الفهرس 
The use of ketogenic diet in epilepsyOnly 14 pages are availabe for public view
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Abstract
D
rug resistant epilepsy is an everyday challenge facing neurologists owing about one third of patients with epilepsy. Those who did not achieve complete seizure control for 12 consecutive months with the first two or three Anti-epileptic drugs were given the predictive diagnosis of refractory or drug-resistant epilepsy, 20 % of those with generalized epilepsy and around 35% of those with partial epilepsy.
Since about one third of epilepsy is refractory to pharmacological treatment new modalities of treatment have emerged in recent years, many of these being non-pharmacological as epilepsy surgeries, deep brain stimulation (DBS), transmagnetic stimulation (TMS), vagal nerve stimulation and life style modification such as ketogenic diet and sleep therapy as well as gene and cell therapy which are still under trials.
The ketogenic diet could be considered the first treatment for epilepsy ever used with historical background since patients were put into strict fasting, ketogenic diet is achieved by too low a proportion of carbohydrate and too high a proportion of fat which inturn resembles fasting. The mechanism of action is not very well understood yet the efficacy of this treatment is very well established and studied with 30 to70 percent of patients having more than 50 % response and up to 10- 20 % seizure free putting into consideration that these patients are pharmaco resisitant this makes Ketogenic diet relatively very effective. It is best tried in young children. Myoclonic or ‘DROP’ seizures, as well as atypical absence seizures, did seem to respond particularly well the International Consensus Statement for the Ketogenic Diet (2009) stated that “the [ketogenic diet] should be considered in a childwho has failed two to three anticonvulsant therapies, regardless of age or gender, and particularly in those with symptomatic generalized epilepsies.”. Specifically, the ketogenic diet appears to be a particularly effective treatment for persons with Dravet and Doose syndromes, and becoming a therapy of choice refractory infantile spasms. Early-onset adverse effects associated with diet initiation include acidosis, hypoglycemia, gastrointestinal distress, dehydration, and lethargy, Later adverse effects include dyslipidemia, kidney stones, and slowing of growth.
Surgical treatments for epilepsy include a variety of operations, almost all of which aim to eliminate seizures without producing a new neurological deficit. These operations are collectively termed epilepsy surgery. Other surgical interventions include operations that are palliative by either producing a disconnection within the brain or the placement of an electronic nerve stimulator. Curative procedures include lobectomy, lesionectomy, and hemispherectomy. Palliative procedures include corpus callosotomy, multiple subpial transections and vagus nerve stimulation and deep brain stimulation.
The impact of epilepsy surgery in adults, mostly with drug-resistant temporal lobe epilepsy, can be summarized tentatively as follows: Following surgery, approximately one-third of adult patients is cured (seizure-free without medical treatment), one-third is controlled with continued medical treatment, and one-third will continue to have recurrent disabling seizures.
Resective epilepsy surgery may not be a good option for every patient with intractable epilepsy because the outcome may be less favorable when onset is extra-temporal or more diffuse and so patients with partial-onset seizures not achieving control with three or more AEDs (in mono- or combination therapy) may be offered VNS as a viable option for treatment of their epilepsy with an efficacy of around third of patients experiencing a 50% reduction in seizure frequency with mild usually tolerated side effects including hoarseness, cough, and dysphagia are intensity dependent, which diminish over time, and are usually not limiting. VNS initially stimulates deep brain regions (the vagus through the NTS and locus), with secondary stimulation of limbic cortex. This might be labeled a ‘bottom-up’ approach to brain stimulation.
In contrast, TMS is limited to direct superficial cortical stimulation, with secondary effects on subcortical structures (a ‘top-down’ approach). In normal subjects, application of low-frequency trains of rTMS produces a relatively long-lasting suppression of cortical excitability and this phenomenon has been implicated for the use of low frequency rTMS in treatment of epilepsy with good results yet the effect lasts only for about 2 month.
In recent years deep brain stimulation has become established as an effective treatment for movement disorders that is usually also safe over the long term and is now being used to treat epilepsy, a variety of sites are approached and they include cerebellum, caudate nucleus, thalamic, centromedian nucleus, anterior thalamic nucleus, subthalamic nucleus, and epileptic focus with an efficacy reaching up to 50 percent reduction in half of patients .side effects include those of the stereotactic surgery as infection or bleeding or those of stimulation as facial muscle twitches and sometimes behavioral changes.
A number of naturally occurring brain substances, such as GABA, adenosine, noradrenaline, acetylcholine and the neuropeptides galanin and neuropeptide Y, may function as endogenous anticonvulsants and, in addition, may interact with the process of epileptogenesis., In recent years a new field of cell and gene-based neuropharmacology has emerged, aimed at either delivering endogenous anticonvulsant compounds by focal intracerebral transplantation of bioengineered cells (ex vivo gene therapy), or by inducing epileptogenic brain areas to produce these compounds in situ (in vivo gene therapy).
Cell transplant has also been studied for structural repair of damaged epileptic networks: by Foetal hippocampal cell transplantation and Neural stem/progenitor cell transplantation. These are still under investigation with promising results in very few man trials with many studies as regards safety and ethical issues are yet to be resolved.
One noninvasive procedure that has been recently studied for its effect on epilepsy is the use of CPAP for obstructive sleep apnea in patients with epilepsy and it showed significant results and improvement as regards control of seizures. Another noninvasive tool that has been in clinical trials over the past few years is the use of neurofeedback in the control of refractory epilepsy.
At last the use of ECT in control of epilespsy has shown relatively good results in the treatment of refractory status epileticus and non convulsive status epileticus yet the studies on its effect are rare and depend mainly on case studies.
Finally it could be concluded that a patient with medically refractory epilepsy would be very much suffering as well as his family and predicting his refractoriness early by the treating doctor would spare much time in this suffering. Many options of nonpharmacological treatment could be offered for this patient either with focal or generalized epilepsy and the sooner the better especially if the patient is surely diagnosed.