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Management of Difficult to Treat Epilepsy in Children

Management of Difficult to Treat Epilepsy in Children. Northeast Regional Epilepsy Group. Advances in the Diagnosis and Treatment of Epilepsy. Marcelo E. Lancman, M.D. Director, Epilepsy Program Northeast Regional Epilepsy Group. Advances in the Diagnosis and Treatment of Epilepsy.

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Management of Difficult to Treat Epilepsy in Children

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  1. Management of Difficult to Treat Epilepsy in Children Northeast Regional Epilepsy Group

  2. Advances in the Diagnosis and Treatment of Epilepsy Marcelo E. Lancman, M.D. Director, Epilepsy Program Northeast Regional Epilepsy Group

  3. Advances in the Diagnosis and Treatment of Epilepsy • Epilepsy concepts • Diagnosing Epilepsy • What causes Epilepsy • Treating Epilepsy • New developments

  4. Epilepsy Concepts • What is epilepsy? • What is a seizure?

  5. Epilepsy 0.5-1% Seizures 5-10% Incidence

  6. Partial Simple Complex Secondary Generalized Generalized Absence Atonic Clonic Tonic Tonic-clonic Myoclonic Classification of Seizures

  7. Classification of Epilepsy • By Localization • Partial • Generalized • By Cause • Idiopathic (unknown) • Symptomatic

  8. Classification of Epilepsy • Idiopathic Partial Epilepsy • Symptomatic Partial Epilepsy • Idiopathic Generalized Epilepsy • Symptomatic Generalized Epilepsy

  9. Idiopathic Generalized Epilepsy • Benign Neonatal Familial Epilepsy • Benign Myoclonic Epilepsy of Infancy • Generalized epilepsy with febrile seizures plus • Epilepsy with myoclonic absence • Epilepsy with myoclonic-astatic seizures • Childhood absence epilepsy • Juvenile absence epilepsy • Epilepsy with GTCS only

  10. Idiopathic Partial Epilepsy • Benign Rolandic Epilepsy • Benign Occipital Epilepsy

  11. Symptomatic Generalized Epilepsy • Infantile spasms (West syndrome) • Dravet syndrome • Lennox-Gastaut syndrome

  12. Symptomatic Partial Epilepsy • Temporal Lobe Epilepsy • Frontal Lobe Epilepsy • Parietal Lobe Epilepsy • Occipital Lobe Epilepsy • (Tuberous Sclerosis Complex, Neurofibromatosis)

  13. Special types of Epilepsy • Neonatal seizures • Landau-Kleffner syndrome • ESES (electrical status epilepticus during sleep) • Reflex Epilepsy

  14. Type of Epilepsy • The importance of knowing

  15. Diagnosis of Epilepsy • Medical History • Physical exam

  16. Testing • Testing • EEG, AEEG, VEEG • Labs • Genetics • Imaging • CT, MRI (high definition)

  17. Diagnosis • Diagnosis is clear: treatment is initiated • Diagnosis unclear: Video-EEG

  18. Video-EEG Monitoring • Continuous EEG monitoring along with continuous audio-video recording • Mostly requires inpatient admission

  19. Goals of Video-EEG Monitoring • Epilepsy vs. non-epileptic events • Characterize epilepsy type • Pre-surgical evaluation

  20. Non-Epileptic Events • 20 to 30% of patients referred with diagnosis of intractable epilepsy • Events that do not have electrical source in brain • May have physical or psychological causes that are not epilepsy • But CAN also occur in patients who have epilepsy

  21. Non-epileptic events • Physiologic (other medical conditions) • Fainting, low sugar, changes in electrolytes, toxins, fever. • Psychological • Referred to psychiatry and neuropsychologist who work with this type of stress-seizure • Psychiatric medication, psychotherapy, education

  22. Non-epileptic events • Conditions that may look like seizures: • TIAs, complicated migraines, movement disorders, sleep disorders, anxiety/panic disorder, vertigo, cardiac disorders, rage attacks, breath-holding spells,

  23. Diagnostic Advances • Magnetoencefalography

  24. What causes of Epilepsy? • The seizure threshold • Causes: • Genetics, head injury, stroke, tumors, infections, malformations, metabolic disorders (diabetes, thyroid, parathyroid, adrenal), degenerative disorders, perinatal factors and other less common (cardiac, GI, blood, inflammatory, poisons, etc)

  25. Seizure Triggers • Alcohol, stress, environmental temperature, lights, fever/illness, hormonal changes, hyperventilation, sleep deprivation, medications and supplements, missing medication doses and travel across time zones

  26. Treating Epilepsy • What is intractable epilepsy? Despite medical management, patient continues to have frequent, debilitating seizures

  27. Seizure Control

  28. Options for the Intractable Seizure Patient • Medications (combinations) • Diets • Surgical procedures • Stimulators • Resections

  29. Medications • Choices based on epilepsy type, patient profile, side effect profile, cost • Best to have patient on single antiepileptic drug (AED) • May need polytherapy (combination of medications) • Adding meds requires going up slowly with the new agent before discontinuing previous drug • Polytherapy requires deep knowledge of interactions

  30. How to use polytherapy rationally • Pharmacodynamics(what the medication does to the body) • Pharmacokinetics • (what the body does to the medications) • Absorption • Distribution • Elimination • Half life • Liver • Kidneys

  31. How to use polytherapy rationally • Side effects • Dose-related • Idiosyncratic (each person is different)

  32. Carbamazepine (Tegretol) Phenobarbital Ethosuximide (Zarontin) Phenytoin (Dilantin/Cerebyx) Valproic acid (Depakote) Primidone (Mysoline) Older Medications

  33. Gabapentin (Neurontin) Lamotrigine (Lamictal) Topiramate (Topamax) Felbamate (Felbatol) Diastat (Diazepam) Vigabatrin (Sabril) Ezogabine (Potiga) Oxcarbazepine (Trileptal) Pregabalin (Lyrica) Zonisamide (Zonegran) Levetiracetam (Keppra) Lacosamide(Vimpat) Rufinamide (Banzel) Clobazam(Onfi) Newer AED’s

  34. Medication choices based on epilepsy type…

  35. All but Zarontin and Banzel AED’s for Partial Epilepsy

  36. Best AED’s for Generalized Epilepsy • Depakote • Keppra • Lamictal • Topamax • Zonegran • Banzel

  37. Future Medications • Brivaracetam • Carisbamate • Eslicarbazepine • Ganaxalone • Losigamone • Nitrfazepam • Perampanel • Piracetam • Progabide • Remacemide • Retigabine • Seletracetam • Stiripentol

  38. What Are Some Promising New Medical Treatments? • Maintenance Treatment • Ezogabine (Potiga) • Perampanel • Vertex • Emergency Treatment • Intranasal Midazolam

  39. Potiga • Potassium Channel Opener • Partial Seizures • Rare but serious side effects

  40. Peramapanel • Glutamate Blocker • Effective in trials for partial seizures • Side effects: Dizziness, Sleepiness • Approved in Europe • Under study in US for Generalized Seizure types • Under FDA review for Partial Seizures

  41. Vx-765 for Partial Epilepsy • New approach to Epilepsy Rx • Anti-Inflammatory • Short Duration of therapy (weeks instead of years) • Oral Medicine • Early Clinical Trials Completed • Early results encouraging but longer treatment duration to be studied • Headache, dizziness, GI most common side effects

  42. Emergency Treatment • Rectal Diastat • Clinically proven • Hard to give • Adults don’t like • Can’t self administer

  43. Intranasal Midazolam • Easy to give • Preferred route • Can be self-administered or given by caretaker • Under study

  44. For patients that do not respond to medication • Ketogenic diet • Surgeries

  45. Epilepsy Surgery http://www.rch.unimelb.edu.au/cep/Media/brain/mri6.jpg http://www.fleni.org.ar/files/servicio_193_8

  46. Rates of Surgical Success* • Temporal Lobectomy 70-80% • “Lesion” Resection 70-80% • “Non-Lesional” Resection 30-50% • Medical Management 5% * Absence of Disabling Seizures

  47. Visualase • Laser Treatment • Evaluation is same as • for epilepsy surgery • No need for open brain • operation

  48. Visualase

  49. Neuromodulatory Treatments • Device implanted to alter instead of destroy brain tissue • Range of treatment possible: Electrical, Cooling, local medications • Limit body/brain side effects • Improve brain function?

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