Transcript Slide 1

The Brain and Epilepsy
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Introductions- who we are?
• Amanda Pike- Education Senior Program
Manager, Epilepsy Foundation of MN
• Jeannine Conway- Pharm. D, University of
MN, member of Professional Advisory Board
of Epilepsy Foundation of MN
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Today’s Objectives
• Learn the various seizure types and describe how to
respond appropriately
• Discuss the correlation between brain injury and
epilepsy and stroke and epilepsy
• Discuss treatment options for epilepsy
• Learn about anticonvulsant medications and brain
injury
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About you?
• Where do you work?
• Have you seen a seizure?
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What is a seizure?
• Sudden electrical activity in the brain
• Seizures are either partial or generalized
• Where the activity occurs in the brain will
determine how the seizure will look
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What is epilepsy?
• A neurological disorder of the brain
characterized by the tendency to have
recurring seizures
• May also be called a Seizure Disorder
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Epilepsy facts
• Approximately 2.2 million Americans have epilepsy
• Epilepsy is the most common neurological condition in
children and the fourth most common in adults after
Alzheimer’s, stroke and migraines
• Approximately 1 in 26 people will develop epilepsy at
some point in their lives
• Over 60,000 people in MN & ND have epilepsy
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Epilepsy and stroke
• Number one cause of epilepsy in people older
than 50
• Side effects of medicine can make the effects
of the stroke a little worse
• Make sure you know about any other
medications and if it is safe to mix with any
epilepsy medications
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Epilepsy and brain injury
• Increased risk of developing epilepsy following
a traumatic brain injury
• May be treated with phenytoin to prevent
seizures up to 1 month after
• Veterans- Post traumatic epilepsy
– PTE 52% among TBI patients who have served
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Possible causes of epilepsy
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Head trauma
Brain tumor and stroke
Infection and maternal injury
Some forms are genetic
In 70% of cases there is no known cause
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Possible seizure triggers
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Assess the environment
Failure to take medications
Lack of sleep
Stress / Anxiety
Dehydration
Photosensitivity – strobe lights
Menstrual cycle / hormonal changes
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Seizure Classification
Partial Seizures (focal)
• Involves only part of brain
• Simple & complex forms
• Symptoms relate to the part of brain effected
Generalized Seizures
• Involves whole brain
• Convulsions, staring, muscle spasms, and falls
• Most common are absence & tonic-clonic
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Focal seizures w/o change in awareness
(Simple partial seizures)
 Uncontrollable shaking movements of hand, arm
or legs
 Sensory Seizures – may see flashing lights in
peripheral vision, hear bells ringing, etc.
 Seizure usually lasts between 1 and 2 minutes –
no impairment of consciousness
 May be considered an aura
 No immediate action is needed other than
reassurance and emotional support
 A medical evaluation is recommended
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Focal seizures w/o change in awareness
(Simple partial seizures)
 Uncontrollable shaking movements of hand, arm
or legs
 Sensory Seizures – may see flashing lights in
peripheral vision, hear bells ringing, etc.
 Seizure usually lasts between 1 and 2 minutes –
no impairment of consciousness
 May be considered an aura
 No immediate action is needed other than
reassurance and emotional support
 A medical evaluation is recommended
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Focal seizures with change in awareness
(Complex partial seizures)
 Most common seizure type
 Unaware of surroundings and unable to respond
 Repetitive, purposeless movements such as lip
smacking, hand wringing, or wandering - actions
seem unusual
 Seizure usually lasts approximately three minutes
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Appropriate Response
(Complex partial seizure)
 Stay calm
 Track time
 Do not restrain
 Gently direct away from hazards
 Remain with the individual until they have gained
full awareness
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Absence Seizures
(formerly petit mal)
 Usual onset between 4 and 12 years of age
 Characterized by brief staring – can be
confused with “daydreaming”
 Starts and ends abruptly - can happen several
times a day
 Quickly returns to complete awareness
 Appropriate response includes documentation
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Generalized Tonic Clonic
(formally grand mal)
 NOT the most common type
 Completely unconscious – loss of control
 Characterized by a sudden fall
 May cry out or make some types of noise
 Onset of uncontrolled jerking or shaking of muscles
 May have irregular breathing
 Lasts 5 minutes or less
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Appropriate Response
(Generalized Tonic Clonic)
 Stay calm
 Protect their head
 Turn on side to prevent choking *
 Track time
 Check for Seizure Disorder ID
 Move objects out of the way
* Do NOT put anything in the person’s mouth.
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Appropriate Response
(Generalized Tonic Clonic)
 Remain with them until they have gained full
awareness
 If seizure lasts more than 5 minutes, call EMS
 Recovery period– post ictal state
 Not included in timing of the seizure
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Call 911 if the person…
 Is injured
 Has diabetes or is pregnant
 Does not resume normal breathing or
breathing stops
 Has a 1st time seizure
 Has a seizure in water
 Situation escalates
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Also call 911 if:
STATUS EPILEPTICUS
There is more than 5 minutes
of continuous seizure activity
OR
Two or more consecutive seizures
(cluster) without complete recovery
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Treatment Options
 Medication
 Brain surgery
 Medical Devices
 Diet
 Social and psychological support
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The Epilepsy Foundation of Minnesota leads the fight to
stop seizures, find a cure and overcome the challenges
created by epilepsy.
1.800.779.0777
www.efmn.org
Connect with us:
Facebook Epilepsy-Foundation Minnesota
Twitter @EpilepsyMN
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Anticonvulsants and Brain
Injury
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Objectives
• Describe the elements of epilepsy treatment
including:
– Available treatments
– Desired outcomes
– Describe medication choices
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Indications for AEDs
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Epilepsy
Headache
Psychiatric disorders
Neuropathic pain
Behavior
Weight loss
Movement disorders
Spasticity
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Goals of epilepsy care
• Eliminate seizures with no side effects;
alternatively
– Reduce the number
– Decrease the severity
– Minimize side effects
• Optimize quality of life
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Chronology of AED Development
2nd generation AEDs
Year
Drug
1993
1994
1994
1996
1997
1999
1999
2000
2005
2009
2009
2011
Year
2009
2011
2012
Felbamate
Gabapentin
Lamotrigine
Topiramate
Tiagabine
Oxcarbazepine
Levetiracetam
Zonisamide
Pregabalin
Rufinamide
Vigabatrin
Clobazam
3rd generation AEDs
Drug
Lacosamide
Ezogabine
Perampanel
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Normal CNS Function
Excitation
Glutamate
Aspartate
Inhibition
GABA
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Abnormal Excitation
Glutamate
Aspartate
Excitation
Inhibition
GABA
Furthermore, membrane depolarization leads
to enhanced excitatory receptor function and
reduced GABA-receptor function. This pattern
of ‘voltage-dependence’ leads to an even
greater level of excitation.
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AEDs Act By Restoring Balance
Inhibition
Excitation
Reduce excitation
Phenytoin (PHT)
Carbamazepine (CBZ)
Valproic acid (VPA)
Felbamate (FBM)
Lamotrigine (LTG)
Topiramate (TPM)
Oxcarbazepine (OXC)
Zonisamide (ZNS)
Levetiracetam (LEV)
Increase inhibition
Phenobarbital (PB)
Benzodiazepines (BDZ)
VPA
FBM
TPM
ZNS
Tiagabine
Vigabatrin
New onset seizures
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Medication Selection
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Seizure type
Co-medications
Medical conditions
Age of the patient
Insurance coverage
Allergies
Adherence challenges
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Optimize Therapy
• Titrate dose or serum concentration to
response
• Increase dose until seizure control is attained
or until unacceptable side effects occur
• Consider adding 2nd AED if first is not
effective
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Monitoring AED Treatment
• Efficacy
– Seizure control
• Toxicity
– Side effects
– Serum concentrations
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Toxicity
• Acute side effects
– Concentration dependent
• Common, bothersome, generally not life threatening
• Reversible by decreasing the serum concentration
• Examples: dizziness, ataxia, headache
– Idiosyncratic
• Rare, may be serious and life threatening
• Generally involve organ hypersensitivity
• Examples: hepatic failure, rash, aplastic anemia
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Toxicity
• Chronic Side Effects
– Due to long term exposure to the medication
– Occur regardless of serum concentration levels
– Examples: Alopecia, weight gain, behavior change,
cognitive impairment
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Challenges in Using AEDs
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Age
Gender
Illness
Drug interactions
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Types of Drug Interactions
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Drug-drug: Valproic acid and lamotrigine
Drug-food: Carbamazepine and grapefruit juice
Drug-dietary supplement: Calcium and phenytoin
Drug-herbal: indinavir and St. John’s Wort
Drug-disease: medications that lower the seizure
threshold and epilepsy
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Removing Medication from Body
• Elimination is two processes:
– Metabolism: a chemical reaction that changes the drug so
the body can get rid of it
– Excretion: removing the drug from the body
• Blood moves drug to liver and kidney to be “disposed of”
• Even if drug moves into non-eliminating tissues (like brain), it
must get back to blood and moved to the liver and kidney’s
for disposal
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Metabolism
Changes one chemical (drug)
into another for removal from
the body via enzymes
Enzymes are proteins that
help chemical reactions
along
If you know how a drug is
metabolized
=Help predict interactions
http://www.cincinnatichildrens.org/svc/alpha/l/liver/liver-anatomy.htm
Major Liver Enzymes
P450 Enzyme
Examples of Drug That Use The Enzyme
CYP1A2
Caffeine, Theophylline
CYP2B6
CYP2C9
Bupropion
Warfarin, Phenytoin, Phenobarbital, NSAIDs
CYP2C19
Omeprazole, Phenytoin, S-Mephenytoin
CYP2D6
Metoprolol, Fluoxetine
Codeine, Dextromethorphan
Carbamazepine, Zonisamide, Tiagabine,
Ethosuximde, Cyclosporin, Triazolam,
Amlodipine, Atorvastatin, Erythromycin
CYP3A4
http://medicine.iupui.edu/flockhart/
Excretion
Drug is removed from
the body in urine
http://www.nlm.nih.gov/medlineplus/ency/imagepages/1101.htm
Not everyone is the same
No 2D6=lack of pain relief
CYP 2D6
Codeine
(inactive)
Morphine
(active)
Approximately 7-10% of the US
population is deficient in CYP 2D6
Codeine glucuronide
(inactive)
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Summary
• Many medication options available
• Medication choice driven by several factors
– Seizure type
– Medical conditions
– Other medications
• Drug interactions can usually be proactively
managed
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AED abbreviations
1st generation AEDs
Year
Drug
PB Phenobarbital
PHT
Phenytoin
PRM
Primidone
ESM
Ethosuximide
DZP
Diazepam
CBZ
Carbamazepine
Clonazepam
VPA
Valproate
2nd generation AEDs
Year
Drug
FBM
Felbamate
GBP
Gabapentin
LTG Lamotrigine
TPM
Topiramate
TGB
Tiagabine
OXC
Oxcarbazepine
LEV Levetiracetam
ZNS Zonisamide
PGB
Pregabalin
RUF
Rufinamide
VGB
Vigabatrin
CLB
Clobazam
3rd generation AEDs
Year
Drug
LAC
Lacosamide
EZG
Ezogabine
Questions?
Jeannine Conway
Amanda Pike
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