Advances in the Treatment of Epilepsy

1
Advances in theTreatment 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

5
(No Transcript)
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
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
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
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

27
(No Transcript)
28
Anti-Epileptic Medications
29

• Dilantin
• Tegretol
• Trileptal
• Zonegran

30

• Vimpat

31
Lacosamide(Vimpat)
32
Lacosamide (Vimpat)

• Side effects
• Depression 1500
• 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 1500
• 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 dietside 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