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

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Presentation on theme: "Advances in the Diagnosis and Treatment of Epilepsy Marcelo E. Lancman, M.D. Director, Epilepsy Program Northeast Regional Epilepsy Group."— Presentation transcript:

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

3 Epilepsy Concepts 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 of Seizures Partial PartialSimpleComplex Secondary Generalized Generalized Generalized Absence Atonic Clonic Tonic Tonic-clonic Myoclonic

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

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

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

9 Idiopathic Partial Epilepsy Benign Rolandic Epilepsy Benign Rolandic Epilepsy Benign Occipital Epilepsy Benign Occipital Epilepsy

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

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

12 Type of Epilepsy The importance of knowing The importance of knowing

13 Diagnosis of Epilepsy Medical History Medical History Physical exam Physical exam

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

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

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

17 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

18 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

19 Non-epileptic events Physiologic (other medical conditions) Physiologic (other medical conditions) –Fainting, low sugar, changes in electrolytes, toxins, fever. Psychological 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: 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 The seizure threshold Causes: 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 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? 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) Medications (combinations) Diets Diets Surgical procedures Surgical procedures –Stimulators –Resections

26 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

27 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

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

29 Older Medications 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)

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

31 Medication choices based on epilepsy type…

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

33 Best AED’s for Generalized Epilepsy Depakote Depakote Keppra Keppra Lamictal Lamictal Topamax Topamax Zonegran Zonegran Banzel 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 Maintenance Treatment –Ezogabine (Potiga) –Perampanel –Vertex Emergency Treatment Emergency Treatment –Intranasal Midazolam

36 Potiga Potassium Channel Opener Potassium Channel Opener Partial Seizures Partial Seizures Rare but serious side effects Rare but serious side effects

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

38 Vx-765 for Partial Epilepsy New approach to Epilepsy Rx New approach to Epilepsy Rx –Anti-Inflammatory –Short Duration of therapy (weeks instead of years) –Oral Medicine Early Clinical Trials Completed 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 Rectal Diastat –Clinically proven –Hard to give –Adults don’t like –Can’t self administer

40 Intranasal Midazolam Easy to give Easy to give Preferred route Preferred route Can be self- administered or given by caretaker Can be self- administered or given by caretaker Under study Under study

41 Advances in Treatment Newermedications 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 Ketogenic diet Surgeries Surgeries

43 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

44 Epilepsy Surgery The goals are: 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 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 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 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 Temporal Lobectomy Extratemporal Resections Extratemporal Resections Hemispherectomy Hemispherectomy Corpus Callosotomy Corpus Callosotomy

49 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

50 Complications of surgery Low rate of complications 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 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


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