Advances in the Diagnosis and Treatment of Epilepsy

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

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

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 • EEG, AEEG, VEEG • Labs • Genetics • Imaging • 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

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

30. 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) Newer AED’s

31. Medication choices based on epilepsy type…

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

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

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

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

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