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

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

18. Response to AEDs PharMetrics. April 2002 to June 2003
IMS NPA, Dec 2003.
Kwan P, Brodie MJ. N Engl J Med 2000; 342: 18

19. Combine medications with different mechanism of action

20. 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)

21. 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)

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 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

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. Other Treatments
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 diet side effects
Dehydration, constipation, kidney stones or gall stones, pancreatitis, decreased bone density, menstrual irregularities.
vitamins have to be added through supplements.

51. 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.

52. 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

53. 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

54. Surgical devices Vagus Nerve Stimulator Deep Brain Stimulation
Neuropace

55. Surgical devices Vagus Nerve Stimulator Deep Brain Stimulation
Neuropace

56. 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

57. Neuropace
responsive neurostimulator which is implanted in the brain, detects abnormal electrical activity and sends out electrical impulses to prevent seizures
Clinical trials started

58. THANK YOU!
Northeast Regional Epilepsy Group
epilepsygroup.com