S T E F A N I E W E I N E R

M A R C H 6 , 2 0 1 5

Treating Intractable Pediatric Epilepsy With the Ketogenic Diet

Introduction

Why the

KD?

May 2102

GBM

Jury is out

CHOP

Powerful

Dedication

The Plan

Wrap Up

Presentation of Patient

Medical Nutrition Therapy

Medical Treatment

Epilepsy Anatomy & Physiology

The Brain

Anatomy & Physiology

Neuron Synapse

Anatomy & Physiology

Seizure

Anatomy & Physiology

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 Absence Clonic Myoclonic Tonic Atonic

Definition

History

Etiology

Diagnosis

Medical Treatment

Non-Surgical

Surgical

Epilepsy

Definition

2+ unprovoked seizures occurring 24+ hours apart

Diagnosis of an epilepsy syndrome

Resolved if: Past applicable age of

age-dependent syndrome

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

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

Epilepsy

Migraine

Stroke

Alzheimers

2.2 million

What did

Alexander the Great, Julius Caesar, Joan of Arc, Hndel,

Flaubert, van Gogh, and Gershwin

have in common?

POP QUIZ

History

History

1516-1520, Italy The Transfiguration by Raphael

History

Stigma

Misconception

Unpredictable

Helplessness

Etiology

Genetic

Structural/Metabolic

Unknown

Diagnosis

Clinic Visit

Medical History

Seizure History

Neurological Exam

Laboratory Results

Imaging (EEG, MRI, CT)

Diagnosis

Medical Intervention

Dietary Treatment

Surgical Resection Disconnection Stimulation

Seizure Medications

First developed 150 years ago

NON-SURGICAL Seizure Medications

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

NON-SURGICAL Seizure Medications

Carbamazepine

Clobazam

Clonazepam

Diazepam

Divalproex Sodium

Felbamate

Gabapentin

Lamotrigine

Levitracetam

Lorazepam

Phenobarbital

Phenytoin

Pregbalin

Rufinamide

Topiramate

Valproic Acid

Vigabatrin

Zonisamide

First line of treatment

Mechanism: neurotransmitters

Side effects: weight, appetite, dizziness, depression, sedation

Careful choice by MD

% Seizure Control

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

SURGICAL

Stimulation

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

Vagus Nerve Stimulator

Fasting

Metabolic Changes During Starvation

NON-SURGICAL Dietary Treatment

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

Fasting

Ketogenesis Pathway

NON-SURGICAL Dietary Treatment

Fasting

Metabolic Changes During Starvation

NON-SURGICAL Dietary Treatment

Fasting

Metabolic Changes During Starvation

NON-SURGICAL Dietary Treatment

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

0%

20%

40%

60%

80%

100%

Typical Ketogenic

30

90 15

7

55

3

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

Assessment

Estimations

WHO Equation, REE x Activity Factor

Age Males Females

0-3 60.9W 54 61.0W 51

3-10 22.7W + 495 22.5W + 499

10-18 17.5W + 651 12.2W + 746

18-30 15.3W + 679 14.7W + 496

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

1.7 Active requiring catch-up growth Active with severe stress

RDA

Age Kcal/kg gm protein/kg

0-6 months 108 1.52 (AI)

7-12 months 98 1.2

1-3 years 102 1.05

4-6 years 90 0.95

7-10 years 70 0.95

11-14 years 55 0.85 (14-18)

15-18 years 45 0.85

11-14 years 47 0.85 (14-18)

15-18 years 40 0.85

Fluid Requirements

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

FAQs

Do kids get fat?

High cholesterol?

How strict?

Life long?

Meet

SP

Presentation of Patient

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

3-day diet record

Creamy, fatty foods

No rice, pasta

Chocolate milk

Needs

REE = 1838 kcal

AF: 1.2-1.4

2205-2573 kcals per

day

Protein: 0.85

g/kg/day

Fluid: 1842-2456 mL/day

SP Assessment

Labs Medications

Klonopin

Depakote

Topamax

Diastat

Tranxene

Glucose mg/dL 90

Cholesterol mg/dL 131

Triglyceride mg/dL 114

HDL Cholesterol

mg/dL

32 (L)

LDL-Cholesterol

mg/dL

76

Betahydroxybutyrate

mmol/L

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 nutrition-

related 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

Classes

Weighing Food

Exchanges

Keto Kitchen

Cooking Demos

U Arts Interns

SP Monitoring & Evaluation

Hospital Course

Tolerated advance

No N/V

Complaints of hunger resolved

Music therapy &

video games

Progression of ketosis

Ref.

Range

Dec 9

21:40

Dec 10

01:30

Dec 10

09:00

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

Glucose 70-106

mg/d

92 105 80 82 86 91 68 (L) 82 94 87

BHB 0.0-0.3

mmol/L

0.38 (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

M E R Y L

Summary

Looking Ahead

Other applications

Asia

Hindmilk?

Keto pill?

Comments

Dr. Christina Bergqvist

Separation from child

Mobile app

KD room

service

Cagla Fenton, RD, LDN

Sue Groveman, MS, RD, LDN

Donna DiVito, RD, LDN, CNSC

Avi Weiner, DMD

Mollie & Ron Makar

Acknowledgements

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.1528-

1167.2008.01821.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?