1. Diagnosis and Treatment of Epilepsy Marcelo E. Lancman, M.D. Director, Epilepsy Program NEREG

2. Referrals Comprehensive Epilepsy Center Evaluation: ●History/Exam ●EEG ●Imaging Controlled Not Controlled Video-EEG Non-epileptic Events Epilepsy Medical Management Surgical Management Refer

3. Epilepsy and Seizures What is epilepsy? What is epilepsy? What is a seizure? What is a seizure?

4. Incidence Epilepsy Epilepsy0.5-1% Seizures Seizures 5-10%

5. Classification Partial PartialSimpleComplex Generalized Generalized Absence Atonic Clonic Tonic Tonic-clonic Myoclonic

6. Evaluation…A Team Approach Initial intake by epileptologist Initial intake by epileptologist –Patient/family history –Physical exam –Review of records

7. Plan to include… Testing Testing –EEG, labs Imaging Imaging –MRI, CT

9. Diagnosis and Control Diagnosis is clear Diagnosis is clear Patient placed on anti-epileptic drug appropriate for type of epilepsy Patient placed on anti-epileptic drug appropriate for type of epilepsy

10. The Poorly Controlled, Intractable Seizure Patient Despite medical management, patient continues to have frequent, debilitating seizures Despite medical management, patient continues to have frequent, debilitating seizures Commonly on polytherapy (more than one medication) Commonly on polytherapy (more than one medication)

11. Video-EEG Monitoring Continuous EEG monitoring along with continuous audio-video taping Continuous EEG monitoring along with continuous audio-video taping Requires inpatient admission Requires inpatient admission

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

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

14. Non-epileptic events Physiologic (other medical conditions) Physiologic (other medical conditions) –Referred to other medical specialist Psychological or pseudoseizures Psychological or pseudoseizures –Referred to psychiatry and neuropsychologist who work with this type of stress-seizure –Psychiatric medication, psychotherapy, education

15. Brief history of epilepsy treatment 1912: phenobarbital 1912: phenobarbital 1924: EEG began to be used 1924: EEG began to be used All of the treatments we will discuss today have only come about in the last 80 years All of the treatments we will discuss today have only come about in the last 80 years

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

17. “Old Reliables” Carbamazepine (Tegretol) Carbamazepine (Tegretol) Phenobarbital Phenobarbital Ethosuximide (Zarontin) Ethosuximide (Zarontin) Phenytoin (Dilantin/Cerebyx) Phenytoin (Dilantin/Cerebyx) Valproic acid (Depakote) Valproic acid (Depakote) Primidone (Mysoline) Primidone (Mysoline)

18. Newer AED’s Gabapentin (Neurontin) Gabapentin (Neurontin) Lamotrigine (Lamictal) Lamotrigine (Lamictal) Topiramate (Topamax) Topiramate (Topamax) Felbamate (Felbatol) Felbamate (Felbatol) Diastat (Diazepam) Diastat (Diazepam) Tiagabine (Gabitril) Tiagabine (Gabitril) Pregabalin (Lyrica) Pregabalin (Lyrica) Zonisamide (Zonegran) Zonisamide (Zonegran) Levetiracetam (Keppra) Levetiracetam (Keppra) Oxcarbazepine (Trileptal) Oxcarbazepine (Trileptal) Rufinamide (Banzel) Rufinamide (Banzel)

19. Medication choices based on epilepsy type…

20. AED’s for Partial Epilepsy Tegretol Tegretol Dilantin Dilantin Depakote Depakote Neurontin Neurontin Lamictal Lamictal Phenobarbital Phenobarbital Pregabalin Pregabalin Keppra Keppra Topamax Topamax Gabitril Gabitril Zonegran Zonegran Trileptal Trileptal Mysoline Mysoline

21. Best AED’s for Generalized Epilepsy Depakote Depakote Lamictal Lamictal Topamax Topamax Zonegran Zonegran Keppra Keppra Rufinamide Rufinamide

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

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

24. For patients that do not respond to medication Ketogenic diet Ketogenic diet Vagus nerve stimulator Vagus nerve stimulator Epilepsy surgery Epilepsy surgery

25. Ketogenic Diet (@1920) High fat, low carbohydrate/protein diet High fat, low carbohydrate/protein diet Requires hospitalization to start it 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 Recommended mainly for young children due to compliance and efficacy

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

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

28. EEG Slide 99-10-31/ROUTINE

33. Epilepsy Surgery To make sure that it is safe 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

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

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

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

41. Complications of surgery Low rate of complications Low rate of complications –Infections –Bleeding –Anesthesia –Function

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

44. Summary Ways to treat epilepsy Ways to treat epilepsy –Medications –Ketogenic Diet –Surgery –Vagus nerve stimulator

45. Diagnostic Advances Magnetoencefalography Magnetoencefalography

46. Functional MRI Functional MRI

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

48. Deep Brain Stimulation (DBS)

49. Neuropace Neuropace

50. Alternative Treatments Diets Diets Supplements Supplements Herbs Herbs Oxygen therapy Oxygen therapy Relaxation techniques Relaxation techniques –Neurofeedback –Art therapy –Massage/yoga

51. Herbs that have been used or reported to help control seizures Aloe Vera (Aloe Barbadenis) Aloe Vera (Aloe Barbadenis) Black Cohosh (Cimicifuga racemosa) Black Cohosh (Cimicifuga racemosa) Black pepper (piper nigrum) Black pepper (piper nigrum) Blue vervarian (Verbena hastate) Blue vervarian (Verbena hastate) Borage (borago officinalis) Borage (borago officinalis) Buplerum (Blupleurum chinense) Buplerum (Blupleurum chinense) Burning bush (Dictamnus albus) Burning bush (Dictamnus albus) Calotropis (Calotropis gigantea) Calotropis (Calotropis gigantea) Carline thistle (Carline thistle) Carline thistle (Carline thistle) Chamomile (matricaria recutita) Chamomile (matricaria recutita) Chinaberry juice (azadirachta indica) Chinaberry juice (azadirachta indica)

52. Herbs that have been used or reported to help control seizures Chrysanthemum (Chrysanthemum morifolium) Chrysanthemum (Chrysanthemum morifolium) Elderberry (Sambucus nigra) Elderberry (Sambucus nigra) European Peony (Paeonia lactiflora) European Peony (Paeonia lactiflora) Flax seed oil (Linum usitatissimum) Flax seed oil (Linum usitatissimum) Forskolin (Coleus forskohlii) Forskolin (Coleus forskohlii) Geranium (Geranium dioxide) Geranium (Geranium dioxide) Ginger (Zingiber officinale) Ginger (Zingiber officinale) Ginkgo Biloba (Ginkgo Biloba) Ginkgo Biloba (Ginkgo Biloba) Ginseng (Panax quinquefolius) Ginseng (Panax quinquefolius) Gotu Kola (Centella asiatica) Gotu Kola (Centella asiatica) Groundsel (Senecio vulgaris) Groundsel (Senecio vulgaris) Hyssop (Hyssopus officinalis) Hyssop (Hyssopus officinalis)

53. Herbs that have been used or reported to help control seizures Kava (piper methysticum) Kava (piper methysticum) Lady’s slipper (Cypripedium pubescens) Lady’s slipper (Cypripedium pubescens) Lobelia (Lobelia inflata) Lobelia (Lobelia inflata) Marijuana (cannabis) Marijuana (cannabis) Mistletoe (viscum album) Mistletoe (viscum album) Mugwort (Artemisia vulgaris) Mugwort (Artemisia vulgaris) Passion flower (passiflora incarnata) Passion flower (passiflora incarnata) Pipsissewa (chimaphila umbellate) Pipsissewa (chimaphila umbellate) Skullcap (scutellaria galericulata) Skullcap (scutellaria galericulata) Tree of Heaven (Ailanthus altissima) Tree of Heaven (Ailanthus altissima) Valerian (valeriana oficinalis) Valerian (valeriana oficinalis) Vervain (Verbena officinalis) Vervain (Verbena officinalis) Withania (withania sominfera) Withania (withania sominfera) Yarrow (achillea millefolium) Yarrow (achillea millefolium) Yew (taxus bacatta) Yew (taxus bacatta)

54. Herbs that are reported to cause seizures American hellebore American hellebore Bearberry (arcostaphyllus uva-ursi) Bearberry (arcostaphyllus uva-ursi) Borage (Borago ifficinalis) Borage (Borago ifficinalis) Ephedra (ephedra) Ephedra (ephedra) Essential oils Essential oils Evening primrose (oenothera biennis) Evening primrose (oenothera biennis) Gingko (gingko) Gingko (gingko) Ginseng (Panax quinquefolius) Ginseng (Panax quinquefolius) Hyssop (Hyssopus officinalis) Hyssop (Hyssopus officinalis) Ma Huang (herba ephedra) Ma Huang (herba ephedra) Mistletoe (viscum album) Mistletoe (viscum album) Monkshood (aconilum) Monkshood (aconilum) Primrose (Oenothera biennis) Primrose (Oenothera biennis) Skullcap (scutellaria galericulata) Skullcap (scutellaria galericulata) Yew (taxus bacatta) Yew (taxus bacatta) Yohimbe (pausinystalta yohimbe) Yohimbe (pausinystalta yohimbe)

55. Herbs that can affect seizure medications Aloe Vera (Aloe Barbadenis) Aloe Vera (Aloe Barbadenis) American hellebore American hellebore Chamomile (matricaria recutita) Chamomile (matricaria recutita) Echinacea (Echinacea purpurea) Echinacea (Echinacea purpurea) Garlic (allium sativum) Garlic (allium sativum) Ginkgo biloba Ginkgo biloba Gotu Kola (Centella asiatica) Gotu Kola (Centella asiatica) Kava (piper methysticum) Kava (piper methysticum) Licorice (Glycyrrhiza glabra) Licorice (Glycyrrhiza glabra) Milk thistle (silybum marianum) Milk thistle (silybum marianum) Mistletoe (viscum album) Mistletoe (viscum album) Mugwort (Artemisia vulgaris) Mugwort (Artemisia vulgaris) Passion flower (passiflora incarnata) Passion flower (passiflora incarnata) Pipsissewa (chimaphila umbellate) Pipsissewa (chimaphila umbellate) Pycnogel (pinus maritime) Pycnogel (pinus maritime) Red clover (trifolium pretense) Red clover (trifolium pretense) St John’s wort (hypericum perforatum) St John’s wort (hypericum perforatum) Valerian (valeriana oficinalis) Valerian (valeriana oficinalis)