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Overview of Epilepsy

Hackensack University Medical Center Comprehensive Epilepsy Center. Overview of Epilepsy. Georges A. Ghacibeh, MD, MS. A transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain

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Overview of Epilepsy

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  1. Hackensack University Medical Center Comprehensive Epilepsy Center Overview of Epilepsy Georges A. Ghacibeh, MD, MS

  2. A transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain Incidence: approximately 80/100,000 per year Lifetime prevalence: 9% (1/3 benign febrile convulsions) Seizures vs. Epilepsy SeizuresEpilepsy A disorder of the brain characterized by an enduring predisposition to generate epileptic seizures and by the neurobiologic, cognitive, psychological, and social consequences of this condition Incidence: approximately 45/100,000 per year Point prevalence: 0.5-1% (2.5 million) Cumulative risk of epilepsy: 1.3% - 3.1%

  3. Definition: Seizure vs. Epilepsy Sz Sz Diagnosis Seizure-free No Sz Epilepsy Treatment No Epilepsy Stop Treatment

  4. Classification of Seizures Focal - Onset • Simple partial • Complex partial • Secondarily generalized Generalized - Onset • Absence • Myoclonic • Generalized tonic-clonic • Tonic • Clonic • Atonic

  5. Seizure Types Generalized Focal Focus

  6. Classification of Epilepsy Etiology Primary Secondary Generalized Seizure Onset Focal

  7. Epidemiology of Epilepsy Epilepsy: Incidence Rates by Seizure Type* *Data from Rochester, Minn (1935-1979). Adapted with permission from Annegers JF. In: The Treatment of Epilepsy: Principles and Practice. 2nd ed. Baltimore, Md: Williams & Wilkins; 1997:165-172.

  8. Seizure Risk Factor • Prenatal and Birth Injury • Febrile Convulsions • Developmental Delay • Head Trauma • CNS Infections • Brain Tumors • Brain Surgery • Family History

  9. Evaluation and Diagnosis • History from patient and family • EEG: standard 20-30 minutes • EEG Monitoring: • Ambulatory EEG • Video EEG • Neuroimaging

  10. The Tracing

  11. Video-EEG Monitoring • Continuous synchronized EEG and Video recording • Monitors patient’s behavior and EEG • Scalp: Electrodes Similar to EEG • Invasive: Electrodes within or on the surface of the brain.

  12. Paroxysmal Events • Epileptic • Focal (Partial) onset • Generalized onset • Non-Epileptic: • Psychogenic • Cardiac • Vasovagal • Sleep disorder • Migraine…

  13. Partial (focal) Seizures • Simple Partial Seizure • no loss of awareness • Complex Partial Seizure • Impaired consciousness w w/o aura • Clinical manifestations vary with origin & degree of spread • Clinical Manifestations: • Automatisms (manual, oral) • Bicycling and fencing posture (frontal) • Duration (typically 30 seconds to 3 minutes) • Amnesia for event • Partial Seizure with Secondary Generalization

  14. Primarily Generalized Seizures • Absence: Brief staring (<30sec ) • Myoclonic: Brief, shock-like muscle contractions • Atonic: Loss of muscle tone • Tonic: Sustained muscle contraction • Tonic-Clonic

  15. Non-Epileptic Events • Psychogenic • Cardiovascular • Syncope • Metabolic (glucose, Na, Ca, Mg) • Sleep disorders (parasomnias, cataplexy)

  16. New Onset Seizure • After the first seizure, no clear indication for treatment • Routine EEG is usually of low yield • Long term EEG monitoring is sometimes indicated to determine need for long term treatment with AEDs.

  17. What Type of Seizure was it? Type Recurrence Risk (2 years) Provoked, no brain injury 3% Provoked, brain injury 10% Single, Unprovoked 42% Recurrent, Unprovoked 70-80% Pohlmann-Eden, BMJ, 2006.

  18. Discontinue AEDs • Patients who are seizure-free for over 2 years wanting to come-off AEDs • Monitoring for 48 – 72 hourse OFF anti-epileptic drugs • Seizure activity (spikes) on EEG indicate high risk of seizure recurrence.

  19. Treatment of Epilepsy • Medications • Diet Therapy • Hormonal Therapy • Surgical: • Resective • Multiple Subpial Transaction • Vagus Nerve Stimulator • Experimental: • Deep Brain Stimulation • Radiosurgery • Cortical Stimulation

  20. Anti-Epileptic Drugs (AED) • A drug that decreases the frequency and/or severity of seizures in patients with epilepsy • Treats the symptom of seizures, not the underlying epileptic condition • Goal—maximize quality of life by minimizing seizures and adverse drug effects

  21. Available AEDs • Phenobarbital • Mysoline  Primidone • Dilantin phenytoin • Tegretolcarbamazepine • Depakotevalproic acid • Zorantinethosuxamide • Felbatolfelbamate • Neurontingabapentin • Lamictallamotrigine • Topamaxtopiramate • Gabitriltiagabine • Trileptaloxcarbazepine • Zonegran zonisamide • Keppralevetiracetam • Lyrica pregabaline • Frisium  clobazam • Klonopin  clonazepam • Tranxene  chlorazepate • Banzel  rufinamide • Vimpat  lacosamide

  22. Rational Use of AEDs • Indication / Guidelines by FDA, AES, AAN • Seizure type/ Epilepsy syndrome • Adverse effects (acute; chronic) • Comorbid conditions • Cost • Age • Gender • Concomitant medications • Social factors • Pharmacokinetic profile

  23. Rational Use of AEDs Dilantin Phenobarbital Mysoline Tegretol Depakote Zorantin Felbatol Neurontin Lamictal Topamax Gabitril Trileptal Zonegran Keppra Lyrica Frisium Klonopin Tranxene Banzel Vimpat Side Effects Co-morbid Conditions Sleepiness Cognitive Behavioral Metabolic : Liver Electrolytes Hyperthermia Weight gain Ostioporosis Bone Marrow Co-TRT Avoid Migraine Pain Mood Kidney Stones Psychiatric Liver Disease Bone Marrow Drug Interactions Cytochrome P-450: Steroids Chemotherapy Coumadin Many others… Age / Sex Young Women Elderly

  24. FDA: Use of AEDs

  25. AED Treatment Options Partial Generalized Simple Complex SecondaryGeneralized Tonic-Clonic Tonic Atonic Myoclonic InfantileSpasms Absence Rufinamide ACTHTPMTGBVGB PHT, CBZ, GBP, OXC, TGB, LCS PGB ESX VPA, LTG, TPM, ZNS, LVT, FBM

  26. AED Therapy Epilepsy Time First AED Increase Dosage Switch AED Combine AEDs Polytherapy Trial and Error Method

  27. Trial and Error Method TRIAL ERROR Adjust Dosage Recurrent Seizures Change AED Combine AEDs Side Effects

  28. Rational Use of AEDs PharMetrics. April 2002 to June 2003 IMS NPA, Dec 2003. Kwan P, Brodie MJ. N Engl J Med 2000; 342: 314-9.

  29. Success With Antiepileptic Drugs Previously Untreated Epilepsy Patients (N=470) Kwan P, Brodie MJ. N Engl J Med. 2000;342(5):314-319

  30. Common Side Effects • Dizziness • Sleepiness • Drowsiness • Ataxia • Blurred vision

  31. Diet Therapy

  32. Energy Source: Regular Diet Carbohydrates Fat Glucose Fatty Acids Brain Body

  33. Energy Source: Ketogenic Diet Carbohydrates Fat Ketones Fatty Acids Brain Body

  34. Ketogenic Diet • Very High Fat, Low Carbohydate And Protein Diet • Fat Used As Alternative Energy Source • Goal = Ketosis • Why? • Elevated Ketones Correlate With Optimal Seizure Control • Fluid And Calorie Restricted • Based On Ratio – 3:1 or 4:1 • Food Must Be Weighed

  35. Ketogenic Diet • Admission to the hospital 3-5 days • Precise amounts of carbohydrates, proteins and fat • All food needs to be weighed • Strict monitoring of urine ketones and blood work • All medications, including over-the-counter medications, such as Motrin and Tylenol have to be keto-friendly

  36. Modified Atkins Diet • Easier than the ketogenic diet • Many advantages over ketogenic diet: • No admission to the hospital • Only carbohydrates are measured and restricted • Start at 10 gm per day, then increase to 15-20 gm per day • No Protein Restriction • No Fluid Restriction • No Weighing Food • www.atkinsforseizures.com

  37. Compare And Contrast

  38. Low Glycemic Index Diet • No Hospital Admission Required • Allowance: 40 – 60 grams CHO/day • Only Foods With Low Glycemic Index are allowed • Foods quantities are not weighed but are based on portion size • More Flexible Lifestyle

  39. Hormone Therapies • Some women experience increase in seizure frequency around their menstrual period • Catamenial seizures • This is believed to be due to sudden changes in levels of hormones • There are three types of catamenial seizures

  40. Menstrual Cycle Estradiolg/mL E2 P Progesterone ng/mL 150 30 25 100 20 Serum Hormone Levels 15 50 10 5 0 1 3 5 7 9 11 13 15 17 19 21 23 25 27 Day of the Cycle E2 = estradiol; P = progesterone.

  41. Normal Cycle: Seizures More Frequent With Drop in Progesterone (C1) or With Estrogen Surge (C2) Estradiol g/mL E2 P Progesterone ng/mL 150 30 C2 C1 25 100 20 Serum Hormone Levels 15 50 10 5 0 1 3 5 7 9 11 13 15 17 19 21 23 25 27 Day of the Cycle C1 = catamenial 1 (seizure pattern); C2 = catamenial 2; E2 = estradiol; P = progesterone. Herzog AG, et al. Epilepsia. 1997;38:1082-1088.

  42. E2 P Estradiol g/mL 100 25 Progesterone ng/mL C3 80 20 60 15 Serum Hormone Levels 40 10 20 5 0 1 3 5 7 9 11 13 15 17 19 21 23 25 27 Day of the Cycle Inadequate Luteal Phase Cycle C3 = catamenial 3. Herzog AG, et al. Epilepsia. 1997;38:1082-1088.

  43. Catamenial Epilepsy • Katamenios = “monthly” • The tendency for increased seizures related to the menstrual cycle • Affects 30%-40% of women with epilepsy Note: Catamenial seizure patterns will be apparent only during ovulatory cycles, and 30% of cycles in women with epilepsy are anovulatory • Herzog AG, et al. Epilepsia. 1997;38:1082-1088.

  44. Hormone Therapy • Supplementation of Progesterone during the period of increased seizures is effective in reducing seizures • Oral natural progesterone is the most effective • Give for 7 days starting on day 23 of the cycle • Treatment with intramuscular progesterone is sometimes effective (Depo-Provera) • Some seizure medications shorten the half-life of Depo-Provera and more frequent injections are necessary (every 10 or 8 weeks instead of every 12 weeks)

  45. Herbal Medicines • No proven benefits in epilepsy • Some herbal medicines may increase the risk of seizures • Some herbal medicines may interact with seizure medications • If you plan on trying an herbal medicine, first research it thoroughly and consult with your doctor • NEVER substitute an herbal medicine for your regular seizure medications • http://www.mskcc.org/mskcc/html/11570.cfm

  46. Herbal Medicines Some Herbal Substances Used In • Anxiety • Depression • Low Energy • Arthritis • Memory difficulties • Borage • Caffeine • Chamomile • Ephedra • Evening Primrose • Ginkgo • Ginseng • Herbal Essential Oils • Kava • Passionflower • St. John's Wort • Valerian • Some may cause seizures • Some may have bad interactions with seizure medications or other medications Caution

  47. Supplements • Vitamins: A - E • Minerals: Magnesium, Selenium, Zinc… • Other: CoQ10, Carnitine, anti-oxidants, …

  48. Supplements: The Rule • Most supplements are probably safe if taken at the recommended dose • No proven efficacy in treating seizures • BUT: Some supplements are recommended in certain metabolic disorders affecting the function of the mitochondria

  49. Mitochondria Mitochondria are small organelles inside the cells, including the brain cells. Their function is to generate energy for the cell

  50. Mitochondria and Seizures • Certain mitochondrial diseases can cause seizures • It is possible that some patients with epilepsy might have an un-diagnosed mitochondrial disease as a cause of their seizures • It is not know if repeated seizures exhaust the energy source of the brain and lead to mitochondrial dysfunction

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