The ketogenic diet in children, adolescents and young adults with refractory epilepsy: an Italian multicentric experience

Coppola, Giangennaro; Veggiotti, Pierangelo; Cusmai, Raffaella; Bertoli, Simona; Cardinali, Simonetta; Dionisi‐Vici, Carlo; Elia, Mirella; Lispi, Maria Luisa; Sarnelli, Chiara; Tagliabue, Anna; Toraldo, Caterina; Pascotto, Antonio

doi:10.1016/s0920-1211(01)00315-1

Cited by 143 publications

(109 citation statements)

References 15 publications

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“…Tail vein whole blood β-HB was measured every other day using test strips and a hand-held device (Precision Xtra, Abbott Laboratories, Alameda, CA, USA). At the end of the 7-day feeding period, the CT and KD groups were each separated into two subgroups for the substrate infusion: [1][2][3][4][5][6][7][8][9][10][11][12][13] C]Glc or [2,[4][5][6][7][8][9][10][11][12][13] C 2 ]β-HB (n = 6/subgroup). The experimental protocol was approved by the Institutional Animal Research Ethics Review Board and met the guidelines of the French governmental agency (In accordance with ARRIVE: personal authorization no.…”

Section: Introductionmentioning

confidence: 99%

Rapid Adaptation of Rat Brain and Liver Metabolism to a Ketogenic Diet: An Integrated Study Using ¹H- and ¹³C-NMR Spectroscopy

Roy

Beauvieux

Naulin

et al. 2015

J Cereb Blood Flow Metab

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The ketogenic diet (KD) is an effective alternative treatment for refractory epilepsy in children, but the mechanisms by which it reduces seizures are poorly understood. To investigate how the KD modifies brain metabolism, we infused control (CT) and 7-day KD rats with either [1-13 C]glucose (Glc) or [2,4-13 C 2 ]β-hydroxybutyrate (β-HB). Specific enrichments of amino acids (AAs) measured by 1 H-and 13 C-NMR in total brain perchloric acid extracts were similar between CT and KD rats after [1-13 C]Glc infusion whereas they were higher in KD rats after [2,4-13 C 2 ]β-HB infusion. This suggests better metabolic efficiency of ketone body utilization on the KD. The relative rapid metabolic adaptation to the KD included (1) 11%-higher brain γ-amino butyric acid (GABA)/glutamate (Glu) ratio versus CT, (2) liver accumulation of the ketogenic branched-chain AAs (BCAAs) leucine (Leu) and isoleucine (ILeu), which were never detected in CT, and (3) higher brain Leu and ILeu contents. Since Glu and GABA are excitatory and inhibitory neurotransmitters, respectively, higher brain GABA/Glu ratio could contribute to the mechanism by which the KD reduces seizures in epilepsy. Increased BCAA on the KD may also contribute to better seizure control.

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Section: Introductionmentioning

confidence: 99%

Rapid Adaptation of Rat Brain and Liver Metabolism to a Ketogenic Diet: An Integrated Study Using ¹H- and ¹³C-NMR Spectroscopy

Roy

Beauvieux

Naulin

et al. 2015

J Cereb Blood Flow Metab

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“…Although they tolerated the ketogenic diet poorly, these five patients were responders at 1 week, including two who became seizure-free, with seizure control maintained at 1 month (3,9). The three others relapsed one week after stopping the diet.…”

Section: Results (mentioning

confidence: 95%

“…The ketogenic diet was stopped during the first month in seven patients: in two (10, 15) because of inefficacy after 10 days and 3 weeks respectively, and in the five others (3,8,9,20,21) because of adverse events (severe vomiting and fatigue). Although they tolerated the ketogenic diet poorly, these five patients were responders at 1 week, including two who became seizure-free, with seizure control maintained at 1 month (3,9).…”

Section: Results (mentioning

confidence: 99%

“…1,2 Many investigators have confirmed the benefits that this treatment can offer to young patients with epilepsy, [3][4][5][6] including infants. 7,8 However, the best indications for using the diet have not been clearly defined since it was shown to be helpful in treating a large range of different seizure types and epilepsy syndromes.…”

mentioning

confidence: 94%

“…16 Lack of complex focal seizures was reported as a predictive factor for early, complete, and sustained response. 3 However, studies that addressed the effects of the ketogenic diet according to the type of seizures or epilepsy failed to identify any significant difference. 17,18 Animal studies have concentrated more on models for generalized convulsions 19,20 than on focal seizures, 21 although in both instances ketosis proved to be efficient.…”

mentioning

confidence: 99%

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The ketogenic diet improves recently worsened focal epilepsy

Villeneuve

Pinton

Bahi‐Buisson

et al. 2009

Develop Med Child Neuro

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Aim We observed a dramatic response to the ketogenic diet in several patients with highly refractory epilepsy whose seizure frequency had recently worsened. This study aimed to identify whether this characteristic was a useful indication for the ketogenic diet. Method From the 70 patients who received the ketogenic diet during a 3‐year period at our institution, we retrospectively selected patients with focal epilepsy. There were 22 children, 13 females and nine males, aged from 5 months to 18 years 6 months (mean 6y 9mo, SD 5y 11mo). Fifteen had symptomatic and seven had cryptogenic focal epilepsy. Seizure frequency 1 week before initiating the ketogenic diet was compared with that at 1 month and at the last visit on the diet. Results Eleven patients were responders (defined as reduction of seizures by more than 50%) at 1 month. Responders were higher (p=0.046) in the group with a recent worsening of seizures than in those with stable seizure frequency. Seven patients were still seizure‐free at 6 months on the diet. Tolerability was excellent in 10 patients. Five patients stopped the diet because of early side effects. Interpretation The ketogenic diet may be a valuable therapeutic option for children with pharmacoresistant focal epilepsy, particularly those with a recent deterioration of seizure control and neurological status. Because of its rapid effect, the ketogenic diet may be a useful support to intravenous emergency drugs in such a situation.

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Ketogenic diet and other dietary treatments for epilepsy

Levy

Cooper

Giri

et al. 2012

Cochrane Database of Systematic Reviews

206

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The ketogenic diet in children, adolescents and young adults with refractory epilepsy: an Italian multicentric experience

Cited by 143 publications

References 15 publications

Rapid Adaptation of Rat Brain and Liver Metabolism to a Ketogenic Diet: An Integrated Study Using ¹H- and ¹³C-NMR Spectroscopy

Rapid Adaptation of Rat Brain and Liver Metabolism to a Ketogenic Diet: An Integrated Study Using ¹H- and ¹³C-NMR Spectroscopy

The ketogenic diet improves recently worsened focal epilepsy

Ketogenic diet and other dietary treatments for epilepsy

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The ketogenic diet in children, adolescents and young adults with refractory epilepsy: an Italian multicentric experience

Cited by 143 publications

References 15 publications

Rapid Adaptation of Rat Brain and Liver Metabolism to a Ketogenic Diet: An Integrated Study Using 1H- and 13C-NMR Spectroscopy

Rapid Adaptation of Rat Brain and Liver Metabolism to a Ketogenic Diet: An Integrated Study Using 1H- and 13C-NMR Spectroscopy

The ketogenic diet improves recently worsened focal epilepsy

Ketogenic diet and other dietary treatments for epilepsy

Contact Info

Product

Resources

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Rapid Adaptation of Rat Brain and Liver Metabolism to a Ketogenic Diet: An Integrated Study Using ¹H- and ¹³C-NMR Spectroscopy

Rapid Adaptation of Rat Brain and Liver Metabolism to a Ketogenic Diet: An Integrated Study Using ¹H- and ¹³C-NMR Spectroscopy