Project CARE

Surgery and Diet for Epilepsy

Elia M Pestana Knight, MD

Topic today

• Surgery treatment for epilepsy

• Diet treatment for epilepsy

SURGERY FOR EPILEPSY

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

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

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.

Goal of epilepsy surgery

• 1. Seizure freedom

• 2. Improved quality of life for patients

and family

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

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

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

Who recorded the first human

EEG?

• Hans Burger (1873–

1941)

• German psychiatrist

• Recorded the first

human EEG in 1924

• Discovered the

alpha rhythm

Electrode Placement10-20 system

Nz

FPz

AFz

Fz

FCz

Cz

CPz

Pz

FC3

F3

AF3

Fp1

Iz

Oz

POz

FC1

F1

O1

PO3

P3

CP3

C3

P2 P4

PO4

O2

C1

CP1

P1

AF4

Fp2

F2

FC2

C2

CP2 CP4

C4

FC4

F4

CP6 TP8 TP10

P10

P8P6

PO8

FC6

C6 T8 A2T10

FT8

F10

F8F6

FT10

PO7

AF8

P7P5

CP5

C5

FC5

AF7

F5

T9A1 T7

TP9 TP7

P9

F7

F9

FT9FT7

Know that electrodes T7 and T8 are label T3 and T4 in other institutions

Orange

represents

the electrode

placement for

neonates

Left fronto-temporal spikes

Right Parieto-occipital Seizure - ONSETextra-electrodes

Ictal onset : P8, P4, O2

Right Parieto-occipital Seizure -

PROGRESSION

Right Parieto-occipital Seizure -

END

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

09/08/06 University Hospitals Neurological Institute 19

Focal Cortical

Dysplasia

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)

PET scan

Ictal SPECT ScanSingle 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)

Ictal SPECT

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.

TESTS TO LOCALIZE SPIKES AND

SOME SPECIFIC FUNCTIONS:

MEMORY, MOTOR AND

LANGUAGE

Other complementary tests

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

Cluster of interictal epileptic spikes

spike

Interictal Spike Recording with

MEG

Tim Roberts, CHOP; formerly University of Toronto and UCSF

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

fMRI – Motor task

fMRI – Language and memory

Language task Memory task

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

DIET FOR EPILEPSY

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

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

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)

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”

Epilepsy and Diet

Historical Aspects

• The middle ages: ‘the Falling Sickness’

Possession

Falling Evil

Lunacy

Diets,

Drugs,

Rational <-> Superstitious

Magical <-> Religious

Remedies:

Blood,

bones,

plants,

precious

stones

Amulets,

Observing

the moon,

Prayer to

God

Fasting

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

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

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

introductionNeal, EG, et al. The ketogenic diet for the treatment of childhood epilepsy:

a randomized controlled trial. Lancet Neurol. 2008;7(6):471-472.

How the ketogenic diet

works?

• The exact mechanism of action is unknown

What is the efficacy of the

ketogenic diet?

• 58% seizure free

• 35% with >50% reduction

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

Ketogenic Diet Prescription

• Ratio 3: 1 or 4:1

Ketocal

Energy Distribution:

Protein 8.2% Carbohydrate 3.1% Fiber1.5% Fat (LCT 100%)90%

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)

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

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

Think about the ketogenic diet

as another antiseizure

medication

• The diet needs to be stopped gradually

(wean)

• Consumption of sugar or administration

of glucose in fluids can result in break

though seizures

Other diet modalities used in

epilepsy

Variant Ketogenic Diets

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

• 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”

Modified Atkins (Carbohydrate-only

restriction)

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

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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