1. The Brain and Epilepsy efmn.org

2. 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

3. 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

4. About you? Where do you work? Have you seen a seizure? efmn.org

5. 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

6. 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

7. 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

8. 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

9. 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

10. 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

11. 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

12. 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 efmn.org

13. 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

14. 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

15. 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

16. 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

17. 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

18. 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

19. 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

20. 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

21. Call 911 if the person…  Is injured  Has diabetes or is pregnant  Does not resume normal breathing or breathing stops  Has a 1 st time seizure  Has a seizure in water  Situation escalates efmn.org

22. 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 efmn.org

23. Treatment Options  Medication  Brain surgery  Medical Devices  Diet  Social and psychological support efmn.org

24. 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 efmn.org

25. Anticonvulsants and Brain Injury efmn.org

26. Objectives Describe the elements of epilepsy treatment including: – Available treatments – Desired outcomes – Describe medication choices efmn.org

27. Indications for AEDs Epilepsy Headache Psychiatric disorders Neuropathic pain Behavior Weight loss Movement disorders Spasticity efmn.org

28. 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

29. Chronology of AED Development efmn.org 2 nd generation AEDs Year Drug 1993 Felbamate 1994 Gabapentin 1994 Lamotrigine 1996 Topiramate 1997 Tiagabine 1999 Oxcarbazepine 1999 Levetiracetam 2000 Zonisamide 2005 Pregabalin 2009 Rufinamide 2009 Vigabatrin 2011Clobazam 3 rd generation AEDs Year Drug 2009Lacosamide 2011Ezogabine 2012 Perampanel

30. Normal CNS Function efmn.org Excitation Inhibition Glutamate Aspartate GABA

31. Abnormal Excitation Excitation Inhibition GABA Glutamate Aspartate 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

32. AEDs Act By Restoring Balance 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 Excitation Inhibition

33. New onset seizures efmn.org

34. Medication Selection Seizure type Co-medications Medical conditions Age of the patient Insurance coverage Allergies Adherence challenges efmn.org

35. 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

36. Monitoring AED Treatment Efficacy – Seizure control Toxicity – Side effects – Serum concentrations efmn.org

37. 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

38. 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

39. Challenges in Using AEDs Age Gender Illness Drug interactions efmn.org

40. 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

41. 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

42. http://www.cincinnatichildrens.org/svc/alpha/l/liver/liver-anatomy.htm Metabolism Changes 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

43. Major Liver Enzymes P450 EnzymeExamples of Drug That Use The Enzyme CYP1A2Caffeine, Theophylline CYP2B6Bupropion CYP2C9Warfarin, Phenytoin, Phenobarbital, NSAIDs CYP2C19Omeprazole, Phenytoin, S-Mephenytoin CYP2D6Metoprolol, Fluoxetine Codeine, Dextromethorphan CYP3A4Carbamazepine, Zonisamide, Tiagabine, Ethosuximde, Cyclosporin, Triazolam, Amlodipine, Atorvastatin, Erythromycin http://medicine.iupui.edu/flockhart/

44. Excretion http://www.nlm.nih.gov/medlineplus/ency/imagepages/1101.htm Drug is removed from the body in urine

45. Not everyone is the same No 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

46. 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

47. AED abbreviations 2 nd 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 CLBClobazam 1 st generation AEDs YearDrug PBPhenobarbital PHTPhenytoin PRMPrimidone ESMEthosuximide DZPDiazepam CBZ Carbamazepine Clonazepam VPAValproate 3 rd generation AEDs Year Drug LACLacosamide EZGEzogabine

48. Questions? Jeannine Conway Amanda Pike efmn.org