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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