Advances in the Treatment of Epilepsy Olgica Laban-Grant, MD 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 seizures 5-10% 0.5-2% Seizure vs. Epilepsy Single seizure Recurrent seizures 5-10% 0.5-2%

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 Therapy Trial and Error Method Epilepsy Time First AED Increase Dosage Switch AED Combine AEDs Polytherapy Trial and Error Method 17

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. 18

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

Partial (Focal) Seizures Generalized Seizures 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 Diet Epilepsy 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 diet side 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 Group epilepsygroup.com