Advances in the Diagnosis and Advances in the Diagnosis and Treatment of Epilepsy Treatment of Epilepsy

Marcelo E. Lancman, M.D.Marcelo E. Lancman, M.D.Director, Epilepsy ProgramDirector, Epilepsy Program

Northeast Regional Epilepsy GroupNortheast Regional Epilepsy Group

Advances in the Diagnosis Advances in the Diagnosis and Treatment of Epilepsy and Treatment of Epilepsy Epilepsy conceptsEpilepsy concepts Diagnosing EpilepsyDiagnosing Epilepsy What causes EpilepsyWhat causes Epilepsy Treating EpilepsyTreating Epilepsy New developmentsNew developments

Epilepsy ConceptsEpilepsy Concepts

What is epilepsy?What is epilepsy?

What is a seizure?What is a seizure?

IncidenceIncidence

EpilepsyEpilepsy

0.5-1% 0.5-1%

SeizuresSeizures

5-10%5-10%

Classification of SeizuresClassification of Seizures

PartialPartialSimpleSimple

ComplexComplex

Secondary GeneralizedSecondary Generalized

GeneralizedGeneralizedAbsenceAbsence

AtonicAtonic

ClonicClonic

TonicTonic

Tonic-clonicTonic-clonic

MyoclonicMyoclonic

Classification of EpilepsyClassification of Epilepsy

By LocalizationBy Localization– PartialPartial– GeneralizedGeneralized

By CauseBy Cause– Idiopathic (unknown)Idiopathic (unknown)– SymptomaticSymptomatic

Classification of EpilepsyClassification of Epilepsy

Idiopathic Partial EpilepsyIdiopathic Partial Epilepsy Symptomatic Partial EpilepsySymptomatic Partial Epilepsy Idiopathic Generalized EpilepsyIdiopathic Generalized Epilepsy Symptomatic Generalized EpilepsySymptomatic Generalized Epilepsy

Idiopathic Generalized Idiopathic Generalized EpilepsyEpilepsy Benign Neonatal Familial EpilepsyBenign Neonatal Familial Epilepsy Benign Myoclonic Epilepsy of InfancyBenign Myoclonic Epilepsy of Infancy Generalized epilepsy with febrile seizures plusGeneralized epilepsy with febrile seizures plus Epilepsy with myoclonic absenceEpilepsy with myoclonic absence Epilepsy with myoclonic-astatic seizuresEpilepsy with myoclonic-astatic seizures Childhood absence epilepsyChildhood absence epilepsy Juvenile absence epilepsyJuvenile absence epilepsy Epilepsy with GTCS onlyEpilepsy with GTCS only

Idiopathic Partial EpilepsyIdiopathic Partial Epilepsy

Benign Rolandic EpilepsyBenign Rolandic Epilepsy Benign Occipital EpilepsyBenign Occipital Epilepsy

Symptomatic Generalized Symptomatic Generalized EpilepsyEpilepsy Infantile spasms (West syndrome)Infantile spasms (West syndrome) Dravet syndromeDravet syndrome Lennox-Gastaut syndromeLennox-Gastaut syndrome

Symptomatic Partial EpilepsySymptomatic Partial Epilepsy

Temporal Lobe EpilepsyTemporal Lobe Epilepsy Frontal Lobe EpilepsyFrontal Lobe Epilepsy Parietal Lobe EpilepsyParietal Lobe Epilepsy Occipital Lobe EpilepsyOccipital Lobe Epilepsy

Type of EpilepsyType of Epilepsy

The importance of knowingThe importance of knowing

Diagnosis of EpilepsyDiagnosis of Epilepsy

Medical HistoryMedical History Physical examPhysical exam

TestingTesting

Testing Testing – EEG, AEEG, VEEGEEG, AEEG, VEEG

– LabsLabs

– GeneticsGenetics ImagingImaging

– CT, MRI (high CT, MRI (high definition)definition)

Diagnosis Diagnosis

Diagnosis is clear: treatment is initiatedDiagnosis is clear: treatment is initiated

Diagnosis unclear: Video-EEGDiagnosis unclear: Video-EEG

Video-EEG MonitoringVideo-EEG Monitoring

Continuous EEG monitoring along with Continuous EEG monitoring along with continuous audio-video recordingcontinuous audio-video recording

Mostly requires inpatient admissionMostly requires inpatient admission

Goals of Video-EEG Goals of Video-EEG MonitoringMonitoring Epilepsy vs. non-Epilepsy vs. non-

epileptic eventsepileptic events

Characterize epilepsy Characterize epilepsy typetype

Pre-surgical Pre-surgical evaluation evaluation

Non-Epileptic Events Non-Epileptic Events

20 to 30% of patients referred with 20 to 30% of patients referred with diagnosis of intractable epilepsydiagnosis of intractable epilepsy

Events that do not have electrical source in Events that do not have electrical source in brainbrain

May have physical or psychological May have physical or psychological causes that are not epilepsycauses that are not epilepsy

But CAN also occur in patients who have But CAN also occur in patients who have epilepsyepilepsy

Non-epileptic eventsNon-epileptic events

Physiologic (other medical conditions)Physiologic (other medical conditions)– Fainting, low sugar, changes in electrolytes, Fainting, low sugar, changes in electrolytes,

toxins, fever.toxins, fever. Psychological Psychological

– Referred to psychiatry and neuropsychologist Referred to psychiatry and neuropsychologist who work with this type of stress-seizurewho work with this type of stress-seizure

– Psychiatric medication, psychotherapy, Psychiatric medication, psychotherapy, educationeducation

Non-epileptic eventsNon-epileptic events

Conditions that may look like seizures:Conditions that may look like seizures:– TIAs, complicated migraines, movement TIAs, complicated migraines, movement

disorders, sleep disorders, anxiety/panic disorders, sleep disorders, anxiety/panic disorder, vertigo, cardiac disorders, rage disorder, vertigo, cardiac disorders, rage attacks, breath-holding spells, attacks, breath-holding spells,

What causes of Epilepsy?What causes of Epilepsy?

The seizure thresholdThe seizure threshold Causes:Causes:

– Genetics, head injury, stroke, tumors, Genetics, head injury, stroke, tumors, infections, malformations, metabolic infections, malformations, metabolic disorders (diabetes, thyroid, parathyroid, disorders (diabetes, thyroid, parathyroid, adrenal), degenerative disorders, perinatal adrenal), degenerative disorders, perinatal factors and other less common (cardiac, GI, factors and other less common (cardiac, GI, blood, inflammatory, poisons, etc)blood, inflammatory, poisons, etc)

Seizure TriggersSeizure Triggers

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

Treating EpilepsyTreating Epilepsy

What is intractable epilepsy?What is intractable epilepsy?

Despite medical management, patient Despite medical management, patient continues to have frequent, debilitating continues to have frequent, debilitating seizuresseizures

Seizure ControlSeizure Control

Options for the Intractable Options for the Intractable Seizure PatientSeizure Patient

Medications (combinations)Medications (combinations) DietsDiets Surgical proceduresSurgical procedures

– StimulatorsStimulators– ResectionsResections

MedicationsMedications

Choices based on epilepsy type, patient profile, side Choices based on epilepsy type, patient profile, side effect profile, costeffect 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 Adding meds requires going up slowly with the new agent before discontinuing previous drugagent before discontinuing previous drug

Polytherapy requires deep knowledge of interactionsPolytherapy requires deep knowledge of interactions

How to use polytherapy How to use polytherapy rationallyrationally Pharmacodynamics Pharmacodynamics

(what the medication does to the body)(what the medication does to the body)

Pharmacokinetics Pharmacokinetics (what the body does to the (what the body does to the

medications)medications)

– AbsorptionAbsorption

– Distribution Distribution

– EliminationElimination Half lifeHalf life LiverLiver KidneysKidneys

How to use polytherapy How to use polytherapy rationallyrationally Side effectsSide effects

– Dose-related Dose-related

– Idiosyncratic (each Idiosyncratic (each person is different)person is different)

Older MedicationsOlder Medications

Carbamazepine Carbamazepine (Tegretol)(Tegretol)

PhenobarbitalPhenobarbital

Ethosuximide (Zarontin)Ethosuximide (Zarontin)

Phenytoin Phenytoin (Dilantin/Cerebyx)(Dilantin/Cerebyx)

Valproic acid (Depakote)Valproic acid (Depakote)

Primidone (Mysoline)Primidone (Mysoline)

Newer AED’sNewer 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)

Medication choices based on Medication choices based on epilepsy type…epilepsy type…

AED’s for Partial EpilepsyAED’s for Partial Epilepsy

All but Zarontin and BanzelAll but Zarontin and Banzel

Best AED’s for Generalized Best AED’s for Generalized EpilepsyEpilepsy DepakoteDepakote KeppraKeppra LamictalLamictal Topamax Topamax ZonegranZonegran BanzelBanzel

Future MedicationsFuture Medications

– BrivaracetamBrivaracetam

– CarisbamateCarisbamate

– EslicarbazepineEslicarbazepine

– GanaxaloneGanaxalone

– LosigamoneLosigamone

– Nitrfazepam Nitrfazepam

– PerampanelPerampanel

– PiracetamPiracetam

– ProgabideProgabide

– RemacemideRemacemide

– RetigabineRetigabine

– SeletracetamSeletracetam

– StiripentolStiripentol

What Are Some What Are Some Promising New Medical Promising New Medical Treatments?Treatments? Maintenance Maintenance

TreatmentTreatment

– Ezogabine Ezogabine (Potiga)(Potiga)

– PerampanelPerampanel

– VertexVertex

Emergency Emergency TreatmentTreatment

– Intranasal Intranasal MidazolamMidazolam

PotigaPotiga

Potassium Potassium Channel OpenerChannel Opener

Partial SeizuresPartial Seizures

Rare but serious Rare but serious side effectsside effects

PeramapanelPeramapanel

Glutamate BlockerGlutamate Blocker

Effective in trials Effective in trials for partial seizuresfor partial seizures

Side effects: Side effects: Dizziness, Dizziness, SleepinessSleepiness

Approved in Approved in EuropeEurope

Under study in US Under study in US for Generalized for Generalized Seizure typesSeizure types

Under FDA review Under FDA review for Partial Seizuresfor Partial Seizures

Vx-765 for Partial Vx-765 for Partial EpilepsyEpilepsy New approach to New approach to

Epilepsy RxEpilepsy Rx

– Anti-InflammatoryAnti-Inflammatory

– Short Duration of Short Duration of therapy (weeks therapy (weeks instead of years)instead of years)

– Oral MedicineOral Medicine

Early Clinical Trials Early Clinical Trials CompletedCompleted

– Early results Early results encouraging but encouraging but longer treatment longer treatment duration to be duration to be studiedstudied

– Headache, dizziness, Headache, dizziness, GI most common side GI most common side effectseffects

Emergency TreatmentEmergency Treatment

Rectal DiastatRectal Diastat

– Clinically provenClinically proven

– Hard to giveHard to give

– Adults don’t likeAdults don’t like

– Can’t self Can’t self administeradminister

Intranasal MidazolamIntranasal Midazolam

Easy to giveEasy to give

Preferred routePreferred route

Can be self-Can be self-administered or administered or given by caretakergiven by caretaker

Under studyUnder study

Advances in TreatmentAdvances in Treatment

NewermedicationsNewermedications– BrivaracetamBrivaracetam

– CarisbamateCarisbamate

– ClobazamClobazam

– EslicarbazepineEslicarbazepine

– GanaxaloneGanaxalone

– LosigamoneLosigamone

– Nitrfazepam Nitrfazepam

– PerampanelPerampanel

– PiracetamPiracetam

– ProgabideProgabide

– RemacemideRemacemide

– RetigabineRetigabine

– SeletracetamSeletracetam

– StiripentolStiripentol

For patients that do not For patients that do not respond to medicationrespond to medication Ketogenic dietKetogenic diet SurgeriesSurgeries

Ketogenic Diet (@1920)Ketogenic Diet (@1920)

High fat, low carbohydrate/protein dietHigh fat, low carbohydrate/protein diet Requires hospitalization to start itRequires hospitalization to start it

– NPO until patient in ketosisNPO until patient in ketosis– Parent educationParent education– Meds to be taken into accountMeds to be taken into account

Recommended mainly for young children Recommended mainly for young children due to compliance and efficacy due to compliance and efficacy

Epilepsy SurgeryEpilepsy Surgery

The goals are:The goals are:

– To determine where the seizures are coming To determine where the seizures are coming fromfrom

– To make sure is safeTo make sure is safe

Epilepsy SurgeryEpilepsy Surgery

To determine where the seizures are To determine where the seizures are coming fromcoming fromVideo-EEG monitoringVideo-EEG monitoring

MRIMRI

MRSMRS: :

PETPET: :

SPECTSPECT::

MEG: MEG:

Epilepsy SurgeryEpilepsy Surgery

To make sure that it is safeTo make sure that it is safeWada testWada test: to study speech and memory: to study speech and memory

Neuropsychological testingNeuropsychological testing: mental functions : mental functions (IQ, memory, attention) and personality (IQ, memory, attention) and personality assessment assessment

Psychological evaluationPsychological evaluation

Ophthalmologic evaluationOphthalmologic evaluation

Epilepsy SurgeryEpilepsy Surgery

Some cases in which the localization is not Some cases in which the localization is not clear or where function could be affected clear or where function could be affected will require INVASIVE ELECTRODESwill require INVASIVE ELECTRODES

– Depth electrodesDepth electrodes– Subdural electrodesSubdural electrodes

Types of Epilepsy SurgeryTypes of Epilepsy Surgery

Temporal LobectomyTemporal Lobectomy Extratemporal Extratemporal

ResectionsResections HemispherectomyHemispherectomy Corpus CallosotomyCorpus Callosotomy

Outcome after epilepsy Outcome after epilepsy surgerysurgery Anterior temporal lobectomyAnterior temporal lobectomy

– 70-80% seizure free70-80% seizure free Neocortical resectionNeocortical resection

– With lesion: 50-80% seizure freeWith lesion: 50-80% seizure free– Without lesion: 30-50% seizure freeWithout lesion: 30-50% seizure free

HemispherectomyHemispherectomy– Significant improvementSignificant improvement

Corpus CallosotomyCorpus Callosotomy– Significant improvement for drop attacksSignificant improvement for drop attacks

Complications of surgeryComplications of surgery

Low rate of Low rate of complicationscomplications– InfectionsInfections

– BleedingBleeding

– AnesthesiaAnesthesia

– Function Function

Vagus Nerve Stimulator Vagus Nerve Stimulator (1997)(1997) Intractable epilepsy patient without focus or Intractable epilepsy patient without focus or

desires interim step before epilepsy surgerydesires interim step before epilepsy surgery Goal is to reduce amount/severity of seizures vs. Goal is to reduce amount/severity of seizures vs.

curecure Device surgically implanted in left chest/axilla Device surgically implanted in left chest/axilla

areaarea Coils around left vagus nerveCoils around left vagus nerve Stimulation is automatic; patient can additionally Stimulation is automatic; patient can additionally

stimulate device if aura stimulate device if aura