1. Advances in the Diagnosis and Treatment of Epilepsy
Marcelo E. Lancman, M.D.
Director, Epilepsy Program
Northeast Regional Epilepsy Group

2. Advances in the Diagnosis and Treatment of Epilepsy
Epilepsy concepts
Diagnosing Epilepsy
What causes Epilepsy
Treating Epilepsy
New developments

3. Epilepsy Concepts
What is epilepsy?
What is a seizure?

4. Incidence
Epilepsy
0.5-1%
Seizures
5-10%

5. Classification of Seizures
Partial
Simple
Complex
Secondary Generalized
Generalized
Absence
Atonic
Clonic
Tonic
Tonic-clonic
Myoclonic

6. Classification of Epilepsy
By Localization
Partial
Generalized
By Cause
Idiopathic (unknown)
Symptomatic

7. Classification of Epilepsy
Idiopathic Partial Epilepsy
Symptomatic Partial Epilepsy
Idiopathic Generalized Epilepsy
Symptomatic Generalized Epilepsy

8. Idiopathic Generalized Epilepsy
Benign Neonatal Familial Epilepsy
Benign Myoclonic Epilepsy of Infancy
Generalized epilepsy with febrile seizures plus
Epilepsy with myoclonic absence
Epilepsy with myoclonic-astatic seizures
Childhood absence epilepsy
Juvenile absence epilepsy
Epilepsy with GTCS only

9. Idiopathic Partial Epilepsy
Benign Rolandic Epilepsy
Benign Occipital Epilepsy

10. Symptomatic Generalized Epilepsy
Infantile spasms (West syndrome)
Dravet syndrome
Lennox-Gastaut syndrome

11. Symptomatic Partial Epilepsy
Temporal Lobe Epilepsy
Frontal Lobe Epilepsy
Parietal Lobe Epilepsy
Occipital Lobe Epilepsy

12. Type of Epilepsy
The importance of knowing

13. Diagnosis of Epilepsy
Medical History
Physical exam

14. Testing Testing Imaging EEG, AEEG, VEEG Labs Genetics
CT, MRI (high definition)

15. Diagnosis Diagnosis is clear: treatment is initiated
Diagnosis unclear: Video-EEG

16. Video-EEG Monitoring
Continuous EEG monitoring along with continuous audio-video recording
Mostly requires inpatient admission

17. Goals of Video-EEG Monitoring
Epilepsy vs. non-epileptic events
Characterize epilepsy type
Pre-surgical evaluation

18. Non-Epileptic Events
20 to 30% of patients referred with diagnosis of intractable epilepsy
Events that do not have electrical source in brain
May have physical or psychological causes that are not epilepsy
But CAN also occur in patients who have epilepsy

19. Non-epileptic events Physiologic (other medical conditions)
Fainting, low sugar, changes in electrolytes, toxins, fever.
Psychological
Referred to psychiatry and neuropsychologist who work with this type of stress-seizure
Psychiatric medication, psychotherapy, education

20. Non-epileptic events Conditions that may look like seizures:
TIAs, complicated migraines, movement disorders, sleep disorders, anxiety/panic disorder, vertigo, cardiac disorders, rage attacks, breath-holding spells,

21. What causes of Epilepsy?
The seizure threshold
Causes:
Genetics, head injury, stroke, tumors, infections, malformations, metabolic disorders (diabetes, thyroid, parathyroid, adrenal), degenerative disorders, perinatal factors and other less common (cardiac, GI, blood, inflammatory, poisons, etc)

22. Seizure Triggers
Alcohol, stress, environmental temperature, lights, fever/illness, hormonal changes, hyperventilation, sleep deprivation, medications and supplements, missing medication doses and travel across time zones

23. Treating Epilepsy What is intractable epilepsy?
Despite medical management, patient continues to have frequent, debilitating seizures

24. Seizure Control
I discussed on the earlier slide drug resistant epilepsy, or seizures that are hard to controll with medicine, puts a person at higher risk for SUDEP. About 1/3 of people with epilepsy have drug resistant epilepsy. The definition of DRE is where seizures keep occuring despite 2 good trials of seizure medication. A good trial of a seizue medication means that an appropriate medication was used for the patient’s epilepsy and an appropriate dose was achieved. The medication failed because of persistent seizures and not side effects. For example, if the patient was still in the procress of increasing the medication to the target dose, and then had to stop it because of side effects, we wouldn’t call this a drug failure.
Also, there are many types of epilepsy, and not all doctors specialize in epilepsy. Different medications work for each type of epilepsy. Sometimes doctors, despite their best intentions, prescribe the wrong seizure medication for a patient’s epilepsy. For example, tegretol for absence seizures, which can make it worse.
So, a patient is only drug resistant only if they have tried two or more appropriate medications for their epilepsy and failed them because of persistent seizures.

25. Options for the Intractable Seizure Patient
Medications (combinations)
Diets
Surgical procedures
Stimulators
Resections

26. Medications
Choices based on epilepsy type, patient profile, side effect profile, cost
Best to have patient on single antiepileptic drug (AED)
May need polytherapy (combination of medications)
Adding meds requires going up slowly with the new agent before discontinuing previous drug
Polytherapy requires deep knowledge of interactions

27. How to use polytherapy rationally
Pharmacodynamics (what the medication does to the body)
Pharmacokinetics
(what the body does to the medications)
Absorption
Distribution
Elimination
Half life
Liver
Kidneys

28. How to use polytherapy rationally
Side effects
Dose-related
Idiosyncratic (each person is different)

29. Older Medications Carbamazepine (Tegretol) Phenobarbital
Ethosuximide (Zarontin)
Phenytoin (Dilantin/Cerebyx)
Valproic acid (Depakote)
Primidone (Mysoline)

30. Newer AED’s Gabapentin (Neurontin) Lamotrigine (Lamictal)
Topiramate (Topamax)
Felbamate (Felbatol)
Diastat (Diazepam)
Vigabatrin (Sabril)
Ezogabine (Potiga)
Oxcarbazepine (Trileptal)
Pregabalin (Lyrica)
Zonisamide (Zonegran)
Levetiracetam (Keppra)
Lacosamide (Vimpat)
Rufinamide (Banzel)
Clobazam (Onfi)

31. Medication choices based on epilepsy type…

32. AED’s for Partial Epilepsy
All but Zarontin and Banzel

33. Best AED’s for Generalized Epilepsy
Depakote
Keppra
Lamictal
Topamax
Zonegran
Banzel

34. Future Medications Brivaracetam Carisbamate Eslicarbazepine Ganaxalone
Losigamone
Nitrfazepam
Perampanel
Piracetam
Progabide
Remacemide
Retigabine
Seletracetam
Stiripentol

35. What Are Some Promising New Medical Treatments?
Maintenance Treatment
Ezogabine (Potiga)
Perampanel
Vertex
Emergency Treatment
Intranasal Midazolam

36. Potiga Potassium Channel Opener Partial Seizures
Rare but serious side effects
Trial and Error: Every pt is different. We don’t now until we try which will be the right receptors to open and right ones to block
Side effects: when you block too many neurotransmitters, channels- you disturb normal brain function and you get side effect. For example if too many NT are blocked you get sleepy and dizzy
1/3: New medication are not any better than old

37. Peramapanel Glutamate Blocker Effective in trials for partial seizures
Side effects: Dizziness, Sleepiness
Approved in Europe
Under study in US for Generalized Seizure types
Under FDA review for Partial Seizures

38. Vx-765 for Partial Epilepsy
New approach to Epilepsy Rx
Anti-Inflammatory
Short Duration of therapy (weeks instead of years)
Oral Medicine
Early Clinical Trials Completed
Early results encouraging but longer treatment duration to be studied
Headache, dizziness, GI most common side effects
Only studied for 6 weeks

39. Emergency Treatment Rectal Diastat Clinically proven Hard to give
Adults don’t like
Can’t self administer

40. Intranasal Midazolam Easy to give Preferred route
Can be self-administered or given by caretaker
Under study
Efficacy and Side Effects unknown

41. Advances in Treatment Newermedications Brivaracetam Carisbamate
Clobazam
Eslicarbazepine
Ganaxalone
Losigamone
Nitrfazepam
Perampanel
Piracetam
Progabide
Remacemide
Retigabine
Seletracetam
Stiripentol

42. For patients that do not respond to medication
Ketogenic diet
Surgeries

43. Ketogenic Diet (@1920) High fat, low carbohydrate/protein diet
Requires hospitalization to start it
NPO until patient in ketosis
Parent education
Meds to be taken into account
Recommended mainly for young children due to compliance and efficacy

44. Epilepsy Surgery The goals are:
To determine where the seizures are coming from
To make sure is safe

45. Epilepsy Surgery To determine where the seizures are coming from
Video-EEG monitoring
MRI
MRS:
PET:
SPECT:
MEG:

46. Epilepsy Surgery To make sure that it is safe
Wada test: to study speech and memory
Neuropsychological testing: mental functions (IQ, memory, attention) and personality assessment
Psychological evaluation
Ophthalmologic evaluation

47. Epilepsy Surgery
Some cases in which the localization is not clear or where function could be affected will require INVASIVE ELECTRODES
Depth electrodes
Subdural electrodes

48. Types of Epilepsy Surgery
Temporal Lobectomy
Extratemporal Resections
Hemispherectomy
Corpus Callosotomy

49. Outcome after epilepsy surgery
Anterior temporal lobectomy
70-80% seizure free
Neocortical resection
With lesion: 50-80% seizure free
Without lesion: 30-50% seizure free
Hemispherectomy
Significant improvement
Corpus Callosotomy
Significant improvement for drop attacks

50. Complications of surgery
Low rate of complications
Infections
Bleeding
Anesthesia
Function

51. Vagus Nerve Stimulator (1997)
Intractable epilepsy patient without focus or desires interim step before epilepsy surgery
Goal is to reduce amount/severity of seizures vs. cure
Device surgically implanted in left chest/axilla area
Coils around left vagus nerve
Stimulation is automatic; patient can additionally stimulate device if aura