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Ketogenic diet: twenty years of experience

Pierangelo Veggiotti

Pavia 27 aprile 2015

Ketogenic Diet

Normocaloric diet with high intake of lipids and low intake of carbohydrates and proteins, that resembles a prolonged fasting

“Ketogenic” = means the depletion of a whole class of nutrients, carbohydrates; this condition promotes the synthesis of ketones as energetic substrate for the CNS, instead of glucose

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� LCT Long Chain Triglycerides 4:1 / 3:1

� MCT Medium Chain Triglycerides

� MCT Modified by John Radcliff Infirmary

� MAD Atkins Diet

� LGIT Low Glycemic Index Treatment

� Liquid formulated products KetoCal ®(Nutricia, SHS)

KD types

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EPILEPSY

DIAGNOSIS

TWO MEDICAL

TREATMENTS

NO SURGICAL INDICATION

DRUG RESISTANTEPILEPSY

ALTERNATIVETHERAPIES

KETOGENIC DIET

ACTH OR

CORTICOSTEROIDES

OTHER MEDICALTREATMENTS

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From 1994 to 2014

23 patients with GLUT1 deficiency

At about 80 patients with refractory epilepsy

DIET TYPE: classical KD - ketogenic ratio 4:1/ 3:1/ 2:1

Actual database with 60 patients follow-up

Our experience

From 11 months to 303 months

� Median age 105.5 months

Age starting the diet

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From 11 months to 230 months

Median of the history of disease: 70 months

History of disease when startingthe diet:

Electroclinical diagnosis

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Follow up duration: from 3 months to 138 months

Mean KD duration:

Patients undergoing KD for more than 12 months:

27

Patients undergoing KD for more than 24 months:

13

KD duration- groups of patients

Electroclinical diagnosis:

Epileptic Enkephalopathy

Etiological diagnosis:

Metabolic disorder

Patients who continued the diet forlongest periods

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02468

101214161820

No seizure >50%reduction

<50%reduction

Seizures frequency at 1 month23 patients showed no frequency changes

37 patients showed frequency reduction

Seizures Frequency at 3 months

31 patients showed no change compared to t029 patients showed frequency reduction compared to t0

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No one of the group completely seizure free at 1 month mantained such a result at 3 months and after.

The group of patients seizure free after 3 months underwent a gradual reduction of seizure frequency

Efficacy trend

Cortical malformations

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Awake Sleep

Baseline

6 months

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-Inefficacy. But after which interval of time can we saythat the diet is not effective?

-Compliance. Either children refusal of food restriction or parents’ choice

-Side effects

Moreover, often Upper Respiratory tract infection(common in the many compromised pts, may precipitate the control of seizure obtained thanks to a positive response to KD)

Suspension causes:

-Constipation and altered bowel habits

-Weight loss/ weight gain

-Kidney stones

-Liver steatosis

-Altered liver function

In our set of patients

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� Reactivity: qualitative changes assessment

( is there a progressive improvement? When is a plateau reached. From the very beginning?)

Important as well as a reduction in frequency?

Should the diet be continued if only reactivity is improved?

->Ad hoc, perspective study sheet to fill, for better assessment and insights

Insights for better efficacy evaluation

� Reactivity assessment. Important parameter, 75%of patients show reactivity improvement

How to evaluate it? To be considered:

o Daily attention - ketosiso Partecipation, eye contacto Motor improvement, deambulationo Lallation, language

Insights for better efficacy evaluation

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-Potassium citrate supplement to prevent nephrolithiasis

-General tendency to drink less: to be prevented

-Initiation with/ without fasting

-Contraindications

-Compliance; more products and formulas available

-Pre-Diet assessment and screening in order to be able to attribute potential side effects at the diet: family history of nephrolitiasis, renal and liver ecography, liver function exc.

By better experiencing the Diet…

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PDH Deficiency Syndrome

Many mutations : AR, sporadic, X-linked ( E1α)

Impairment of Pyruvate Dehydrogenase Complex (PD)

CNS malformations

Fatal Neonatal lactic Acidosis

Alpers syndrome

Leigh syndrome

Carbohydrates responsive ataxia

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Conclusions

Open questions:

� How does the KD work?

� Which type of KD is more effective with a good tolerability?

� Is hospitalisation useful ?

� Which variables (diagnosis, type of seizure, age start delay…)can we use to predict the response to the KD?

Conclusions

� Start earlier

� Identifying genes and biomarkers in candidates for KD

� Improve dietician knowledge

� Increase series

� Overcome the prejudice

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Grazie a tutti quelli che mi sopportano/supportano ogni giorno