New Treatments for Children and Adults With Seizures

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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




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
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
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


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)
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