Treating Intractable Pediatric

Epilepsy With the Ketogenic Diet

STEFANIE WEINER
MARCH 6, 2015

Introduction
May
2102
GBM

Dedication

Why
the
KD?
Jury is
out

Powerful

CHOP

The Plan

Anatomy &
Physiology

Epilepsy

Medical
Treatment

Medical
Nutrition
Therapy

Presentation Wrap
of Patient
Up

Anatomy & Physiology

The Brain

Anatomy & Physiology

Neuron

Synapse

Anatomy & Physiology

Seizure

physical findings or
changes in behavior that
occur after an episode of
abnormal electrical
activity in the brain

Source: MedLine Plus

http://www.nlm.nih.gov/medlineplus/ency/article/003200.htm

Types of Seizures

Focal seizures
Simple
Complex
Generalized seizures
Tonic-clonic
Clonic
Tonic

Absence
Myoclonic
Atonic

Epilepsy

Definition
History
Etiology
Diagnosis
Medical Treatment
Non-Surgical
Surgical

Definition

2+ unprovoked seizures

occurring 24+ hours apart

Diagnosis of an epilepsy

syndrome

Fisher RS. A practical definition of epilepsy. Epilepsia. 2014; 55:475-482.

Resolved if:
Past applicable age of

age-dependent
syndrome
Seizure-free for 10
years, with no seizure
medicines for the last 5
years.

Epilepsy

Migraine
Stroke
Alzheimers

2.2
million

POP QUIZ
What did
Alexander the Great, Julius
Caesar, Joan of Arc, Hndel,
Flaubert, van Gogh, and Gershwin
have in common?

History

History

1516-1520, Italy The Transfiguration by Raphael

History

Helplessness
Unpredictable

Misconception

Stigma

Etiology

Genetic

Structural/Metabolic

Unknown

Diagnosis
Clinic Visit
Medical History
Seizure History

Neurological Exam
Laboratory Results
Imaging (EEG, MRI, CT)

Diagnosis

Medical Intervention

Seizure Medications
Surgical
Resection

Disconnection

Dietary Treatment

Stimulation

NONSURGICAL

First developed 150 years ago

Seizure Medications

Source: Brodie MJ. Antiepileptic drug therapy the story so far. Seizure. 2010; 19(10):650-655.

 First line of treatment

NONSURGICAL
Seizure Medications

Side effects: weight, appetite,

dizziness, depression, sedation

Careful choice by MD

Carbamazepine
Clobazam
Clonazepam

Mechanism: neurotransmitters

Lorazepam

Diazepam Phenobarbital
Divalproex

Sodium

Felbamate
Gabapentin

Lamotrigine
Levitracetam

Phenytoin

% Seizure Control

Pregbalin
Rufinamide
Topiramate
Valproic Acid
Vigabatrin
Zonisamide

1st
2nd
3rd+
Intractable

SURGICAL
TREATMENT

Not helped by medications

Clear focal point or lesion
Success rates vs. risks

SURGICAL

Resection

Removal of seizure focus

SURGICAL

Disconnection

Disrupts seizure pathway

Corpus callostomy

SURGICAL

Hemispherectomy

Last resort
< 13 years old
Intense rehab

Vagus Nerve Stimulator

SURGICAL

Stimulation

Source: The Mayo Clinic.

http://www.mayoclinic.org/tests-procedures/vagus-nerve-stimulation/multimedia/vagus-nerve-stimulation/img-20006852

NONSURGICAL

Metabolic Changes During Starvation

Dietary Treatment

Fasting

Source: Murray RK, Granner DK, Mayes PA, Rodwell VW, eds. Harpers Biochemistry. Norwalk, CT: Appleton & Lange, 1996.

NONSURGICAL
Dietary Treatment

Fasting

Ketogenesis Pathway

NONSURGICAL
Dietary Treatment

Fasting

Metabolic Changes During Starvation

NONSURGICAL

Metabolic Changes During Starvation

Dietary Treatment

Fasting

Source: Murray RK, Granner DK, Mayes PA, Rodwell VW, eds. Harpers Biochemistry. Norwalk, CT: Appleton & Lange, 1996.

Medical Nutrition Therapy

Background
Nutrition Care Process

Assessment
Diagnosis
Intervention
Monitoring & Evaluation

MNT
Background
Dr. Russell Wilder

1921
Effects of fasting without starvation
Ketogenic
50-70% experience >50% seizure
reduction
Popular in 1920s and 1930s

MNT
Background

The Ketogenic
Diet

Ratio by weight
Total grams of fat : Total grams of protein + CHO

4:1 ratio: 90% kcal as fat

Total CHO 10 grams per day
100%
80%

55

60%
40%

15

20%

30

90

0%

Typical

Ketogenic

CHO
Protein
Fat

MNT
Background

Charlie Abrahams

Dateline 1994
1971: 2-8 articles per year
Now: 40 articles per year
The Charlie Foundation

MNT
Nutrition Care
Process

Assessment

Medical History
Diet History

Ketogenic Diet Selection

Contraindications
Growth Parameters
Energy, Protein, Fluid Needs

MNT
Nutrition Care
Process

Estimations
RDA

Assessment

Age

Kcal/kg

gm protein/kg

0-6 months

108

1.52 (AI)

WHO Equation, REE x Activity Factor

7-12 months

98

1.2

Age

Males

Females

1-3 years

102

1.05

0-3

60.9W 54

61.0W 51

4-6 years

90

0.95

3-10

22.7W + 495

22.5W + 499

7-10 years

70

0.95

10-18

17.5W + 651

12.2W + 746

11-14 years

55

0.85 (14-18)

18-30

15.3W + 679

14.7W + 496

15-18 years

45

0.85

11-14 years

47

0.85 (14-18)

15-18 years

40

0.85

Activity
Factor

Indication

1.3

Well-nourished child at bedrest with

mild/moderate stress

1.5

Normally active with mild/moderate

stress
Inactive with severe stress
Minimal activity requiring catch-up
growth

Fluid Requirements

Active requiring catch-up growth

Active with severe stress

1.7

1-10 kg

100 mL/kg

10-20 kg

1000 mL + 50 mL each kg
over 10 kg

>20 kg

1500 mL + 20 mL each kg
over 20 kg

MNT
Nutrition Care
Process

Diagnosis

Inadequate oral intake

Inadequate fat intake
Excessive carbohydrate intake
Food- and nutrition-related
knowledge deficit

MNT
Nutrition Care
Process

Intervention

Inpatient Admission
Advancement of ratio

Education
All-liquid
Parenteral administration
Supplements

MNT
Nutrition Care
Process

Intervention

MNT
Nutrition Care
Process

Intervention

MNT
Nutrition Care
Process

Intervention

GOALS
Seizure freedom/reduction
Age-appropriate weight gain
Linear growth
Increased cognition

MNT
Nutrition Care
Process

Monitoring &
Evaluation

Ketosis/Euglycemia
Other Labs

Food-Drug Interactions
Close Outpatient Follow-Up
Common Challenges
Discontinuation

MNT
Nutrition Care
Process

Monitoring &
Evaluation

Side Effects
Short Term

Long Term

Hypoglycemia

Hyperlipidemia

Acidosis

Heart disease

Dehydration

Kidney stones

Nausea/Emesis

Reflux

Diarrhea/Constipation

Linear growth failure

Lethargy

Osteoporosis

Anorexia

Vitamin deficiency

Weight loss

Pancreatitis

MNT
Nutrition Care
Process

Do kids get fat?

FAQs

High cholesterol?
How strict?

Life long?

Presentation of Patient

Meet

SP
Admitted to CHOP for Ketogenic Diet
initiation on December 8, 2014

SP
Assessment

Social History
14 3/12 year old male

Sociable
Lives at home with
mother, father, younger
brother

Special life skills class

SP
Assessment

Medical History
Followed by CHOP
Neurology since 2005
Myoclonic jerks in AM,
generalized seizure
every 2 weeks
MRI + EEG + cognitive
assessment
Generalized intractable
epilepsy and mental
retardation

SP
Assessment

Diet
History

Needs

3-day diet
record

REE =
1838 kcal

Creamy,
fatty foods

AF: 1.2-1.4

No rice,
pasta

Chocolate
milk

2205-2573
kcals per
day
Protein:
0.85
g/kg/day
Fluid: 18422456 mL/day

SP
Assessment

Medications

Labs

Klonopin
Glucose mg/dL

90

Cholesterol mg/dL

131

Triglyceride mg/dL

114

HDL Cholesterol
32 (L)
mg/dL
LDL-Cholesterol
76
mg/dL
Betahydroxybutyrate <0.30
mmol/L

Depakote

Topamax

Diastat

Tranxene

SP
Assessment

Weight
67.8 kg
75-90th %ile

120% IBW
Borderline obese

SP
Assessment

Height
170.5 cm
75th %ile

102% standard
height for age

SP
Assessment

BMI
23.32 kg/m2
85-90th %ile

SP
Assessment

Head
Circumference
56 cm

50-98th %ile

SP
Diagnosis

PES
Statement

Food- and
nutritionrelated
knowledge
deficit
related to
ketogenic
diet
initiation
as
evidenced
by need for
diet
instruction.

SP
Intervention

Meal plan
2456 kcal
Protein: 44.7 gm
CHO: 16.3 gm
Keto
Kitchen
Cooking
Demos
U Arts
Interns

Classes
Weighing
Food
Exchanges

SP
Monitoring &
Evaluation

Tolerated
advance

No N/V

Music
therapy &
video games

Complaints
of hunger
resolved

Hospital
Course

Progression
of ketosis

SP
Monitoring &
Evaluation

Ref.
Range

Dec 9
21:40

Dec 10
01:30

Glucose

70-106
mg/d

92

105

BHB

0.0-0.3
mmol/L

0.38 (H)

<0.30

Dec 10
09:00

<0.30

Dec 10
12:08

Dec 10
17:50

Dec 10
22:15

Dec 11
02:11

Dec 11
06:10

Dec 11
12:40

Dec 11
17:42

Dec 12
06:42

80

82

86

91

68 (L)

82

94

87

<0.30

1.40 (H)

1.10 (H)

1.00 (H)

1.00 (H)

1.60 (H) 0.56 (H)

Follow Up
Jan 22, 2015

No
seizures
since
1/6/15

- 1.3 kg
(2%) in
6 weeks

No
linear
growth

Struggle
to eat at
school

alert and
interactive

Summary
MERYL

Looking Ahead

Keto
Hindmilk? pill?
Asia

Other
applications

Comments

Mobile
app

Separation
from child
Dr.
Christina
Bergqvist

KD
room
service

Acknowledgements
Cagla Fenton, RD, LDN
Sue Groveman, MS, RD, LDN
Donna DiVito, RD, LDN, CNSC
Avi Weiner, DMD
Mollie & Ron Makar

Acknowledgements

References

Herculano-Houzel S. The human brain in numbers: a linearly scaled-up primate brain.

Frontiers in Human Neuroscience. 2009;3:1-11.
National Research Council. Epilepsy Across the Spectrum: Promoting Health and
Understanding. Washington, DC: The National Academies Press, 2012.
Fisher RS, Boas WvE, Blume W, et al. Epileptic Seizures and Epilepsy: Definitions Proposed by
the International League Against Epilepsy (ILAE) and the International Bureau for Epilepsy
(IBE). Epilepsia. 2005; 46:470-472.
Kwan P, Brodie M. Early identification of refractory epilepsy. The New England Journal Of
Medicine [serial online]. February 3, 2000;342(5):314-319. Available from: MEDLINE with
Full Text, Ipswich, MA. Accessed January 19, 2015.
Brodie MJ. Antiepileptic drug therapy the story so far. Seizure. 2010; 19(10):650-655
Murray RK, Granner DK, Mayes PA, Rodwell VW, eds. Harpers Biochemistry. Norwalk, CT:
Appleton & Lange, 1996.
Morris AA. Cerebral ketone body metabolism. J Inherit Metab Dis. 2005;28:109-121.
Hirtz D, Thurman DJ, Gwinn-Hardy K, et al. How common at the common neurologic
disorders? Neurology. 2007;68(5):326-337.

Wheless JW. History of the ketogenic diet. Epilepsia. 2008; (Suppl. 8):3-5. doi: 10.1111/j.15281167.2008.01821.x

Plogsted S. The Ketogenic Diet. ICAN. December 2010;2:370-376.

Zupec-Kania B, Neal E, Schultz R. An Update on Diet in Clinical Practice. Journal of Child Neurology.
Aug 2013;28:1015-1026. doi: 10.1177/0883073813487597

Questions?