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

1. Non-Pharmacologic
Therapies: What next?
Kelly G Knupp, MD MSCS FAES
Associate Professor of Pediatrics
and Neurology
University of Colorado

2. Non Medication Treatments
• Ketogenic diet
• Vagal nerve stimulation
• Epilepsy surgery
• Other options

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. 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. Ketogenic Diet
http://www.msnbc.com/news/1964640.jpg

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. 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. Potentially Serious Or Life-
Threatening Effects
• Kidney stones 5-8%
• EKG changes - Prolonged QT interval
• Increased bruising with bleeding
• Pancreatitis
• Immunosuppression

10. Vagus Nerve Stimulation

11. 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

12. VNS: pulse generator and
lead and magnet

13. VNS placement

14. 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

15. Epilepsy Surgery in
Pediatrics

16. 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

17. Types Of Epilepsy Surgery
• Focal:
 Lesionectomy
 Lobectomy
 Corticectomy
 multiple subpial transection
• Generalized: corpus callosotomy for drop
seizures or tonic seizures
• Multilobar or hemispherectomy

18. Corpus Callosotomy

19. Anatomic Hemispherectomy

20. 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

21. 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

23. FDG-PET in TLE

24. 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

26. 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

28. 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

29. 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

30. Imaging

31. Imaging
Abnormality removed with surgery!

32. 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!

33. Laser Surgery

34. Other “Non-pharmacologic”
Options
• N-acetyl cysteine
• Tumeric
• CBD
• Bromides
• Carnitine
• Vit D
• Vit E
• Pyridoxine

35. 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

36. Conclusion
• There are always more options
• Talk to your provider
• Get a second opinion if needed