Diagnosis and Treatment of Epilepsy Marcelo E. Lancman, M.D. Director, Epilepsy Program NEREG Comprehensive Epilepsy Center Referrals Evaluation: ●History/Exam ●EEG ●Imaging Controlled Not Controlled Video-EEG Non-epileptic Events Refer Epilepsy Medical Management Surgical Management Epilepsy and Seizures What is epilepsy? What is a seizure? Incidence Epilepsy 0.5-1% Seizures 5-10% Classification Partial Simple Complex Generalized Absence Atonic Clonic Tonic Tonic-clonic Myoclonic Evaluation…A Team Approach Initial intake by epileptologist – Patient/family history – Physical exam – Review of records Plan to include… Testing – EEG, labs Imaging – MRI, CT Diagnosis and Control Diagnosis is clear Patient placed on anti-epileptic drug appropriate for type of epilepsy The Poorly Controlled, Intractable Seizure Patient Despite medical management, patient continues to have frequent, debilitating seizures Commonly on polytherapy (more than one medication) Video-EEG Monitoring Continuous EEG monitoring along with continuous audio-video taping Requires inpatient admission Goals of Video-EEG Monitoring Epilepsy vs. nonepileptic events Characterize epilepsy type Pre-surgical evaluation 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 Non-epileptic events Physiologic (other medical conditions) – Referred to other medical specialist Psychological or pseudoseizures – Referred to psychiatry and neuropsychologist who work with this type of stress-seizure – Psychiatric medication, psychotherapy, education Brief history of epilepsy treatment 1912: phenobarbital 1924: EEG began to be used All of the treatments we will discuss today have only come about in the last 80 years 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 “Old Reliables” Carbamazepine (Tegretol) Phenytoin (Dilantin/Cerebyx) Phenobarbital Valproic acid (Depakote) Ethosuximide (Zarontin) Primidone (Mysoline) Newer AED’s Gabapentin (Neurontin) Tiagabine (Gabitril) Lamotrigine (Lamictal) Pregabalin (Lyrica) Topiramate (Topamax) Zonisamide (Zonegran) Felbamate (Felbatol) Levetiracetam (Keppra) Diastat (Diazepam) Oxcarbazepine (Trileptal) Rufinamide (Banzel) Medication choices based on epilepsy type… AED’s for Partial Epilepsy Tegretol Dilantin Depakote Neurontin Lamictal Phenobarbital Pregabalin Keppra Topamax Gabitril Zonegran Trileptal Mysoline Best AED’s for Generalized Epilepsy Depakote Lamictal Topamax Zonegran Keppra Rufinamide 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 How to use polytherapy rationally Side effects – Dose-related – Idiosyncratic (each person is different) For patients that do not respond to medication Ketogenic diet Vagus nerve stimulator Epilepsy surgery 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 Epilepsy Surgery The goals are: – To determine where the seizures are coming from – To make sure is safe Epilepsy Surgery To determine where the seizures are coming from Video-EEG monitoring MRI MRS: PET: SPECT: EEG Slide Fp1-F7 F7-FT9 FT9-T7 T7-P7 P7-O1 Fp2-F8 F8-FT0 FT0-T8 T8-P8 P8-O2 FT9-FT0 A1-A2 Fp1-F3 F3-C3 C3-P3 P3-O1 Fp2-F4 F4-C4 C4-P4 P4-O2 ECG-RF ECG-RF SaO2(%) 0 0 0 0 0 HR(bpm) 0 0 0 0 Comment 0 spike 0 0 99-10-31/ROUTINE 0 0 0 0 0 0 0 0 Fp1-F7 F7-FT9 FT9-T7 T7-P7 P7-O1 Fp2-F8 F8-FT0 FT0-T8 T8-P8 P8-O2 FT9-FT0 A1-A2 Fp1-F3 F3-C3 C3-P3 P3-O1 Fp2-F4 F4-C4 C4-P4 P4-O2 ECG-RF SaO2(%) 0 0 0 0 0 0 0 0 0 0 HR(bpm) 0 0 0 0 0 0 0 0 0 Comment 0 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 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 Types of Epilepsy Surgery Temporal Lobectomy Extratemporal Resections Hemispherectomy Corpus Callosotomy 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 Complications of surgery Low rate of complications – – – – Infections Bleeding Anesthesia Function 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 Summary Ways to treat epilepsy – – – – Medications Ketogenic Diet Surgery Vagus nerve stimulator Diagnostic Advances Magnetoencefalography Functional MRI Advances in Treatment Newermedications – – – – – – – – – – – – – – Brivaracetam Carisbamate Clobazam Eslicarbazepine Ganaxalone Losigamone Nitrfazepam Perampanel Piracetam Progabide Remacemide Retigabine Seletracetam Stiripentol Deep Brain Stimulation (DBS) Neuropace Alternative Treatments Diets Supplements Herbs Oxygen therapy Relaxation techniques – Neurofeedback – Art therapy – Massage/yoga Herbs that have been used or reported to help control seizures Aloe Vera (Aloe Barbadenis) Black Cohosh (Cimicifuga racemosa) Black pepper (piper nigrum) Blue vervarian (Verbena hastate) Borage (borago officinalis) Buplerum (Blupleurum chinense) Burning bush (Dictamnus albus) Calotropis (Calotropis gigantea) Carline thistle (Carline thistle) Chamomile (matricaria recutita) Chinaberry juice (azadirachta indica) Herbs that have been used or reported to help control seizures Chrysanthemum (Chrysanthemum morifolium) Elderberry (Sambucus nigra) European Peony (Paeonia lactiflora) Flax seed oil (Linum usitatissimum) Forskolin (Coleus forskohlii) Geranium (Geranium dioxide) Ginger (Zingiber officinale) Ginkgo Biloba (Ginkgo Biloba) Ginseng (Panax quinquefolius) Gotu Kola (Centella asiatica) Groundsel (Senecio vulgaris) Hyssop (Hyssopus officinalis) Herbs that have been used or reported to help control seizures Kava (piper methysticum) Lady’s slipper (Cypripedium pubescens) Lobelia (Lobelia inflata) Marijuana (cannabis) Mistletoe (viscum album) Mugwort (Artemisia vulgaris) Passion flower (passiflora incarnata) Pipsissewa (chimaphila umbellate) Skullcap (scutellaria galericulata) Tree of Heaven (Ailanthus altissima) Valerian (valeriana oficinalis) Vervain (Verbena officinalis) Withania (withania sominfera) Yarrow (achillea millefolium) Yew (taxus bacatta) Herbs that are reported to cause seizures American hellebore Bearberry (arcostaphyllus uva-ursi) Borage (Borago ifficinalis) Ephedra (ephedra) Essential oils Evening primrose (oenothera biennis) Gingko (gingko) Ginseng (Panax quinquefolius) Hyssop (Hyssopus officinalis) Ma Huang (herba ephedra) Mistletoe (viscum album) Monkshood (aconilum) Primrose (Oenothera biennis) Skullcap (scutellaria galericulata) Yew (taxus bacatta) Yohimbe (pausinystalta yohimbe) Herbs that can affect seizure medications Aloe Vera (Aloe Barbadenis) American hellebore Chamomile (matricaria recutita) Echinacea (Echinacea purpurea) Garlic (allium sativum) Ginkgo biloba Gotu Kola (Centella asiatica) Kava (piper methysticum) Licorice (Glycyrrhiza glabra) Milk thistle (silybum marianum) Mistletoe (viscum album) Mugwort (Artemisia vulgaris) Passion flower (passiflora incarnata) Pipsissewa (chimaphila umbellate) Pycnogel (pinus maritime) Red clover (trifolium pretense) St John’s wort (hypericum perforatum) Valerian (valeriana oficinalis)