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Non-pharmacological therapies for Lennox-Gastaut Syndrome


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Kelly Knupp, MD, discusses non-pharmacological therapies for Lennox-Gastaut Syndrome

Published in: Health & Medicine
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Non-pharmacological therapies for Lennox-Gastaut Syndrome

  1. 1. Non-Pharmacologic Therapies: What next? Kelly G Knupp, MD MSCS FAES Associate Professor of Pediatrics and Neurology University of Colorado
  2. 2. Non Medication Treatments • Ketogenic diet • Vagal nerve stimulation • Epilepsy surgery • Other options
  3. 3. Ketogenic Diet • Starvation: produces ketone bodies which have AED effect and diet continues ketosis  allows adequate amount of calories and protein to grow • Unknown mechanism • Two types: Cream and MCT oil • Used in children more than adults: compliance • Useful with all seizures: especially tonic, atonic, atypical seizures, less for partial seizures • Efficacy: 7% seizure free, 20% greater than 90% reduction in seizures, 50% with reduction of more than 50% in seizure frequency after 1yr (Johns Hopkins 1997)
  4. 4. Sample Diets • Breakfast:  Scrambled eggs with butter  Diluted cream  Orange juice • Lunch  Spaghetti squash with Parmesan and butter  Lettuce leaf with mayonnaise  Orange diet soda with whipped cream • Dinner  Hot dog slices with sugar free ketchup  Asparagus with butter  Chopped lettuce with mayo  Sugar free vanilla popsicles • Egg nog as replacement
  5. 5. Ketogenic Diet
  6. 6. Acute Adverse Effects  Hunger  Hypoglycemia  Drowsiness, lethargy, irritability  Nausea, vomiting • Low blood sugar or ketone build-up(ketosis)  Dehydration • If child refuses to drink enough fluids  Excessive ketosis (acidosis)  Refusal to eat
  7. 7. Chronic Adverse Effects • Refusal to eat • Hyperlipidemia  Cholesterol &triglycerides • Low free & total carnitine • Constipation or diarrhea • Zn deficiency: hair thinning and loss • Acidosis • Hyperuricemia • Hypocalcemia • Suboptimal growth:  Vining 2002: 237 children small decrease in scores with larger changes by 2yr
  8. 8. Potentially Serious Or Life- Threatening Effects • Kidney stones 5-8% • EKG changes - Prolonged QT interval • Increased bruising with bleeding • Pancreatitis • Immunosuppression
  9. 9. Vagus Nerve Stimulation
  10. 10. Vagus Nerve Stimulation • A pacemaker like device where implanted in the left chest wall and stimulates a nerve in the neck (vagus nerve) that stops seizures • Has a baseline stimulation that the doctor sets but also has a magnet where it can be swiped over the device to make it go quicker  Useful in cases where patient has chronic intractable seizures and will stop prolonged seizures or clusters of seizures and prevent use of rectal diazepam  Also helpful for auras to prevent spread • Maybe longer efficacy time of 18 months • Some use currently for depression as well • Unknown mechanism of action
  11. 11. VNS: pulse generator and lead and magnet
  12. 12. VNS placement
  13. 13. Side Effects Of VNS • May include:  Temporary hoarseness/changes in voice tone  Cough  Tickling in the throat  Shortness of breath  Surgery: vocal cord paralysis and infection 1% • Generally occur during the stimulation periods • Typically decrease over time
  14. 14. Epilepsy Surgery in Pediatrics
  15. 15. Epilepsy Surgery • Used for focal epilepsies:  temporal lobectomy  extratemporal resection  hemispherectomy  Not usually used for generalized seizures unless corpus callosotomy • Estimated as many as 5000 new patients annually in the US might benefit from epilepsy surgery but only 1/3 receive treatment
  16. 16. Types Of Epilepsy Surgery • Focal:  Lesionectomy  Lobectomy  Corticectomy  multiple subpial transection • Generalized: corpus callosotomy for drop seizures or tonic seizures • Multilobar or hemispherectomy
  17. 17. Corpus Callosotomy
  18. 18. Anatomic Hemispherectomy
  19. 19. Epilepsy Surgery Candidates • Drug resistant epilepsy • failed at least 3 AED, one of which is new • If the patients’ development status is regressing rapidly  issues to cerebral plasticity in children where more functional recovery if performed early • Presence of lesion or single focus where not critical for function (i.e. motor, language and vision) • Predominant seizure type and frequency
  20. 20. Sequence Of Evaluation For Surgery • Need to go to an established pediatric epilepsy surgery center • Admission for videotelemetry: need to capture 2-3 seizures to make sure that it is coming from one location  Sometimes need to wean meds to provoke seizure • MRI with thin cuts • PET or SPECT: functional neuroimaging  PET is where put in radioactive sugar tracer and areas where the seizure starts do not metabolize sugar well and light up. Needs to be not seizing  SPECT: tracer for cerebral blood flow and with active seizure, area where onset has most blood flow. Needs to be seizing and injected within 30 seconds of start of seizure
  21. 21. FDG-PET in TLE
  22. 22. Other Testing Outside Of Surgery Phase I Evaluation • MEG: for motor control and localization • DTI: for localization • Functional MRI: for language location • SPECT: for localization • Neuropsychological testing: language and memory • Wada: for language and memory dominance • Intraoperative: ECoG, SSEP and grids
  23. 23. PMT SEEG electrodes 3.5 mm interelectrode distance RIGHT ROF (1x16) RAmy (1x12) RHip (1x12) RTO (1x16) RPA (1x16) RPP (1x10) ROcc (1x12) RIght Orbitofrontal ROF 1x16 - 8585 Right Hippocampus RHip 1x12 - 10271 Right Temporo-Occipital RTO 1x16 - 8584 Right Amygdala RAmy 1x12 - 10272 Right Occipital ROcc 1x12 - 10214 Right Parietal Ant RPA 1x16 - 8590 Right Parietal Posterior RPP 1x10 - 8431 ANT POS T RPP RPA ROcc RTO RHip RAmy RFO
  24. 24. Surgery Several case reports and small series demonstrate seizure freedom after surgery Can be as high as 60% in some series Younger age of surgery likely leads to more improvement in cognition
  25. 25. 9 yo with LGS Seizures started at 3 years of age 1. bilateral arm stiffening 4-5/ day 2. Staring with lip smacking and wandering lasting up to 2 minutes, rarely will evolve to generalized tonic seizures 1-2 times a week EEG consistent with LGS Normal development until 3 ½ then stopped gaining skills
  26. 26. Imaging
  27. 27. Imaging Abnormality removed with surgery!
  28. 28. Follow up 2 seizures after surgery EEG Week of surgery still with slow spike and wave 3 months later – no epileptiform discharges Gradually making more gains in school. Now reading Able to write name Performing math Now Seizure Free!
  29. 29. Laser Surgery
  30. 30. Other “Non-pharmacologic” Options • N-acetyl cysteine • Tumeric • CBD • Bromides • Carnitine • Vit D • Vit E • Pyridoxine
  31. 31. Clinical Evidence: Retrospective study • N = 75 (average age 7y)  1/3 report a 50% reduction in seizures  Response rate similar with all products  Families that moved from out of state 2x more likely to report an improvement  Response rate varied by syndrome LGS>Dravet  11 patients (15%) discontinued treatment, largely due to inefficacy  2 patients seizure free Press, C Epilepsy & Behavior 2015
  32. 32. Conclusion • There are always more options • Talk to your provider • Get a second opinion if needed