1. What to do IF Medications Fail? Dr Linda Huh Pediatric Neurologist BCCH

2. Outline and Objectives What is intractable epilepsy? What is intractable epilepsy? Discuss why medications may fail Discuss why medications may fail Learn more about alternate treatments to medications Learn more about alternate treatments to medications Epilepsy Surgery Epilepsy Surgery Vagal Nerve Stimulator Vagal Nerve Stimulator Ketogenic Diet Ketogenic Diet Discuss future potential therapies Discuss future potential therapies

3. Intractable Epilepsy 47% seizure free on first medication 47% seizure free on first medication 13% seizure free on second medication 13% seizure free on second medication <5% seizure free on third medication <5% seizure free on third medication 30% of patients have difficult to control epilepsy 30% of patients have difficult to control epilepsy

4. Intractable Epilepsy

5. Why may anticonvulsants fail? Incorrect diagnosis Incorrect diagnosis Incorrect anticonvulsant Incorrect anticonvulsant Intolerable side effects or noncompliance Intolerable side effects or noncompliance Drug-resistant epilepsy Drug-resistant epilepsy

6. Goals of Epilepsy Surgery Seizure-freedom Seizure-freedom Improvement of quality of life Improvement of quality of life Do no harm (minimize deficits) Do no harm (minimize deficits) Decrease anticonvulsants Decrease anticonvulsants

7. Aims of Epilepsy Surgery Workup Find where seizures are coming from Find where seizures are coming from To spare important brain functions To spare important brain functions

8. Evaluation for Epilepsy Surgery History and Physical Examination History and Physical Examination

9. Evaluation for Epilepsy Surgery History and Physical Examination History and Physical Examination Video EEG monitoring Video EEG monitoring

10. Evaluation for Epilepsy Surgery History and Physical Examination History and Physical Examination Video EEG monitoring Video EEG monitoring

11. Evaluation for Epilepsy Surgery History and Physical Examination History and Physical Examination Video EEG monitoring Video EEG monitoring Neuropsychological assessment Neuropsychological assessment MRI – 1.5 or 3T MRI – 1.5 or 3T

12. Evaulation for Epilepsy Surgery Ictal SPECT, PET Ictal SPECT, PET MEG MEG fMRI fMRI Wada test Wada test EcoG (electrocorticography) EcoG (electrocorticography) Subdural/Depth electrodes +/- mapping Subdural/Depth electrodes +/- mapping

13. Ictal SPECT Increased blood flow Increased blood flow

14. PET Decreased metabolism Decreased metabolism

15. Magnetoencephalogram

16. Finger Tapping- Right vs. Left q= 0.01 Right Finger Tapping Left Finger Tapping

17. Finger Tapping- Right vs. Left q= 0.01 Right Finger Tapping Left Finger Tapping

18. PRE-RESECTION - POSITION 1 8 32 529

19. What to do? Resective surgery Resective surgery Focal neocortical resection Focal neocortical resection Anteromedial temporal lobectomy Anteromedial temporal lobectomy Hemispherectomy Hemispherectomy Palliative surgery Palliative surgery Corpus callosotomy Corpus callosotomy Multiple subpial transections Multiple subpial transections Vagal nerve stimulation Vagal nerve stimulation

20. Julie Prolonged febrile seizures Prolonged febrile seizures Developed partial seizures age 9 Developed partial seizures age 9 Tried 5 medications Tried 5 medications Video EEG showed left temporal Video EEG showed left temporal MRI MRI

21. Anterior Medial Temporal Lobectomy

22. Hemispherectomy

23. Corpus Callosotomy Anterior 2/3 Full

24. Multiple Subpial Transections

25. Outcome Seizure Freedom or reduction Seizure Freedom or reduction Decrease in medications Decrease in medications Improvement in Cognition and behaviour Improvement in Cognition and behaviour Improvement in Quality of Life Improvement in Quality of Life

26. Vagus Nerve Stimulation

27. Vagal Nerve Stimulator 1997: approved by FDA (US) as adjunctive treatment of medically refractory epilepsy in adolescents and adults 1997: approved by FDA (US) as adjunctive treatment of medically refractory epilepsy in adolescents and adults 1998: approved by HPB (Canada) 1998: approved by HPB (Canada) > 40,000 patients world-wide have been implanted > 40,000 patients world-wide have been implanted

28. Indications No correlation with type of epilepsy No correlation with type of epilepsy Intractable epilepsy with no better surgical option Intractable epilepsy with no better surgical option

32. To shorten a seizure To shorten a seizure To stop a seizure To stop a seizure To decrease severity To decrease severity To shorten post-ictal phase To shorten post-ictal phase Magnet Use

33. Vagal Nerve Stimulator

34. VNS for Intractable Epilepsy 50% of patients have >50% reduction in seizures 50% of patients have >50% reduction in seizures May allow reduction in dosage of antiepileptic medications May allow reduction in dosage of antiepileptic medications Majority have improved quality of life Majority have improved quality of life Magnet use can abort seizures Magnet use can abort seizures

35. Ketogenic Diet

36. 15-35% seizure-free 15-35% seizure-free 30-50% with >90% reduction in seizures 30-50% with >90% reduction in seizures 50-75% with >50% reduction in seizures 50-75% with >50% reduction in seizures Improved alertness and development Improved alertness and development

37. Ketogenic Diet Modified Atkins Diet Modified Atkins Diet Low Glycemic Diet Low Glycemic Diet

38. Ketogenic Diet Prescribed therapy by Ketogenic Diet Team Prescribed therapy by Ketogenic Diet Team Side effects Side effects

39. Ketogenic Diet

40. Hundreds of seizures/day Hundreds of seizures/day Plateauing of development Plateauing of development > 6 medications in 6 months > 6 medications in 6 months Seizure free on the Ketogenic Diet with improvement of development Seizure free on the Ketogenic Diet with improvement of development

41. Future therapies to look to… New Anticonvulsants New Anticonvulsants Seizure prediction Seizure prediction Neurostimulation Neurostimulation Neuropace (Responsive Neuronal Stimulation) Neuropace (Responsive Neuronal Stimulation) Deep brain stimulation Deep brain stimulation Magnetic Stimulation and Cooling Magnetic Stimulation and Cooling Gene and biological agent therapy Gene and biological agent therapy

42. What can WE do when medications fail? Optimize quality of life Optimize quality of life Look for comorbidities and treat as needed Look for comorbidities and treat as needed Maintain good relationships – family and friends Maintain good relationships – family and friends Optimize school and employment Optimize school and employment Maintain a healthy lifestyle Maintain a healthy lifestyle Exercise Exercise Diet Diet Bone health Bone health

43. Thank you for your attention