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• 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• 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 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

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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

ORTwo 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.1.800.779.0777www.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• 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

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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

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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.

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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

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Medication Selection• 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• Age• Gender• Illness• Drug interactions

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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

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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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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

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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

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

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