georges a. ghacibeh, md, ms hackensack university medical center comprehensive epilepsy center
TRANSCRIPT
Georges A. Ghacibeh, MD, MS
Hackensack University Medical CenterHackensack University Medical Center
Comprehensive Epilepsy CenterComprehensive Epilepsy Center
A transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain
Incidence: approximately 80/100,000 per year
Lifetime prevalence: 9% (1/3 benign febrile convulsions)
A disorder of the brain characterized by an enduring predisposition to generate epileptic seizures and by the neurobiologic, cognitive, psychological, and social consequences of this condition
Incidence: approximately
45/100,000 per year
Point prevalence: 0.5-1% (2.5 million) Cumulative risk of epilepsy: 1.3% - 3.1%
Seizures Epilepsy
Sz Sz
Epilepsy
Treatment
Diagnosis
Seizure-free
Stop Treatment
No Sz
No Epilepsy
Classification of Seizures
Focal - Focal - OnsetOnset
Simple partialComplex
partialSecondarily
generalized
Generalized - Generalized - OnsetOnset
AbsenceMyoclonicGeneralized tonic-clonicTonicClonicAtonic
GeneralizedGeneralized FocalFocal
FocusFocus
Classification of Epilepsy
Juvenile Myoclonic Childhood Absence Primary GTC
Lennox-Gastaut Other developmental disorders
Benign Rolandic Benigh Occipital
Focal-Onset Epilepsy
EtiologyEtiology
Sei
zure
On
set
Sei
zure
On
set Primary Secondary
Focal
Generalized
010
2030
4050
6070
8090
0 10 20 30 40 50 60 70 80
Age
Inci
den
ce p
er 1
00,0
00
Partial
Generalized tonic-clonic
Primary Generalized
Epilepsy: Incidence Rates by Seizure Type*Epilepsy: Incidence Rates by Seizure Type*
*Data from Rochester, Minn (1935-1979). Adapted with permission from Annegers JF.
In: The Treatment of Epilepsy: Principles and Practice. 2nd ed. Baltimore, Md: Williams & Wilkins; 1997:165-172.
Seizure Risk FactorPrenatal and Birth InjuryFebrile ConvulsionsDevelopmental DelayHead TraumaCNS InfectionsBrain TumorsBrain SurgeryFamily History
Evaluation and DiagnosisHistory from patient and family
EEG: standard 20-30 minutes
EEG Monitoring:Ambulatory EEGVideo EEG
Neuroimaging
The Tracing
Video-EEG MonitoringContinuous synchronized EEG and Video
recording
Monitors patient’s behavior and EEG
Scalp: Electrodes Similar to EEG
Invasive: Electrodes within or on the surface of the brain.
Paroxysmal EventsEpileptic
Focal (Partial) onsetGeneralized onset
Non-Epileptic: PsychogenicCardiacVasovagalSleep disorderMigraine…
Partial (focal) SeizuresSimple Partial Seizure
no loss of awareness
Complex Partial Seizure Impaired consciousness w w/o aura Clinical manifestations vary with origin & degree of
spread
Clinical Manifestations: Automatisms (manual, oral) Bicycling and fencing posture (frontal)
Duration (typically 30 seconds to 3 minutes)
Amnesia for event
Partial Seizure with Secondary Generalization
Primarily Generalized SeizuresAbsence: Brief staring (<30sec )
Myoclonic: Brief, shock-like muscle contractions
Atonic: Loss of muscle tone
Tonic: Sustained muscle contraction
Tonic-Clonic
Psychogenic
Cardiovascular
Syncope
Metabolic (glucose, Na, Ca, Mg)
Sleep disorders (parasomnias, cataplexy)
New Onset SeizureAfter the first seizure, no clear indication for
treatment
Routine EEG is usually of low yield
Long term EEG monitoring is sometimes indicated to determine need for long term treatment with AEDs.
What Type of Seizure was it?Type Recurrence Risk (2 years)
Provoked, no brain injury 3%
Provoked, brain injury 10%
Single, Unprovoked 42%
Recurrent, Unprovoked 70-80%Pohlmann-Eden, BMJ, 2006.
Discontinue AEDsPatients who are seizure-free for over 2 years
wanting to come-off AEDs
Monitoring for 48 – 72 hourse OFF anti-epileptic drugs
Seizure activity (spikes) on EEG indicate high risk of seizure recurrence.
Treatment of EpilepsyMedicationsDiet TherapyHormonal TherapySurgical:
Resective Multiple Subpial Transaction Vagus Nerve Stimulator
Experimental: Deep Brain Stimulation Radiosurgery Cortical Stimulation
Anti-Epileptic Drugs (AED)A drug that decreases the frequency and/or
severity of seizures in patients with epilepsy
Treats the symptom of seizures, not the underlying epileptic condition
Goal—maximize quality of life by minimizing seizures and adverse drug effects
Available AEDs Phenobarbital Mysoline Primidone Dilantin phenytoin Tegretol carbamazepine Depakote valproic acid Zorantin ethosuxamide Felbatol felbamate Neurontin gabapentin Lamictal lamotrigine Topamax topiramate Gabitril tiagabine Trileptal oxcarbazepine Zonegran zonisamide Keppra levetiracetam Lyrica pregabaline Frisium clobazam Klonopin clonazepam Tranxene chlorazepate Banzel rufinamide Vimpat lacosamide
Rational Use of AEDs Indication / Guidelines by FDA, AES, AANSeizure type/ Epilepsy syndromeAdverse effects (acute; chronic)Comorbid conditionsCostAgeGenderConcomitant medicationsSocial factorsPharmacokinetic profile
Side Effects Co-morbid Conditions
Drug Interactions
Age / Sex
SleepinessCognitiveBehavioralMetabolic : Liver Electrolytes Hyperthermia Weight gain OstioporosisBone Marrow
Co-TRTCo-TRT AvoidAvoid
MigrainePainMood
Kidney StonesPsychiatricLiver DiseaseBone Marrow
Cytochrome P-450:SteroidsChemotherapyCoumadinMany others…Young Women
Elderly
DilantinPhenobarbitalMysolineTegretolDepakoteZorantinFelbatolNeurontinLamictalTopamaxGabitrilTrileptalZonegranKeppraLyrica FrisiumKlonopinTranxeneBanzelVimpat
FDA: Use of AEDsMonotherapy
Carbamazepine
Valproate
Ethosuximide
Oxcarbazepine
Phenobarbital
Phenytoin
Primidone
Felbamate
Lamotrigine
Topiramate
Adjunct Therapy
Carbamazepine Lacosimide
Levetiracetam Rufinamide
Gabapentin Zonisamide
Ethosuximide Phenobarbital
Oxcarbazepine Phenytoin
Tiagabine Primidone
Topiramate Valproate
Pregabaline Lacosamide
AED Treatment Options
Tonic-Clonic
Atonic MyoclonicInfantileSpasms
AbsenceTonic
GeneralizedPartialSimple
Complex
SecondaryGeneralized
ACTHTPMTGBVGB
ESXPHT, CBZ, GBP, OXC, TGB, LCS
PGB
VPA, LTG, TPM, ZNS, LVT, FBM
Rufinamide
AED TherapyEpilepsy
First AEDIncrease Dosage
Switch AED
Combine AEDs
Polytherapy
Trial and Error MethodTrial and Error Method
Time
TRIALTRIAL ERRORERROR
Adjust Dosage
Change AED
Combine AEDs
Recurrent Seizures
Side Effects
Rational Use of AEDs
PharMetrics. April 2002 to June 2003IMS NPA, Dec 2003.Kwan P, Brodie MJ. N Engl J Med 2000; 342: 314-9.
Success With Antiepileptic Drugs
Kwan P, Brodie MJ. N Engl J Med. 2000;342(5):314-319
Previously Untreated Epilepsy Patients (N=470)
Common Side Effects
DizzinessSleepinessDrowsinessAtaxiaBlurred vision
Diet Therapy
Diet Treatment For Epilepsy
Ketogenic Diet Modified AtkinsLow Glycemic Index Treatment
Carbohydrates
Fat
Glucose
Brain Body
Fatty Acids
Carbohydrates
Fat
KetoneKetoness
Brain Body
Fatty Acids
Ketogenic DietVery High Fat, Low Carbohydate And
Protein DietFat Used As Alternative Energy SourceGoal = Ketosis
Why? Elevated Ketones Correlate With Optimal Seizure
Control
Fluid And Calorie RestrictedBased On Ratio – 3:1 or 4:1Food Must Be Weighed
Ketogenic DietAdmission to the hospital 3-5 daysPrecise amounts of carbohydrates, proteins
and fatAll food needs to be weighed
Strict monitoring of urine ketones and blood work
All medications, including over-the-counter medications, such as Motrin and Tylenol have to be keto-friendly
Modified Atkins DietEasier than the ketogenic dietMany advantages over ketogenic diet:
No admission to the hospital Only carbohydrates are measured and
restricted Start at 10 gm per day, then increase to 15-20 gm
per day No Protein Restriction No Fluid Restriction No Weighing Food
www.atkinsforseizures.com
Compare And Contrast Carbohydrate Fat Protein
Ketogenic 2% 90% 8%
Modified Atkins
6% 64% 30%
Average American
~50-55% ~25-30% ~10-15%
Low Glycemic Index DietNo Hospital Admission RequiredAllowance: 40 – 60 grams CHO/dayOnly Foods With Low Glycemic Index are
allowedFoods quantities are not weighed but are
based on portion sizeMore Flexible Lifestyle
Hormone TherapiesSome women experience increase in seizure
frequency around their menstrual periodCatamenial seizures
This is believed to be due to sudden changes in levels of hormones
There are three types of catamenial seizures
E2 = estradiol; P = progesterone.
Estradiol g/mLProgesterone ng/mL
0
5
10
15
50
20100
30150
E2 P
1 3 5 7 9 11 13 15 17 19 21 23 25 27
Day of the Cycle
Ser
um
Ho
rmo
ne
Lev
els
25
C1 = catamenial 1 (seizure pattern); C2 = catamenial 2; E2 = estradiol; P = progesterone.
Herzog AG, et al. Epilepsia. 1997;38:1082-1088.
Estradiol g/mLProgesterone ng/mL
0
5
10
15
50
20100
30150
E2 P
1 3 5 7 9 11 13 15 17 19 21 23 25 27
Day of the Cycle
C1
Ser
um
Ho
rmo
ne
Lev
els
25
C2
C3 = catamenial 3.
Herzog AG, et al. Epilepsia. 1997;38:1082-1088.
1
0
520
1040
1560
2080
25100
E2 P
3 5 7 9 11 13 15 17 19 21 23 25 27
Day of the Cycle
C3Estradiol g/mLProgesterone ng/mL
Ser
um
Ho
rmo
ne
Lev
els
Catamenial EpilepsyKatamenios = “monthly”The tendency for increased seizures
related to the menstrual cycleAffects 30%-40% of women with epilepsy
Note: Catamenial seizure patterns will be apparent only during ovulatory cycles, and 30% of cycles in women with epilepsy are anovulatory
Herzog AG, et al. Epilepsia. 1997;38:1082-1088.
Hormone TherapySupplementation of Progesterone during the
period of increased seizures is effective in reducing seizures
Oral natural progesterone is the most effective Give for 7 days starting on day 23 of the cycle
Treatment with intramuscular progesterone is sometimes effective (Depo-Provera)
Some seizure medications shorten the half-life of Depo-Provera and more frequent injections are necessary (every 10 or 8 weeks instead of every 12 weeks)
Herbal MedicinesNo proven benefits in epilepsySome herbal medicines may increase the risk of
seizuresSome herbal medicines may interact with
seizure medicationsIf you plan on trying an herbal medicine, first
research it thoroughly and consult with your doctor
NEVER substitute an herbal medicine for your regular seizure medications
http://www.mskcc.org/mskcc/html/11570.cfm
Herbal MedicinesSome Herbal Substances
Used In Borage Caffeine Chamomile Ephedra Evening Primrose Ginkgo Ginseng Herbal Essential Oils Kava Passionflower St. John's Wort Valerian
Some may cause seizures Some may have bad
interactions with seizure medications or other medications
Caution
Anxiety Depression Low Energy Arthritis Memory difficulties
SupplementsVitaminsVitamins: A - E
MineralsMinerals: Magnesium, Selenium, Zinc…
OtherOther: CoQ10, Carnitine, anti-oxidants, …
Supplements: The RuleMost supplements are probablyprobably safe if taken
at the recommended doseNo proven efficacy in treating seizuresBUTBUT: Some supplements are recommended
in certain metabolic disorders affecting the function of the mitochondria
Mitochondria are small organelles inside the cells, including the brain cells. Their function is to generate energy for the cell
Mitochondria and SeizuresCertain mitochondrial diseases can cause
seizuresIt is possible that some patients with
epilepsy might have an un-diagnosed mitochondrial disease as a cause of their seizures
It is not know if repeated seizures exhaust the energy source of the brain and lead to mitochondrial dysfunction
SupplementsIn some cases, a combination of
supplements and vitamins that support the energy production in the brain might be helpful
These are not recommended in everybody, but are safe
Some supplements include: Co-Q10, Carnitine, Vitamin B1, B5, B6, C, and E, Lipoic Acid
Folic acid is recommended in all women of child-bearing age
Vitamin D and Calcium are recommended for all patients taking seizure medications
Sleep Seizures
Cognition
Behavior
Seizures in sleep disordersIn patient with epilepsy
Evaluation for a sleep disorder should be done if the patient has the right symptoms
Treatment of the sleep disorder often leads to marked improvement in seizure control
In children, sleep disorder sometimes manifest as behavioral and learning problems. Treatment can improve both.
Sleep in patients with epilepsyMany patients with epilepsy have disrupted
sleepThis is usually caused by:
Nighttime seizuresNighttime seizure activitySide effects of seizure medicationsDepression and anxiety
Sleep in patients with epilepsyThe most common sleep symptoms in
patients with epilepsy are:
Insomnia: Trouble falling asleep Frequent night time arousals
Excessive sleepiness: Frequently due to side effects of medications Sometimes due to sleep disruption form nighttime
seizures and seizure activity
AttentionThe relationship between sleep and seizures is
very complex
Memory, attention difficulties and sleepiness can be due either to:
Seizure medicationsLack of proper sleep
Nighttime seizures and seizure activity Specific sleep disorder
The correct diagnosis is essential!
Nighttime seizure activityIn some patients, the EEG reveals very
frequent spikes (seizure activity) during sleep, with minimal seizure activity while awake
NOTENOTE: Routine 20 minute EEG usually do not reveal this activity
Overnight EEG is necessary to capture and quantify this activity
SignificanceRecent evidence suggests that patients,
especially children, with frequent nighttime spikes may develop:
Cognitive problemsLearning difficultiesBehavioral problems
Autism and SeizuresAbout 30% of patients with autism
experience seizures
About 60% of patients with autism have seizure activity on the EEG
The relationship between Autism and Seizures is complex
Seizures, EEG and AutismSeizures in Autistic patients should be
treated like any other seizures
Some patients with Autism who have frequent spikes (seizure activity) during sleepIt is believed that seizure activity can interfere
with learning ability, sleep and behaviorIn some cases, treating the seizure activity can
help improve learning ability and behaviorTreatment options include medications and diet
ConclusionEpilepsy is a very complex medical conditionMany effective treatment options are availableMost patients with epilepsy achieve seizure
freedom and can live a normal and productive lifeSeizure medications are the main treatment
modalityDiet therapy should be considered in some casesPatients who don’t respond well to medications,
may consider epilepsy surgery