الفهرس 
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Abstract
Epilepsy is a common chronic neurological disorder characterized by recurrent, unprovoked seizures; these seizures are transient signs of abnormal excessive or synchronous neuronal activity in the brain.
About 50 million people worldwide have epilepsy with almost 90% of these people being in developing countries. The annual incidence of epilepsy per 100. 000 population is 86 in the first year of life, 62 at age 1-5 years, 50 at age 5-9 years, and 39 at age 10-14 years.
According to pathophysiology of epilepsy, two sets of changes can determine the epileptogenic properties of neuronal tissue; abnormal neuronal excitability is believed to occur as a result of disruption of depolarization and repolarization mechanisms (excitability of neuronal tissue), aberrant neuronal networks that develop abnormal synchronization of a group of neurons can result in the development and propagation of an epileptic seizure (synchronization of neuronal tissue).
Nowadays, different mutations in genes that control the excitability of neurons have been described in childhood epilepsy.
Epilepsy has a wide range of causes, and indeed almost all grey matter diseases can result in seizures and the most important factor influencing the range of causes is age.
The diagnosis of epilepsy remain very much a clinical skill, specially in children, causes of wrong diagnosis include, inadequate history taking, failure to recognize a differential diagnosis, undue reliance on an EEG. Accurate diagnosis leads directly to proper treatment and formulation of rational plan of management.
Therapy of epilepsy has three goals: the first, to eliminate seizures or reduce their frequency to the maximum extent possible, the second, to avoid the side Effects associated with long term treatment, the third, to assist the patient in maintaining normal activities.
In those patients who become seizure free with medications, withdrawal of the AED can be considered after a seizure free interval has been maintained for 2 years, the withdrawal should be done gradually such as by decreasing the daily dose by 25% every 2 or 4 weeks.
Seizures are well controlled with a single anticonvulsant in most patients with epilepsy. However approximately 20% of patients with primary generalized epilepsy and 35% of patient with focal epilepsy have medically intractable seizures.
Medically refractory epilepsy defined as inadequate seizure control despite appropriate medical therapy with at least 2 AEDS in maximally tolerated doses for 18 months-2 years, or adequate seizure control with unacceptable drug related side effects.
There are several factors to be considered in a definition of medical intractability, including: the number of AED failure, minimum frequency at which seizure must occur to be considered intractable, duration of unresponsiveness to medication, epilepsy syndromes involved, causes of seizures in the absence of clear cut epilepsy syndrome, and patient age at the onset of seizures.
The transporter and target hypotheses are the most commonly cited mechanisms of refractoriness.
For diagnosis of intractable epilepsy we should respond to the following questions:
a) Does the patient have epilepsy? b) What is the underlying cause? c) Is the epilepsy truly intractable?
Management of epilepsy includes various modalities:
Surgical treatment: children with intractable epilepsy may benefit from early surgical intervention to avoid the potential negative effects of continued seizures and prolonged use of AEDs on cognitive and psychosocial development and to increase the chances of postoperative neurological reorganization due to inherent functional plasticity of a child’s brain.
For patients who are not good candidates for epilepsy surgery other modalities are available as ketogenic diet which based on clinical experience that any diet produce sustained ketonemia and lowers blood sugar has an anticonvulsant effect. It takes about 3-6 months for the efficacy for the diet to be established, but once that happens, AEDs may be tapered overall. Thirty to fifty percent of children respond favourably, those who respond show dramatic improvement with at least a 50% reduction in seizure frequency within 2-3 weeks, the ketogenic diet is often unpalatable for an awake and alert patient, but an alternative modified Atkins diet can induce ketosis in a more acceptable form.
VNS may be an effective alternative treatment for patients with intractable epilepsy who are not candidates for epilepsy surgery. The proposed mechanisms of how VNS modulate seizure control include alteration of norepinephrine release by projection of solitary tract to the locus cerulean, elevated level of inhibitory GABA related to vagal stimulation and inhibition of aberrant cortical activity by reticular system activation. It was cited that VNS reduce seizure rates in children by 20-30% within 3 months of insertion, and by 40-50% after 18-24 months of treatment.
Radiosurgery now is being evaluated as an alternative treatment to open resective surgery for intractable epilepsy. Radiosurgery is being applied as different modalities including LINAC, Gamma Knife, and Proton beam stereoactic radiosurgery.
Also ACTH and Corticosteroids are used successfully in the treatment of intractable epilepsy. It was demonstrated that high dose ACTH therapy was superior to prednisone their mechanisms in treatment of intractable epilepsy include correction of deficient or dysfunctional enzymes, changes in intracellular-extracellular electrolyte ratios, correction of hypoglycemia, reduction in cerebral water content, anti inflammatory action, and immune modulation or suppression.
The use of Ig in the treatment of refractory epilepsy presented satisfactory responses; according to some authors, had given that reduction in number of seizures varied from 30%-80%. The side effects include fever, allergic reaction, and the risk of blood borne infections. It is a very expensive option particularly if treatment is maintained with repeated courses.
Children with refractory epilepsy are at considerable risk for cognitive impairment, school failure, behavior and mental health problem.