The ketogenic diet in pharmacoresistant childhood epilepsy

Abstract

Available pharmacologic treatments for seizures are limited in their efficacy. For a patient with seizures, pharmacologic treatment with available anticonvulsant medications leads to seizure control in <70% of patients. Surgical resection can lead to control in a select subset of patients but still leaves a significant number of patients with uncontrolled seizures. The ketogenic diet and related diets have proven to be useful in pharmacoresistant childhood epilepsy.

Keywords:

• doose syndrome
• epilepsy
• GLUT-1 deficiency
• infantile spasms
• ketogenic
• lennox-gastaut syndrome
• low glycemic index diet
• MCT diet
• modified atkins diet
• seizures

Financial & competing interests disclosure

EH Kossoff has served as a consultant for Atkins Nutritionals, Eisai, Upsher-Smith, NeuroPace and Nutricia. He has also served on the data safety monitoring board for Lundbeck and has received royalties from Demos and UpToDate. SK Bessone serves as consultant for Nutricia on ketogenic diet. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• The ketogenic diet is a high-fat, adequate protein, low carbohydrate diet used for epilepsy utilizing strictly controlled amounts and ratios of fat to a combination of protein and carbohydrates.

• The ketogenic diet has been shown to decrease seizures by 50% in 56% of pharmacoresistant patients with epilepsy in a wide variety of epilepsy syndromes. In addition, 10–15% of patients become seizure free on the diet.

• The mechanism of action for the ketogenic diet remains elusive at the present time. Theories include possible anticonvulsant effects of ketone bodies generated by the diet, modulation by the ketone bodies on glutamergic and gabaergic neurotransmitter metabolism, modulation of biogenic amines and the effect on mitochondria by the change in metabolism to a fatty acid based rather than glucogenic metabolism.

• The ketogenic diet is the treatment of choice for patients with glucose transporter 1 (GLUT-1) deficiency where ketone bodies generated by the diet replace the diminished glucose in the brain as an energy substrate.

• In clinical studies, patients with Doose syndrome (myoclonic astatic epilepsy), an often pharmacoresistant syndrome, have responded well to the ketogenic diet, supporting early consideration of the ketogenic diet in these patients.

• The ketogenic diet has been shown to be helpful among patients with epileptic encephalopathies, including Lennox–Gastaut syndrome, Dravet syndrome and Rett syndrome.

• The ketogenic diet is a viable option for infantile spasms if readily available. Patients can be tried for 2 weeks and if unresponsive, can then be converted to pharmacologic therapy.

• The ketogenic diet should be considered early for treatment of pharmacoresistant epilepsy in children fed with enteral tubes. The availability of commercially available formulas simplifies institution of the ketogenic diet.

• The modified Atkins diet is a low-carbohydrate diet with a prescribed limit of carbohydrate and unlimited protein and fat. It is a simplified, less restrictive ‘ketogenic’ diet that has been shown to be helpful in pharmacoresistant patients with epilepsy. It can be instituted with less dietician resources and may be especially useful in adolescent and adult populations as well as resource-poor areas.

• The LGIT is a viable treatment that includes a more liberal carbohydrate intake. It uses estimated portions and household measurements to monitor food intake. It has been proven to have similar efficacy to the classical ketogenic diet which may bring opportunities for patients to have success with less restrictive guidelines.

• The ketogenic diet should be weaned after 2 years in most patients with epilepsy. This avoids long-term side effects, particularly, on growth and studies have shown that many may continue to do well after weaning of the diet. Notable exceptions are patients with GLUT-1 deficiency and possibly Dravet syndrome. Those that relapse may be restarted on the diet.