management of difficult to treat epilepsy in children
DESCRIPTION
Management of Difficult to Treat Epilepsy in Children. Northeast Regional Epilepsy Group. Advances in the Diagnosis and Treatment of Epilepsy. Marcelo E. Lancman, M.D. Director, Epilepsy Program Northeast Regional Epilepsy Group. Advances in the Diagnosis and Treatment of Epilepsy. - PowerPoint PPT PresentationTRANSCRIPT
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Management of Difficult to Management of Difficult to Treat Epilepsy in ChildrenTreat Epilepsy in Children
Northeast Regional Epilepsy GroupNortheast Regional Epilepsy Group
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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
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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
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Epilepsy ConceptsEpilepsy Concepts
What is epilepsy?What is epilepsy?
What is a seizure?What is a seizure?
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IncidenceIncidence
EpilepsyEpilepsy
0.5-1% 0.5-1%
SeizuresSeizures
5-10%5-10%
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Classification of SeizuresClassification of Seizures
PartialPartialSimpleSimpleComplexComplexSecondary GeneralizedSecondary Generalized
GeneralizedGeneralizedAbsenceAbsenceAtonicAtonicClonicClonicTonicTonicTonic-clonicTonic-clonicMyoclonicMyoclonic
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Classification of EpilepsyClassification of Epilepsy
By LocalizationBy Localization– PartialPartial– GeneralizedGeneralized
By CauseBy Cause– Idiopathic (unknown)Idiopathic (unknown)– SymptomaticSymptomatic
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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
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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
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Idiopathic Partial EpilepsyIdiopathic Partial Epilepsy
Benign Rolandic EpilepsyBenign Rolandic Epilepsy Benign Occipital EpilepsyBenign Occipital Epilepsy
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Symptomatic Generalized Symptomatic Generalized EpilepsyEpilepsy Infantile spasms (West syndrome)Infantile spasms (West syndrome) Dravet syndromeDravet syndrome Lennox-Gastaut syndromeLennox-Gastaut syndrome
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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 (Tuberous Sclerosis Complex, (Tuberous Sclerosis Complex,
Neurofibromatosis)Neurofibromatosis)
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Special types of EpilepsySpecial types of Epilepsy
Neonatal seizuresNeonatal seizures Landau-Kleffner syndromeLandau-Kleffner syndrome ESES (electrical status epilepticus ESES (electrical status epilepticus
during sleep)during sleep) Reflex EpilepsyReflex Epilepsy
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Type of EpilepsyType of Epilepsy
The importance of knowingThe importance of knowing
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Diagnosis of EpilepsyDiagnosis of Epilepsy
Medical HistoryMedical History Physical examPhysical exam
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TestingTesting
Testing Testing – EEG, AEEG, VEEGEEG, AEEG, VEEG– LabsLabs– GeneticsGenetics
ImagingImaging– CT, MRI (high CT, MRI (high
definition)definition)
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Diagnosis Diagnosis
Diagnosis is clear: treatment is initiatedDiagnosis is clear: treatment is initiated
Diagnosis unclear: Video-EEGDiagnosis unclear: Video-EEG
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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
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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
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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
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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
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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,
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Diagnostic AdvancesDiagnostic Advances
MagnetoencefalographyMagnetoencefalography
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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)
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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
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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
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Seizure ControlSeizure Control
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Options for the Intractable Options for the Intractable Seizure PatientSeizure Patient
Medications (combinations)Medications (combinations) DietsDiets Surgical proceduresSurgical procedures
– StimulatorsStimulators– ResectionsResections
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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
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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
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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)
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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)
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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)
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Medication choices based on Medication choices based on epilepsy type…epilepsy type…
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AED’s for Partial EpilepsyAED’s for Partial Epilepsy
All but Zarontin and BanzelAll but Zarontin and Banzel
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Best AED’s for Generalized Best AED’s for Generalized EpilepsyEpilepsy DepakoteDepakote KeppraKeppra LamictalLamictal Topamax Topamax ZonegranZonegran BanzelBanzel
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Future MedicationsFuture Medications
– BrivaracetamBrivaracetam– CarisbamateCarisbamate– EslicarbazepineEslicarbazepine– GanaxaloneGanaxalone– LosigamoneLosigamone– Nitrfazepam Nitrfazepam – PerampanelPerampanel– PiracetamPiracetam– ProgabideProgabide– RemacemideRemacemide– RetigabineRetigabine– SeletracetamSeletracetam– StiripentolStiripentol
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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
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PotigaPotiga Potassium Potassium
Channel OpenerChannel Opener
Partial SeizuresPartial Seizures
Rare but serious Rare but serious side effectsside effects
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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
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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 studiedduration to be studied
– Headache, dizziness, Headache, dizziness, GI most common side GI most common side effectseffects
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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
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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
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For patients that do not For patients that do not respond to medicationrespond to medication Ketogenic dietKetogenic diet SurgeriesSurgeries
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Epilepsy SurgeryEpilepsy Surgery
http://www.rch.unimelb.edu.au/cep/Media/brain/mri6.jpg http://www.fleni.org.ar/files/servicio_193_8
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Rates of Surgical Rates of Surgical Success*Success*
Temporal Lobectomy 70-80%Temporal Lobectomy 70-80%
““Lesion” Resection 70-80%Lesion” Resection 70-80%
““Non-Lesional” Resection 30-50%Non-Lesional” Resection 30-50%
Medical Management 5%Medical Management 5%
* Absence of Disabling Seizures
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VisualaseVisualase
•Laser Treatment
•Evaluation is same asfor epilepsy surgery
No need for open brainoperation
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VisualaseVisualase
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Neuromodulatory Neuromodulatory TreatmentsTreatments Device implanted to alter instead of Device implanted to alter instead of
destroy brain tissuedestroy brain tissue
Range of treatment possible: Range of treatment possible: Electrical, Cooling, local medicationsElectrical, Cooling, local medications– Limit body/brain side effectsLimit body/brain side effects
Improve brain function?Improve brain function?
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NeuroPaceNeuroPace
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Deep Brain Stimulation (DBS)Deep Brain Stimulation (DBS)
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What will Epilepsy Care What will Epilepsy Care Look Like in Future?Look Like in Future? Personalized Medical Personalized Medical
Choices based on Choices based on geneticsgenetics
Truly Truly Anti-epilepticAnti-epileptic therapytherapy
Treatment directed Treatment directed right at the seizure right at the seizure focusfocus