Epilepsy surgery and the ketogenic diet are highly effective treatments for refractory or intractable epilepsy. Epilepsy surgery aims to remove the part of the brain responsible for seizures, requiring an extensive presurgical evaluation including EEG, MRI, PET, and neuropsychological testing to localize the seizure focus. The ketogenic diet mimics the effects of fasting to reduce seizures by producing ketone bodies from fat as an alternative fuel for the brain. It has few side effects and can eliminate seizures in over half of patients who fail drug treatments. Variants of the ketogenic diet include the modified Atkins diet and medium-chain triglyceride therapy.

1. Project CARE
Surgery and Diet for Epilepsy
Elia M Pestana Knight, MD

2. Topic today
• Surgery treatment for epilepsy
• Diet treatment for epilepsy

3. SURGERY FOR EPILEPSY

4. What is Refractory or Intractable
Epilepsy?
Definition of Refractory Epilepsy:
- Lack of acceptable seizure control
despite of
- adequate trials of appropriate drugs
- at doses or levels appropriate to
produce seizure control
- with minimal side effects

5. Impact of Intractable Epilepsy
• Quality of life (psychological, social,
occupational)
• SUDEP (sudden unexpected death in
epilepsy)
• Interictal Dysfunction
- (learning, memory, attention, etc.)
• Progressive neurological dysfunction
- Epileptic encephalopathy
• Neuropsychiatric comorbidities

6. Epilepsy Surgery
• Epilepsy surgery is a highly effective and
safe alternative for selected patients with
intractable focal epilepsy.
• Epilepsy surgeries have been performed
for more than five decades.
• Estimate of the number of appropriate
candidates far exceeds the actual referrals
to epilepsy centers.

7. Goal of epilepsy surgery
• 1. Seizure freedom
• 2. Improved quality of life for patients
and family

8. Presurgical Evaluation
• Tests and evaluations that need to be
done before the patient have epilepsy
surgery
• Why do a presurgical evaluation?
- Select the cases for surgery
- Determine the impact of the surgical
brain resection on the cognitive,
emotional state, and social situation of the
patient

9. What are some of the test done
during the presurgical evaluation?
Most important tests
• EEG and video-EEG
• Brain MRI
Additional tests
• PET scan
• Ictal SPECT
• Neuropsychological
Testing
• Tests to localize spikes
and some specific
functions: memory, motor
and language
- MEG
- fMRI
- WADA Test

10. What is an EEG?
• A diagnostic study
• Records spontaneous electrical activity
fired by the neurons in the brain
• From electrodes places in the skull or
the cranial cavity
- Surface electrodes
- Intracranial electrodes
• Subdural electrodes
• Depth electrodes

11. Who recorded the first human
EEG?
• Hans Burger (1873–
1941)
• German psychiatrist
• Recorded the first
human EEG in 1924
• Discovered the
alpha rhythm

12. Electrode Placement
10-20 system
Nz
FPz
AFz
Fz
FCz
Cz
CPz
Pz
AF3
F3
FC3
Fp1
POz
Oz
Iz
F1
FC1
C3
CP3
PO3
O1
P3
Fp2
F4
FC4
C4
P2 P4
PO4
O2
C1
CP1
P1
AF4
F2
FC2
C2
CP2 CP4
F10
FT8
F6 F8
FT10
CP6 TP8 TP10
P10
P8
P6
PO8
FC6
C6 T8 T10 A2
FC5
CP5
PO7
AF8
P7
P5
C5
AF7
F5
A1 T9 T7
TP9 TP7
P9
F7
F9
FT9
FT7
Orange
represents
the electrode
placement for
neonates
Know that electrodes T7 and T8 are label T3 and T4 in other institutions

14. Left fronto-temporal spikes

15. Right Parieto-occipital Seizure - ONSET
extra-electrodes
Ictal onset : P8, P4, O2

16. Right Parieto-occipital Seizure -
PROGRESSION

17. Right Parieto-occipital Seizure -
END

18. Brain MRI
• Recommended to be done in all patients with
new onset seizures in a non-urgent setting
• Shows abnormalities that can potentially
produce epilepsy such as:
- Mesial Temporal Sclerosis also known as
hippocampal sclerosis
- Tumors
- Vascular malformation and strokes
- Malformation of the cortical development

19. Focal Cortical
Dysplasia
09/08/06 University Hospitals Neurological Institute 19

20. PET Scan
Positron Emission Tomography
• Shows how the brain functions, specifically how
various regions of the brain utilize (metabolize)
glucose (sugar)
• It is helpful in providing additional information for
accurately locating epilepsy in a specific region of
the brain
• Requires the injection of a radiotracer (substance
that has been radiolabeled so it can be identified
when the patient is in the scan)

21. PET scan

22. Ictal SPECT Scan
Single Photon Emission Computed
Tomography
• Shows how the brain functions before
(interictal) and during the seizure (ictal)
• Useful for the detection of the focus that
generates the seizures
• Measures the relative blood flow in
various regions of the brain at a specific
moment in time.
• Requires the injection of a radiotracer
(substance that has been radiolabeled so
it can be identified when the patient is in
the scan)

23. Ictal SPECT

24. Neuropsychological Testing
• Identifies cognitive weakness correlating
it with areas of brain dysfunction or
seizure onset
• Identifies the functional capacity of
patients
• Predicts neurosurgical outcomes, risk for
changes after the surgery, i.e. memory
dysfunction, cognitive changes, etc.

25. Other complementary tests
TESTS TO LOCALIZE SPIKES AND
SOME SPECIFIC FUNCTIONS:
MEMORY, MOTOR AND
LANGUAGE

26. MEG
Magnetoencephalography
• Measures the magnetic field generated
by electric current within the brain
neurons
• EEG and MEG are complementary and
can be recorded simultaneously
• useful mainly for interictal recording
• not available in all centers
• requires patient cooperation

27. Interictal Spike Recording with
Cluster of interictal epileptic spikes
spike
MEG
Tim Roberts, CHOP; formerly University of Toronto and UCSF

28. fMRI (functional MRI)
• Used to map language, motor function,
and interictal spikes
• Localizes those areas by looking at the
difference oxygenated and
deoxygenated hemoglobin before and
during specific activation task
• Requires active cooperation of the
patient
• Not available in all center

29. fMRI – Motor task

30. fMRI – Language and memory
Language task Memory task

31. The Wada Test
Intracarotid Amobarbital
Procedure
• is named after the Japanese physician
who first performed it, Dr. Jun Wada
• used to localize language and memory
• it is an invasive procedure meaning
that patient will need anesthesia and
femoral artery access to reach the
internal carotid artery
• requires patient cooperation

32. DIET FOR EPILEPSY

33. When do we use ketogenic diet:
• Patient has failed more than 2 antiepileptic
medications
• Patient is not a surgical candidate
• Patient has generalized epilepsy, in
particular myoclonic
• Patient has epileptic encephalopathy
• Don’t Miss –
- Glut 1 deficiency
- Pyruvate dehydrogenase deficiency
Livingston S. et al. Ketogenic diet in the treatment of childhood epilepsy.
Dev Med Child Neurol. 1977;19;833-834

34. KG Diet for some specific
Epilepsy Syndromes
• Early infantile epileptic encephalopathy
(Ohtahara Syndrome)
• Early myoclonic epilepsy
• Myoclonic absence epilepsy
• Lennox—Gastaut
• Myoclonic—Astatic Epilepsy (Doose
syndrome)
• Severe myoclonic epilepsy in infancy (Dravet
syndrome)
• Rett Syndrome
• Tuberous Sclerosis Syndrome

35. Other benefits of the Ketogenic Diet
• Weight loss
• Potential to reduce medication dosages or
number
• 20% of patients are able to discontinue
medications over time
• Improvements in behavior and development
• Potential for long term
neuroprotective/antiepileptogenic process
• Of those who achieved seizure freedom, up
to 80% remain seizure free once off the diet
(after 2 years) (Marsh EB, et al. Epilepsia. 2006;
47(2):425-430)

36. Other uses of ketogenic diet
Kossoff, EH. Ketogenic Diets: an update for child neurologists. J. Child Neurology.
2009;24(8)979-988.

37. • Kossoff, EH. Ketogenic Diets: an
update for child neurologists. J. Child
Neurology. 2009;24(8)979-988.

38. Epilepsy and Diet
Historical Aspects
• There are multiple ancient references to
starvation or diet alteration in the treatment of
epilepsy
- Dating back to 400 BC and include Hippocrates,
Galen and Erasistratus
• “One inclining to epilepsy should be made to fast without
mercy and be put on short rations”

39. Epilepsy and Diet
Historical Aspects
• The middle ages: ‘the Falling Sickness’
Possession
Falling Evil
Lunacy
Rational <-> Superstitious
Magical <-> Religious
Diets,
Drugs,
Remedies:
Blood,
bones,
plants,
precious
stones
Amulets,
Observing
the moon,
Prayer to
God
Fasting

40. Epilepsy and Diet
Historical Aspects
• First modern study of fasting was
in France in 1911
- 20 patients ate a low calorie,
vegetarian diet alternating
with fasting and purging
- 2 benefited, the other 18
were unable to maintain
compliance
- All reported an increase in
mental capacities, as
compared to their
potassium bromide

41. Epilepsy and Diet
Historical Aspects
• In 1925 Wilder and Peterman released data
on children:
- 95% of 37 children had improved seizure
control, 60% were seizure free
• By 1930 it had been studied on 100 teens
and adults
- 56% of 100 improved, 12% were seizure free
- This was the last study of ketogenic diet use in
adults with epilepsy until 1999

42. Epilepsy and Diet
Historical Aspects
• In the 1920’s and 30’s the diet was widely
used due to limited drug options:
bromides (1857) and Phenobarbital (1912)
• With the discovery of phenytoin (1938)
and subsequently valproic acid (1970’s),
the use of the diet declined
• The first randomized controlled trial was
published in 2008, 87 years after its
introduction
Neal, EG, et al. The ketogenic diet for the treatment of childhood epilepsy:
a randomized controlled trial. Lancet Neurol. 2008;7(6):471-472.

43. How the ketogenic diet
works?
• The exact mechanism of action is
unknown

44. What is the efficacy of the
ketogenic diet?
• 58% seizure free
• 35% with >50% reduction

45. Ketogenic Diet
Implementation
• Two approaches:
- Traditional approach:
• complete fast for up to two days (historically with
fluid restriction)
- New approach:
• immediate initiation of the diet at a reduced
concentration

46. Ketogenic Diet Prescription
• Ratio 3: 1 or 4:1

49. Ketocal
Energy Distribution:
Protein 8.2% Carbohydrate 3.1% Fiber1.5% Fat (LCT 100%)90%

50. Ketogenic Diet—Adverse
Effects
• Patients have reported a consistently reduced quantity of bone
mass
- Improves with Vitamin D 5000 IU/day
- Especially significant in those who remain on high risk AED’s
• Kidney stones 6-10%%
• GI symptoms, constipation, nausea, vomiting, abdominal pain
• Elevated lipids (typically transient) and without long term
complications
• Thinning of hair and (rarely) alopecia can occur
• Growth retardation
• Carnitine deficiency
• Severe low protein in body
• Elevations in liver function tests (typically with concurrent
medication with VPA)
• Bilateral optic neuropathy (improved with Vitamin B
supplementation)

51. Medications to discuss with your
doctor due to Potential Adverse
Drug Reactions
• Medical suspensions: Have sugars added
• Children’s Tylenol has 1g per 0.8mls
• Acetazolamide and topiramate
• Valproate: elevated liver enzymes
• Phenobarbital: serum concentration increases in acidotic
state
• Carnitine is not contraindicated, but interferes with ketone
production
• Others: toothpastes, sunscreens, lotions, shampoo

52. When to stop the ketogenic
diet?
• Diet has been ineffective after 2-3 months
of trial with documentation of ketosis
• Patient is having undesirable side effects

53. Think about the ketogenic diet
as another antiseizure
medication
• The diet needs to be stopped gradually
(wean)
• Consumption of glucose or
administration of glucose in fluids can
result in break though seizures

54. Other diet modalities used in
epilepsy

55. Variant Ketogenic Diets

56. Dietary Therapies Other than
Classical Ketogenic Diet
• Low Glycemic Index treatment (Smart Carbohydrate intake)
- Works around theory that ketogenic diet may work in part because of
stable, lower serum glucose
- Goal is not ketosis, but chronic stable low glucose
- Remains a high fat diet (60%) but allows most carbohydrates of all the
diets (40-60g/d).
• Carbs must have a glycemic index under 50
• 1:1 ratio
- Foods are estimated
- Diet is started at home
- Short term results indicate a 50% reduction in seizure frequency with
figures approaching the KD.
- Side effect profile is reduced and meals are more palatable and
tolerated
- Use of the glycemic index is good for heart health, diabetes

57. Modified Atkins (Carbohydrate-only
restriction)
• Modified Atkins (Carbohydrate-only
restriction)
- Developed at Johns Hopkins after Epilepsy
patients reported in improvement in seizure
frequency with induction on Adkins diet
- Modified diet’s goal changed from weight loss
to continuous induction phase (prolonged
ketosis) and encouraged fat consumption
(65% of calories)
- Less severe dietary restrictions, with no limit
on calories or protein and a loose ratio of 1:1,
foods are “estimated”

58. Modified Atkins (Carbohydrate-only
restriction)
- All carbohydrate types are allowed and can
be given all at once
- 10g carbohydrate for children/20g for
adults, but may liberalize in 1-3 months to
20-30g/d based on seizure control
- Still require vitamin supplementation
- Few side effects, but cholesterol is
increased, and it is a newer diet
- Does not require an hospitalization but
routine monitoring is still required

59. Medium Chain Triglyceride
Therapy
- A new spin on the Classic ketogenic diet,
which based on Long chain (13-21
carbons) triglyceride therapy
- Produce more ketones than LCT’s
- Allows a reduction in calories from fat, and
increment the amount of carbohydrates in
diet (approx. 1:1 ratio of F:P+C)
- Some investigators have found this to be
less efficacious than the classic ketogenic
diet, but this is inconsistent in studies and
likely patient dependent
- Side effects: abdominal cramps, diarrhea
and vomiting

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