Advances in the Treatment of Epilepsy

1. Advances in theTreatment of Epilepsy OlgicaLaban-Grant, MD Northeast Regional Epilepsy Group epilepsygroup.com

2. 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

3. 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

4. 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

6. Anti-Epileptic Medications

7. 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.

8. 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.

9. Seizure vs. Epilepsy Single seizure Recurrent seizures 5-10% 0.5-2%

10. Why EEG • EEG as predictor of the risk of recurrence within two years of first seizure • epileptic discharges - 83% • nonepileptic abnormalities -41% • Normal – 12%

11. Epilepsy • Epilepsy is a tremendously variable condition in terms of its cause, seizure types and response to treatment.

12. Trteatment • Depends on many factors: • Age • Type of seizures • Type of epilepsy • Medical history • Frequency and severity of seizures • Available drug formulations of medications

13. Treating Epilepsy The goal in treating epilepsy is No seizures No side effects

14. Treating Epilepsy • First line treatment is medication • Surgery and surgical devices • Diet • Lifestyle (avoiding trigger factors)

15. Medications • Medications do not cure epilepsy, rather they control epilepsy by suppressing the seizures.

16. 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.

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

18. 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.

19. Combine medications with different mechanism of action

20. 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

21. 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) Anti-Epileptic Medications

22. 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

23. Partial (Focal) Seizures Simple Partial Complex Partial Generalized Seizures Absence Myoclonic Clonic Tonic Tonic-Clonic Atonic International League Against Epilepsy (ILEA)Classification of Seizures

24. Partial Seizures • Simple Partial: No impairment of consciousness. • Complex Partial: Altered awareness

25. Lacosamide (Vimpat) Approximately 40% of patients in clinical studies had their partial-onset seizures reduced by half or more. More seizure-free days

26. 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

28. Anti-Epileptic Medications

29. Dilantin • Tegretol • Trileptal • Zonegran

30. Vimpat

31. Lacosamide(Vimpat)

32. 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

33. 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.

34. 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

35. Banzel (Rufinamide) reduction in total seizure number 42.5% median percentage reduction in tonic-atonic seizure (drop attack) significant improvement in seizure severity

36. 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)

37. 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.

38. 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

39. Sabril (Vigabatrin) FDA approved in 2009 Refractory complex partial seizures Infantile spasms (IS) - babies between the ages of 1 month and 2 years

40. Infantile spasms Onset typically 4-8 months infantile spasms developmental regression specific pattern on EEG called hypsarrhythmia (chaotic brain waves)

41. Sabril (Vigabatrin) Mechanism of action Preventing breaking down of GABA. GABA is chemical that suppresses activity in neurons.

42. Anti-Epileptic Medications

43. 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.

44. Ezogabine (Potiga) Adjunctive therapy in partial-onset seizures uncontrolled by current medications in adults FDA approved in 2011 but not available yet in USA

45. Ezogabine (Potiga) Novel mechanism of action Potassium channel opener

46. Ezogabine (Potiga) Side effects dizziness, fatigue, tremor, problems with coordination, double vision memory impairment lack of strength. urinary retention confusion, hallucinations depression

47. OtherTreatments Diet Epilepsy Surgery

48. The Ketogenic Diet A medically prescribed, strict dietary regimen used for the refractory pediatric patient

49. 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

50. The Ketogenic dietside effects • Dehydration, constipation, kidney stones or gall stones, pancreatitis, decreased bone density, menstrual irregularities. • vitamins have to be added through supplements.