Transcript CME Guides - Epilepsy Group

Hackensack University Medical Center
Comprehensive Epilepsy Center
Georges A. Ghacibeh, MD, MS
Seizures vs. Epilepsy
Seizures
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)
Epilepsy
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%
Definition: Seizure vs. Epilepsy
Sz
Sz
Diagnosis
Seizure-free
No Sz
Epilepsy
Treatment
No Epilepsy
Stop Treatment
Classification of Seizures
Focal - Onset
 Simple partial
 Complex partial
 Secondarily
generalized
Generalized - Onset
 Absence
 Myoclonic
 Generalized tonic-clonic
 Tonic
 Clonic
 Atonic
Seizure Types
Generalized
Focal
Focus
Classification of Epilepsy
Seizure Onset
Etiology
Primary

Generalized


Focal


Juvenile Myoclonic
Childhood Absence
Primary GTC
Benign Rolandic
Benigh Occipital
Secondary
Lennox-Gastaut
 Other developmental
disorders


Focal-Onset Epilepsy
Epidemiology of Epilepsy
Incidence per 100,000
Epilepsy: Incidence Rates by Seizure Type*
90
80
70
60
50
40
30
20
10
0
Partial
Generalized tonic-clonic
Primary Generalized
0
10
20
30
40
50
60
70
80
Age
*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 Factor
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
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


Prenatal and Birth Injury
Febrile Convulsions
Developmental Delay
Head Trauma
CNS Infections
Brain Tumors
Brain Surgery
Family History
Evaluation and Diagnosis
 History from patient and family
 EEG: standard 20-30 minutes
 EEG Monitoring:
 Ambulatory EEG
 Video EEG
 Neuroimaging
The Tracing
Video-EEG Monitoring
 Continuous 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 Events
 Epileptic
 Focal (Partial) onset
 Generalized onset
 Non-Epileptic:
 Psychogenic
 Cardiac
 Vasovagal
 Sleep disorder
 Migraine…
Partial (focal) Seizures
 Simple 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 Seizures
 Absence: Brief staring (<30sec )
 Myoclonic: Brief, shock-like muscle contractions
 Atonic: Loss of muscle tone
 Tonic: Sustained muscle contraction
 Tonic-Clonic
Non-Epileptic Events
 Psychogenic
 Cardiovascular
 Syncope
 Metabolic (glucose, Na, Ca, Mg)
 Sleep disorders (parasomnias, cataplexy)
New Onset Seizure
 After 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 AEDs
 Patients 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 Epilepsy




Medications
Diet Therapy
Hormonal Therapy
Surgical:



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
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















Phenobarbital
Mysoline 
Dilantin
Tegretol
Depakote
Zorantin
Felbatol
Neurontin
Lamictal
Topamax
Gabitril
Trileptal
Zonegran
Keppra
Lyrica 
Frisium 
Klonopin 
Tranxene 
Banzel 
Vimpat 
Primidone
phenytoin
carbamazepine
valproic acid
ethosuxamide
felbamate
gabapentin
lamotrigine
topiramate
tiagabine
oxcarbazepine
zonisamide
levetiracetam
pregabaline
clobazam
clonazepam
chlorazepate
rufinamide
lacosamide
Rational Use of AEDs
 Indication / Guidelines by FDA, AES, AAN
 Seizure type/ Epilepsy syndrome
 Adverse effects (acute; chronic)
 Comorbid conditions
 Cost
 Age
 Gender
 Concomitant medications
 Social factors
 Pharmacokinetic profile
Rational Use of AEDs
Side Effects
Sleepiness
Cognitive
Behavioral
Metabolic :
Liver
Electrolytes
Hyperthermia
Weight gain
Ostioporosis
Bone Marrow
Age / Sex
Young Women
Elderly
Dilantin
Phenobarbital
Mysoline
Tegretol
Depakote
Zorantin
Felbatol
Neurontin
Lamictal
Topamax
Gabitril
Trileptal
Zonegran
Keppra
Lyrica
Frisium
Klonopin
Tranxene
Banzel
Vimpat
Co-morbid Conditions
Co-TRT
Migraine
Pain
Mood
Avoid
Kidney Stones
Psychiatric
Liver Disease
Bone Marrow
Drug Interactions
Cytochrome P-450:
Steroids
Chemotherapy
Coumadin
Many others…
FDA: Use of AEDs
Monotherapy
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
Partial
Generalized
Simple
Complex
Secondary
Generalized
TonicClonic
Tonic
Atonic Myoclonic
Rufinamide
PHT, CBZ, GBP,
OXC, TGB, LCS
PGB
Infantile
Spasms
ACTH
TPM
TGB
VGB
VPA, LTG, TPM, ZNS, LVT, FBM
Absence
ESX
AED Therapy
Epilepsy
Time
First AED
Increase
Dosage
Switch
AED
Combine
AEDs
Polytherapy
Trial and Error Method
Trial and Error Method
TRIAL
Adjust Dosage
ERROR
Recurrent
Seizures
Change AED
Combine AEDs
Side Effects
Rational Use of AEDs
PharMetrics. April 2002 to June 2003
IMS NPA, Dec 2003.
Kwan P, Brodie MJ. N Engl J Med
2000; 342: 314-9.
Success With Antiepileptic Drugs
Previously Untreated Epilepsy Patients (N=470)
Kwan P, Brodie MJ. N Engl J Med.
2000;342(5):314-319
Common Side Effects
 Dizziness
 Sleepiness
 Drowsiness
 Ataxia
 Blurred vision
Diet Therapy
Diet Treatment
For Epilepsy
Ketogenic Diet
Modified Atkins
Low Glycemic
Index Treatment
Energy Source: Regular Diet
Carbohydrates
Fat
Glucose
Brain
Fatty Acids
Body
Energy Source: Ketogenic Diet
Carbohydrates
Fat
Ketones
Fatty Acids
Brain
Body
Ketogenic Diet
 Very High Fat, Low Carbohydate And Protein Diet
 Fat Used As Alternative Energy Source
 Goal = Ketosis

Why?

Elevated Ketones Correlate With Optimal Seizure Control
 Fluid And Calorie Restricted
 Based On Ratio – 3:1 or 4:1
 Food Must Be Weighed
Ketogenic Diet
 Admission to the hospital 3-5 days
 Precise amounts of carbohydrates, proteins and fat
 All 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 Diet
 Easier than the ketogenic diet
 Many 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 Diet
 No Hospital Admission Required
 Allowance: 40 – 60 grams CHO/day
 Only Foods With Low Glycemic Index are allowed
 Foods quantities are not weighed but are based on
portion size
 More Flexible Lifestyle
Hormone Therapies
 Some women experience increase in seizure frequency
around their menstrual period
 Catamenial seizures
 This is believed to be due to sudden changes in levels
of hormones
 There are three types of catamenial seizures
Estradiol g/mL
Progesterone ng/mL
Serum Hormone Levels
E2
P
150 30
25
100 20
15
50 10
5
0
1
3
5
7
9
11
13
15
17
19
Day of the Cycle
E2 = estradiol; P = progesterone.
21
23 25
27
Estradiol g/mL
Progesterone ng/mL
Serum Hormone Levels
E2
P
150 30
C2
C1
25
100 20
15
50 10
5
0
1
3
5
7
9
11
13
15
17
19
21
23 25
27
Day of the Cycle
C1 = catamenial 1 (seizure pattern); C2 = catamenial 2; E2 = estradiol; P = progesterone.
Herzog AG, et al. Epilepsia. 1997;38:1082-1088.
Serum Hormone Levels
E2
P
100 25
Estradiol g/mL
Progesterone ng/mL
C3
80 20
60 15
40 10
20
5
0
1
3
5
7
9
11
13
15
17
19
Day of the Cycle
C3 = catamenial 3.
Herzog AG, et al. Epilepsia. 1997;38:1082-1088.
21
23
25
27
Catamenial Epilepsy
 Katamenios = “monthly”
 The tendency for increased seizures related to the
menstrual cycle
 Affects 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 Therapy
 Supplementation 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 Medicines
 No proven benefits in epilepsy
 Some herbal medicines may increase the risk of




seizures
Some herbal medicines may interact with seizure
medications
If 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 Medicines
Some Herbal Substances
Used In
 Borage

Anxiety
 Caffeine

Depression

Low Energy

Arthritis

Memory difficulties
 Chamomile
 Ephedra
 Evening Primrose
 Ginkgo
 Ginseng
 Herbal Essential Oils
 Kava
 Passionflower
 St. John's Wort
 Valerian
Caution
 Some may cause seizures
 Some may have bad interactions
with seizure medications or other
medications
Supplements
 Vitamins: A - E
 Minerals: Magnesium, Selenium, Zinc…
 Other: CoQ10, Carnitine, anti-oxidants, …
Supplements: The Rule
 Most supplements are probably safe if taken at the
recommended dose
 No proven efficacy in treating seizures
 BUT: Some supplements are recommended in certain
metabolic disorders affecting the function of the
mitochondria
Mitochondria
Mitochondria are small organelles inside the cells, including the brain cells.
Their function is to generate energy for the cell
Mitochondria and Seizures
 Certain mitochondrial diseases can cause seizures
 It 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
Supplements
 In 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 childbearing age
 Vitamin D and Calcium are recommended for all
patients taking seizure medications
Cognition
Sleep
Seizures
Behavior
Seizures in sleep disorders
 In 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 epilepsy
 Many patients with epilepsy have disrupted sleep
 This is usually caused by:
 Nighttime seizures
 Nighttime seizure activity
 Side effects of seizure medications
 Depression and anxiety
Sleep in patients with epilepsy
 The 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
Attention
 The relationship between sleep and seizures is very
complex
 Memory, attention difficulties and sleepiness can be due
either to:
 Seizure medications
 Lack of proper sleep
 Nighttime seizures and seizure activity
 Specific sleep disorder
 The correct diagnosis is essential!
Nighttime seizure activity
 In some patients, the EEG reveals very frequent spikes
(seizure activity) during sleep, with minimal seizure
activity while awake
 NOTE: Routine 20 minute EEG usually do not reveal
this activity
 Overnight EEG is necessary to capture and quantify
this activity
Significance
 Recent evidence suggests that patients, especially
children, with frequent nighttime spikes may develop:
 Cognitive problems
 Learning difficulties
 Behavioral problems
Autism and Seizures
 About 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 Autism
 Seizures in Autistic patients should be treated like any
other seizures
 Some patients with Autism who have frequent spikes
(seizure activity) during sleep
 It is believed that seizure activity can interfere with
learning ability, sleep and behavior
 In some cases, treating the seizure activity can help
improve learning ability and behavior
 Treatment options include medications and diet
Conclusion
 Epilepsy is a very complex medical condition
 Many effective treatment options are available
 Most patients with epilepsy achieve seizure freedom
and can live a normal and productive life
 Seizure medications are the main treatment modality
 Diet therapy should be considered in some cases
 Patients who don’t respond well to medications, may
consider epilepsy surgery