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Topic Outline
INTRODUCTION
Antiepileptic drugs (AEDs) are the primary treatment for epileptic seizures, and are effective in controlling seizures in most patients. However, approximately one-third of patients will not become seizure-free with medications and require nonpharmacologic treatments [1]. Although epilepsy surgery is usually considered for these patients, there are many families and patients who are either unwilling to consider or are not candidates for epilepsy surgery, either because surgery would lead to intolerable motor, language, or memory deficits or for other reasons. In these patients, treatments such as vagus nerve stimulation (VNS) and diets are then considered.
This topic will review the ketogenic diet and alternative diets for the treatment of epilepsy. Some of the preliminary evidence for use of the ketogenic diet in other neurologic conditions will also be briefly reviewed. Other treatments for seizures and epilepsy in adults and children with epilepsy are reviewed separately. (See "Overview of the management of epilepsy in adults" and "Overview of the treatment of seizures and epileptic syndromes in children" and "Vagus nerve stimulation therapy for the treatment of epilepsy" and "Initial treatment of epilepsy in adults" and "Surgical therapy of epilepsy in adults".)
MECHANISMS OF ACTION
Published reports of the ketogenic diet as an effective treatment for epilepsy date to the early 1920s [2]. However, the mechanism(s) by which the ketogenic diet suppresses seizures remains unclear and is likely multifactorial [3].
The ketogenic diet utilizes a high fat, adequate-protein (1 gram/kg), low-carbohydrate diet that produces metabolic changes often associated with the starvation state. Often started with a brief fasting period, changes in plasma ketones, insulin, glucose, glucagon, and free fatty acids can occur within hours of starting the diet and can be quite profound [3].
Which of these metabolic changes are responsible for the improvement in seizure frequency is not known. The ketogenic diet was so called based upon the theory that ketone bodies (acetoacetate, acetone, and beta-hydroxybutyrate), created in the liver from long and medium-chain fatty acids, are directly anticonvulsant when crossing the blood-brain barrier. Urine and occasionally serum ketone levels are generally checked in patients on the ketogenic diet to ensure the diet is being managed correctly, in a manner analogous to following antiepileptic drug levels [4].
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