Brain Injury and Seizures

www.efmn.org | 1600 University Avenue West, Suite 300, St. Paul, MN 55104 |

A little bit about your presenters

• • Amanda Pike- Epilepsy Foundation of MN Jeannine Conway- University of MN, EFMN PAB 2

Today’s Objectives

 Define epilepsy and discuss the correlation between brain injuries and strokes with seizures  Identify the most common types of seizures and describe appropriate response  Discuss available treatment options 3

Epilepsy is…

 A neurological disorder of the brain characterized by the tendency to have recurring seizures  May also be called a Seizure Disorder 4

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 5

Epilepsy and stroke

• Number 1 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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What happens to the brain during a seizure?

 Sudden electrical activity in the brain  Most seizures are either partial or generalized  Where the activity occurs in the brain will determine how the seizure will look 7

Possible Causes of Epilepsy

 Head Trauma  Brain tumor and stroke  Infection and maternal injury  Some forms are genetic 8

In 70% of the epilepsy 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 10

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 11

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 12

Complex Partial Seizures

 Most common seizure type   Repetitive, purposeless movements such as lip smacking, hand wringing, or wandering - actions seem unusual  Unaware of surroundings and unable to respond Seizure usually lasts approximately three minutes 13

Complex Partial Seizures

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Appropriate Response – Complex Partial

 Stay calm 

Track time



Do not restrain

 Gently direct away from hazards  Remain with the individual until they have gained full awareness 15

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 16

Absence Seizures

(formerly petit mal)

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Generalized Tonic Clonic

(formerly 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 18

Generalized Tonic Clonic

(formerly grand mal)

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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 21

Call 911 if the person…

 Is injured  Has diabetes  Is pregnant  Does not resume normal breathing  Has a 1 st time seizure  Has a seizure in water 22

Treatment Options

 Medication  Brain Surgery  Diet  VNS 23

Medications

Medications are most often the first line of treatment:  Approximately 60% of people achieve seizure control after the 1 st year  15% achieve control at a later date  25% continue to have seizures despite treatment 24

Common Side Effects of Medication

 Lethargy  Weight gain / weight loss  Cognitive, concentration, memory difficulties  Hyperactivity  Emotional and/or behavioral changes 25

Brain Surgery Options

 Lobectomy • Partial Seizures • Hope for result of seizure free  Corpus Callosotomy • Generalized Seizures • Never seizure free, less frequent/ intense seizures 26

Medical Device Options

27

Special Diets



Ketogenic Diet

• Burns fat instead of glucose (fasting induced) • Gets 80% of calories from fat • Gets 20% from carbohydrates and proteins • Must be strictly managed and maintained daily – 1/3 become seizure free or almost seizure free – 1/3 improve but still have some seizures – 1/3 do not respond or find it too hard to comply 28

Special Diets

 

Modified Atkins Diet

• No fluid or calorie restriction, no protein restriction • Foods not weighed and measured, carbohydrates monitored • Not fast induced

Low Glycemic Index Treatment

• Glycemic Index: how high that food raises your blood glucose • Easier to maintain - based more on portion control • Increase of carbohydrates with a low Glycemic Index 29

Possible Impact of Epilepsy

   Depression, Anger, Anxiety, Fear Cognitive Problems Developmental Delays      Relationships Financial Costs School/Employment Driving Recreational Activities 30

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

www.efmn.org | 1600 University Avenue West, Suite 300, St. Paul, MN 55104 |

ABOUT US

 We serve Minnesota and Eastern North Dakota  Offices in St. Paul, Rochester, Duluth, St. Cloud, and Fargo  Funding Sources: used clothing, individual/corporate donations, special events and grants  The Epilepsy Foundation is the only organization in MN or ND that works exclusively with people affected by seizures.

www.efmn.org | 1600 University Avenue West, Suite 300, St. Paul, MN 55104 |

PROGRAMS THAT

EDUCATE

 Seizure Smart Communities  Seizure Recognition & Response Training  Seizure Smart Schools  Conferences & Workshops www.efmn.org | 1600 University Avenue West, Suite 300, St. Paul, MN 55104 |

PROGRAMS THAT

CONNECT

 Camp Oz  Regional Events  Shining Star Program  Information & Referral Program  Peer Groups & Online Communities www.efmn.org | 1600 University Avenue West, Suite 300, St. Paul, MN 55104 |

PROGRAMS THAT

EMPOWER

      Stroll for Epilepsy Creative Arts Advocacy Volunteering Youth Advisory Council Winning Kid www.efmn.org | 1600 University Avenue West, Suite 300, St. Paul, MN 55104 |

Make A Difference!

Help us educate, connect and empower those impacted by epilepsy! - Visit us online at www.efmn.org/giving - Participate in your employee giving campaign (United Way, Community Health Charities or Combined Federal Campaign) - Attend EFMN events - Donate your used clothing 36

Anticonvulsants and Brain Injury

Objectives

• Describe the elements of epilepsy treatment including: – Available treatments – Desired outcomes – Describe medication choices

Indications for AEDs

• • • • • • • • Epilepsy Headache Psychiatric disorders Neuropathic pain Behavior Weight loss Movement disorders Spasticity

Goals of Epilepsy Care

• • Eliminate seizures with no side effects; alternatively – Reduce the number – Decrease the severity – Minimize side effects Optimize quality of life

Chronology of AED Development Year 1912 1938 1947 1954 1960 1968 1974 1975 1978 1 st generation AEDs Drug Phenobarbital Phenytoin Mephenytoin (no longer available) Primidone Ethosuximide Diazepam Carbamazepine Clonazepam Valproate 2 nd generation AEDs Year 1993 1994 Drug Felbamate Gabapentin 1994 1996 Lamotrigine Topiramate 1997 2011 Tiagabine 1999 1999 Levetiracetam 2000 2009 Oxcarbazepine Zonisamide 2005 Pregabalin Rufinamide 2009 Vigabatrin Clobazam 3 rd generation AEDs Year Drug 2009 Lacosamide 2011 Ezogabine 2012 Perampanel

Normal CNS Function

Excitation

Glutamate Aspartate

Inhibition

GABA

Abnormal Excitation

Inhibition Glutamate Aspartate Excitation 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.

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

Drug Choices for the Treatment of New Onset Seizures

Seizure Type

Partial Onset Generalized Absence

First line therapy

Carbamazepine Gabapentin Lamotrigine Oxcarbazepine Phenobarbital Phenytoin Topiramate Valproic Acid Lamotrigine Topiramate Valproic Acid Lamotrigine Ethosuximide Valproic Acid

Medication Selection

• • • • • • • Seizure type Co-medications Medical conditions Age of the patient Insurance coverage Allergies Adherence challenges

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

Monitoring AED Treatment

• • Efficacy – Seizure control Toxicity – Side effects – Serum concentrations

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

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

Challenges in using anticonvulsants

• • • • Age Gender Illness Drug interactions

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

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

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 CYP2B6 CYP2C9 Caffeine, Theophylline Bupropion Warfarin,

Phenytoin

,

Phenobarbital

, NSAIDs CYP2C19 CYP2D6 CYP3A4 Omeprazole,

Phenytoin , S-Mephenytoin

Metoprolol, Fluoxetine Codeine, Dextromethorphan

Carbamazepine

,

Zonisamide, Tiagabine, Ethosuximde ,

Cyclosporin, Triazolam, Amlodipine, Atorvastatin, Erythromycin 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

Codeine (inactive) CYP 2D6

Morphine (active)

Approximately 7-10% of the US population is deficient in CYP 2D6 Codeine glucuronide (inactive)

As we age….

• • • • Absorption –  Blood flow to stomach and intestines – – –    acidity stomach emptying intestinal motility Distribution –  muscle –  fat Metabolism –  blood flow to liver –  size of liver Excretion –  blood flow to kidneys – –   size of kidneys ability to filter

As a result drug interactions can change over time

Summary

• • • Many medication options available Medication choice driven by several factors – Seizure type – Medical conditions – Other medications Drug interactions can usually be proactively managed

AED abbreviations Year 1 st generation AEDs Drug PB PHT PRM ESM Phenobarbital Phenytoin Primidone Ethosuximide DZP CBZ VPA Diazepam Carbamazepine Clonazepam Valproate 2 nd generation AEDs Year Drug FBM Felbamate GBP LTG Lamotrigine TPM Gabapentin Topiramate TGB Tiagabine OXC PGB Oxcarbazepine LEV Levetiracetam ZNS Zonisamide Pregabalin RUF VGB CLB Rufinamide Vigabatrin Clobazam Year LAC EZG 3 rd generation AEDs Drug Lacosamide Ezogabine