The Brain and Epilepsy
efmn.org
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
efmn.org
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
efmn.org
About you?• Where do you work?• Have you seen a seizure?
efmn.org
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
efmn.org
What is epilepsy?• A neurological disorder of the brain
characterized by the tendency to have recurring seizures
• May also be called a Seizure Disorder
efmn.org
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
efmn.org
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
efmn.org
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
efmn.org
Possible causes of epilepsy• Head trauma• Brain tumor and stroke• Infection and maternal injury• Some forms are genetic• In 70% of cases there is no known cause
efmn.org
Possible seizure triggers• Assess the environment • Failure to take medications• Lack of sleep• Stress / Anxiety• Dehydration• Photosensitivity – strobe lights• Menstrual cycle / hormonal changes
efmn.org
Seizure ClassificationPartial 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
efmn.org
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
efmn.org
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
efmn.org
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
efmn.org
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
efmn.org
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
efmn.org
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
efmn.org
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.
efmn.org
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
efmn.org
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
efmn.org
Also call 911 if:STATUS EPILEPTICUS
There is more than 5 minutes of continuous seizure activity
ORTwo or more consecutive seizures
(cluster) without complete recovery
efmn.org
Treatment Options Medication
Brain surgery
Medical Devices
Diet
Social and psychological support
efmn.org
The Epilepsy Foundation of Minnesota leads the fight to stop seizures, find a cure and overcome the challenges created by
epilepsy.1.800.779.0777www.efmn.org
Connect with us: Facebook Epilepsy-Foundation Minnesota
Twitter @EpilepsyMN
efmn.org
Anticonvulsants and Brain Injury
efmn.org
Objectives• Describe the elements of epilepsy treatment
including:– Available treatments– Desired outcomes– Describe medication choices
efmn.org
Indications for AEDs• Epilepsy• Headache• Psychiatric disorders• Neuropathic pain • Behavior• Weight loss• Movement disorders• Spasticity
efmn.org
Goals of epilepsy care• Eliminate seizures with no side effects;
alternatively– Reduce the number – Decrease the severity– Minimize side effects
• Optimize quality of life
efmn.org
Chronology of AED Development
efmn.org
2nd generation AEDsYear Drug1993 Felbamate1994 Gabapentin1994 Lamotrigine1996 Topiramate1997 Tiagabine1999 Oxcarbazepine1999 Levetiracetam2000 Zonisamide2005 Pregabalin2009 Rufinamide2009 Vigabatrin2011 Clobazam
3rd generation AEDsYear Drug2009 Lacosamide2011 Ezogabine2012 Perampanel
Normal CNS Function
efmn.org
ExcitationInhibition
GlutamateAspartate
GABA
Abnormal Excitation
Excitation
Inhibition
GABA
GlutamateAspartate
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.
efmn.org
AEDs Act By Restoring Balance
Reduce excitationPhenytoin (PHT)
Carbamazepine (CBZ)Valproic acid (VPA)Felbamate (FBM)Lamotrigine (LTG)Topiramate (TPM)
Oxcarbazepine (OXC)Zonisamide (ZNS)
Levetiracetam (LEV)
Increase inhibitionPhenobarbital (PB)
Benzodiazepines (BDZ)VPAFBMTPMZNS
TiagabineVigabatrin
ExcitationInhibition
New onset seizures
efmn.org
Medication Selection• Seizure type• Co-medications• Medical conditions• Age of the patient• Insurance coverage• Allergies• Adherence challenges
efmn.org
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
efmn.org
Monitoring AED Treatment• Efficacy– Seizure control
• Toxicity– Side effects– Serum concentrations
efmn.org
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
efmn.org
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
efmn.org
Challenges in Using AEDs• Age• Gender• Illness• Drug interactions
efmn.org
Types of Drug Interactions• 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
efmn.org
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
efmn.org
http://www.cincinnatichildrens.org/svc/alpha/l/liver/liver-anatomy.htm
MetabolismChanges one chemical (drug) into another for removal from the body via enzymes
If you know how a drug is metabolized
=Help predict interactions
Enzymes are proteins that help chemical reactions along
Major Liver Enzymes P450 Enzyme Examples of Drug That Use The Enzyme
CYP1A2 Caffeine, Theophylline
CYP2B6 Bupropion
CYP2C9 Warfarin, Phenytoin, Phenobarbital, NSAIDs
CYP2C19 Omeprazole, Phenytoin, S-Mephenytoin
CYP2D6 Metoprolol, FluoxetineCodeine, Dextromethorphan
CYP3A4 Carbamazepine, Zonisamide, Tiagabine, Ethosuximde, Cyclosporin, Triazolam, Amlodipine, Atorvastatin, Erythromycin
http://medicine.iupui.edu/flockhart/
Excretion
http://www.nlm.nih.gov/medlineplus/ency/imagepages/1101.htm
Drug is removed from the body in urine
Not everyone is the sameNo 2D6=lack of pain relief
Codeine(inactive)
Morphine(active)
CYP 2D6
Codeine glucuronide(inactive)
Approximately 7-10% of the US population is deficient in CYP 2D6
efmn.org
Summary• Many medication options available• Medication choice driven by several factors– Seizure type– Medical conditions– Other medications
• Drug interactions can usually be proactively managed
efmn.org
AED abbreviations
2nd generation AEDsYear DrugFBM FelbamateGBP GabapentinLTG LamotrigineTPM TopiramateTGB TiagabineOXC OxcarbazepineLEV LevetiracetamZNS ZonisamidePGB PregabalinRUF RufinamideVGB VigabatrinCLB Clobazam
1st generation AEDsYear DrugPB PhenobarbitalPHT PhenytoinPRM PrimidoneESM
EthosuximideDZP DiazepamCBZ Carbamazepine
ClonazepamVPA Valproate3rd generation AEDs
Year DrugLAC LacosamideEZG Ezogabine
Questions?
Jeannine ConwayAmanda Pike
efmn.org