A Cochrane systematic review in 2018 found and analysed eleven randomized controlled trials of ketogenic diet in people with epilepsy for whom drugs failed to control their seizures. Six of the trials compared a group assigned to a ketogenic diet with a group not assigned to one. The other trials compared types of diets or ways of introducing them to make them more tolerable. In the largest trial of the ketogenic diet with a non-diet control, nearly 38% of the children and young people had half or fewer seizures with the diet compared 6% with the group not assigned to the diet. Two large trials of the Modified Atkins Diet compared to a non-diet control had similar results, with over 50% of children having half or fewer seizures with the diet compared to around 10% in the control group.
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The ketogenic diet reduces seizure frequency by more than 50% in half of the patients who try it and by more than 90% in a third of patients. Three-quarters of children who respond do so within two weeks, though experts recommend a trial of at least three months before assuming it has been ineffective. Children with refractory epilepsy are more likely to benefit from the ketogenic diet than from trying another anticonvulsant drug. Some evidence indicates that adolescents and adults may also benefit from the diet.
The low glycemic index treatment (LGIT) is an attempt to achieve the stable blood glucose levels seen in children on the classic ketogenic diet while using a much less restrictive regimen. The hypothesis is that stable blood glucose may be one of the mechanisms of action involved in the ketogenic diet, which occurs because the absorption of the limited carbohydrates is slowed by the high fat content. Although it is also a high-fat diet (with approximately 60% calories from fat), the LGIT allows more carbohydrate than either the classic ketogenic diet or the modified Atkins diet, approximately 40–60 g per day. However, the types of carbohydrates consumed are restricted to those that have a glycaemic index lower than 50. Like the modified Atkins diet, the LGIT is initiated and maintained at outpatient clinics and does not require precise weighing of food or intensive dietitian support. Both are offered at most centres that run ketogenic diet programmes, and in some centres they are often the primary dietary therapy for adolescents.
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In the mid-1990s, Hollywood producer Jim Abrahams, whose son's severe epilepsy was effectively controlled by the diet, created the Charlie Foundation to promote it. Publicity included an appearance on NBC's Dateline programme and ...First Do No Harm (1997), a made-for-television film starring Meryl Streep. The foundation sponsored a multicentre research study, the results of which—announced in 1996—marked the beginning of renewed scientific interest in the diet.
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The nerve impulse is characterised by a great influx of sodium ions through channels in the neuron's cell membrane followed by an efflux of potassium ions through other channels. The neuron is unable to fire again for a short time (known as the refractory period), which is mediated by another potassium channel. The flow through these ion channels is governed by a "gate" which is opened by either a voltage change or a chemical messenger known as a ligand (such as a neurotransmitter). These channels are another target for anticonvulsant drugs.
There are many ways in which epilepsy occurs. Examples of pathological physiology include: unusual excitatory connections within the neuronal network of the brain; abnormal neuron structure leading to altered current flow; decreased inhibitory neurotransmitter synthesis; ineffective receptors for inhibitory neurotransmitters; insufficient breakdown of excitatory neurotransmitters leading to excess; immature synapse development; and impaired function of ionic channels.