Download New Treatments for Children and Adults With Seizures

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
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Epilepsy concepts
Diagnosing Epilepsy
What causes Epilepsy
Treating Epilepsy
New developments
Epilepsy Concepts
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What is epilepsy?
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What is a seizure?
Incidence
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Epilepsy
0.5-1%
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Seizures
5-10%
Classification of Seizures
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Partial
Simple
Complex
Secondary Generalized
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Generalized
Absence
Atonic
Clonic
Tonic
Tonic-clonic
Myoclonic
Classification of Epilepsy
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By Localization
– Partial
– Generalized
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By Cause
– Idiopathic (unknown)
– Symptomatic
Classification of Epilepsy
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Idiopathic Partial Epilepsy
Symptomatic Partial Epilepsy
Idiopathic Generalized Epilepsy
Symptomatic Generalized Epilepsy
Idiopathic Generalized
Epilepsy
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Benign Neonatal Familial Epilepsy
Benign Myoclonic Epilepsy of Infancy
Generalized epilepsy with febrile seizures plus
Epilepsy with myoclonic absence
Epilepsy with myoclonic-astatic seizures
Childhood absence epilepsy
Juvenile absence epilepsy
Epilepsy with GTCS only
Idiopathic Partial Epilepsy
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Benign Rolandic Epilepsy
Benign Occipital Epilepsy
Symptomatic Generalized
Epilepsy
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Infantile spasms (West syndrome)
Dravet syndrome
Lennox-Gastaut syndrome
Symptomatic Partial Epilepsy
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Temporal Lobe Epilepsy
Frontal Lobe Epilepsy
Parietal Lobe Epilepsy
Occipital Lobe Epilepsy
(Tuberous Sclerosis Complex,
Neurofibromatosis)
Special types of Epilepsy
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Neonatal seizures
Landau-Kleffner syndrome
ESES (electrical status epilepticus
during sleep)
Reflex Epilepsy
Type of Epilepsy
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The importance of knowing
Diagnosis of Epilepsy
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Medical History
Physical exam
Testing
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Testing
– EEG, AEEG, VEEG
– Labs
– Genetics
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Imaging
– CT, MRI (high
definition)
Diagnosis
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Diagnosis is clear: treatment is initiated
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Diagnosis unclear: Video-EEG
Video-EEG Monitoring
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Continuous EEG monitoring along with
continuous audio-video recording
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Mostly requires inpatient admission
Goals of Video-EEG
Monitoring
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Epilepsy vs. nonepileptic events
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Characterize epilepsy
type
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Pre-surgical
evaluation
Non-Epileptic Events
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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
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Physiologic (other medical conditions)
– Fainting, low sugar, changes in electrolytes,
toxins, fever.
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Psychological
– Referred to psychiatry and neuropsychologist
who work with this type of stress-seizure
– Psychiatric medication, psychotherapy,
education
Non-epileptic events
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Conditions that may look like seizures:
– TIAs, complicated migraines, movement
disorders, sleep disorders, anxiety/panic
disorder, vertigo, cardiac disorders, rage
attacks, breath-holding spells,
Diagnostic Advances
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Magnetoencefalography
What causes of Epilepsy?
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The seizure threshold
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)
Seizure Triggers
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Alcohol, stress, environmental
temperature, lights, fever/illness, hormonal
changes, hyperventilation, sleep
deprivation, medications and supplements,
missing medication doses and travel across
time zones
Treating Epilepsy
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What is intractable epilepsy?
Despite medical management, patient
continues to have frequent, debilitating
seizures
Seizure Control
Options for the Intractable
Seizure Patient
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Medications (combinations)
Diets
Surgical procedures
– Stimulators
– Resections
Medications
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Choices based on epilepsy type, patient profile, side
effect profile, cost
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Best to have patient on single antiepileptic drug (AED)
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May need polytherapy (combination of medications)
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Adding meds requires going up slowly with the new
agent before discontinuing previous drug
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Polytherapy requires deep knowledge of interactions
How to use polytherapy
rationally
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Pharmacodynamics
(what the medication does to the
body)
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Pharmacokinetics
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(what the body does to the
medications)
– Absorption
– Distribution
– Elimination
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Half life
Liver
Kidneys
How to use polytherapy
rationally
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Side effects
– Dose-related
– Idiosyncratic (each
person is different)
Older Medications
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Carbamazepine
(Tegretol)
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Phenytoin
(Dilantin/Cerebyx)
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Phenobarbital
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Valproic acid (Depakote)
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Ethosuximide (Zarontin)
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Primidone (Mysoline)
Newer AED’s
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Gabapentin (Neurontin)
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Oxcarbazepine (Trileptal)
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Lamotrigine (Lamictal)
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Pregabalin (Lyrica)
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Topiramate (Topamax)
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Zonisamide (Zonegran)
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Felbamate (Felbatol)
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Levetiracetam (Keppra)
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Diastat (Diazepam)
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Lacosamide (Vimpat)
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Vigabatrin (Sabril)
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Rufinamide (Banzel)
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Ezogabine (Potiga)
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Clobazam (Onfi)
Medication choices based on
epilepsy type…
AED’s for Partial Epilepsy
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All but Zarontin and Banzel
Best AED’s for Generalized
Epilepsy
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Depakote
Keppra
Lamictal
Topamax
Zonegran
Banzel
Future Medications
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Brivaracetam
Carisbamate
Eslicarbazepine
Ganaxalone
Losigamone
Nitrfazepam
Perampanel
Piracetam
Progabide
Remacemide
Retigabine
Seletracetam
Stiripentol
What Are Some Promising
New Medical Treatments?
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Maintenance
Treatment
– Ezogabine (Potiga)
– Perampanel
– Vertex
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Emergency
Treatment
– Intranasal
Midazolam
Potiga
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Potassium Channel
Opener
Partial Seizures
Rare but serious
side effects
Peramapanel
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Glutamate Blocker
Effective in trials for
partial seizures
Side effects:
Dizziness,
Sleepiness
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Approved in Europe
Under study in US
for Generalized
Seizure types
Under FDA review
for Partial Seizures
Vx-765 for Partial
Epilepsy
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New approach to
Epilepsy Rx
– Anti-Inflammatory
– Short Duration of
therapy (weeks
instead of years)
– Oral Medicine
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Early Clinical Trials
Completed
– Early results
encouraging but
longer treatment
duration to be studied
– Headache, dizziness,
GI most common side
effects
Emergency Treatment
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Rectal Diastat
– Clinically proven
– Hard to give
– Adults don’t like
– Can’t self administer
Intranasal Midazolam
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Easy to give
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Preferred route
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Can be selfadministered or
given by caretaker
Under study
For patients that do not
respond to medication
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Ketogenic diet
Surgeries
Epilepsy Surgery
http://www.rch.unimelb.edu.au/cep/Media/brain/mri6.jpg
http://www.fleni.org.ar/files/servicio_193_8
Rates of Surgical
Success*
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Temporal Lobectomy
70-80%
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“Lesion” Resection
70-80%
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“Non-Lesional” Resection
30-50%
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Medical Management
5%
* Absence of Disabling Seizures
Visualase
•Laser Treatment
•Evaluation is same as
for epilepsy surgery
No need for open brain
operation
Visualase
Implant
• Probe inserted in OR
• Transferred to MRI
• Laser Treatment
• MRI monitors safety of
Treatment
Laser Rx real-time
• Probe Removed
Follow up • Patient can leave same day
Neuromodulatory
Treatments
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Device implanted to alter instead of
destroy brain tissue
Range of treatment possible:
Electrical, Cooling, local medications
– Limit body/brain side effects
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Improve brain function?
NeuroPace
Implant
• Device under skull
• Leads to seizure
focus
• Detects seizure
• Electrical treatment
Treatment
delivered
• MD reviews
• Fine tunes
Follow up
treatment
Deep Brain Stimulation (DBS)
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What will Epilepsy Care
Look Like in Future?
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Personalized Medical
Choices based on
genetics
Truly Anti-epileptic
therapy
Treatment directed right
at the seizure focus