (Tiagabine) Lacosamide (Vimpat) Lamotrigine (Lamictal)
Levatiracetam (Keppra)
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) 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
International League Against Epilepsy (ILEA) Classification of Seizures
Partial (Focal) Seizures Simple Partial Complex Partial
Generalized Seizures Absence Myoclonic Clonic Tonic Tonic-Clonic Atonic
Partial Seizures
Simple Partial: No impairment of consciousness.
Complex Partial: Altered awareness
Lacosamide (Vimpat) Approximately 40% of patients in
clinical studies had their partial-onset seizures reduced by half or more.
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
Anti-Epileptic Medications
Dilantin Tegretol Trileptal Zonegran
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
Banzel (Rufinamide) FDA approved in 2008
Indicated for add on treatment of seizures associated with Lennox-Gastaut 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
Banzel (Rufinamide) reduction in total seizure number 42.5% median percentage reduction
in tonic-atonic seizure (drop attack) significant improvement in seizure
severity
Banzel (Rufinamide)
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.
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
Sabril (Vigabatrin) FDA approved in 2009
Refractory complex partial seizures Infantile spasms (IS) - babies
between the ages of 1 month and 2 years
Infantile spasms
Onset typically 4-8 months infantile spasms developmental regression specific pattern on EEG called
hypsarrhythmia (chaotic brain waves)
Sabril (Vigabatrin) Mechanism of action Preventing breaking down of GABA.
GABA is chemical that suppresses activity in neurons.
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.
Ezogabine (Potiga) Adjunctive therapy in partial-onset
seizures uncontrolled by current medications in adults
FDA approved in 2011 but not available yet in USA
Ezogabine (Potiga)
Novel mechanism of action
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
Other Treatments
DietEpilepsy Surgery
The Ketogenic Diet
A medically prescribed, strict dietary regimen used for the refractory pediatric patient
Ketogenic Diet
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 dietside effects
Dehydration, constipation, kidney stones or gall stones, pancreatitis, decreased bone density, menstrual irregularities.
vitamins have to be added through supplements.
Diet in adults
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
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
Surgical devices Vagus Nerve Stimulator Deep Brain Stimulation Neuropace
Surgical devices Vagus Nerve Stimulator Deep Brain Stimulation Neuropace
Deep Brain stimulation
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
responsive neurostimulator which is implanted in the brain, detects abnormal electrical activity and sends out electrical impulses to prevent seizures
Clinical trials started
THANK YOU!
Northeast Regional Epilepsy Groupepilepsygroup.com