Local distribution and toxicity of prolonged hippocampal
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imately 15,000 to 30,000 people each year in the US. Epilepsy is considered intractable when it significantly reduces the quality of a person’s life, either because frequent seizures persist despite appropriate doses and types of antiepilepsy medications or because the control of seizures is possible only with medication dosages that produce excessive sedation.34 In most cases of surgically remediable medically intractable epilepsy, the pathological disorder is mesial temporal sclerosis, a condition in which the seizure focus is located in one of the hippocampi. Standard treatment for this condition requires frontotemporal craniotomy for removal of the affected hippocampus. Such surgery is successful in eliminating seizures in two of three patients, in preventing cerebral degeneration and death from repeated seizures, and in avoiding the detrimental effects of toxic doses of medication on learning and job performance.45 In most patients with epilepsy, oral medication provides seizure control because it produces drug levels in the brain that are sufficient to suppress the epileptic focus but insufficient to suppress cognitive activity. For patients with medically intractable epilepsy, however, moderate drug levels are incapable of suppressing the epileptic focus; efforts to further increase the drug dose generate levels that suppress neural activity throughout the brain and cause cognitive side effects. Medication delivered by mouth or vein results in drug levels in the epileptic focus that are approximately equal to those in the rest of the brain; because medication is not specifically targeted to the epileptic focus, improved seizure control comes with the cost of increased cognitive side effects. The link between improved control of seizures and cognitive side effects could be broken if a method were developed to preferentially deliver drugs directly to the seizure focus. Because the seizure focus in many patients with medically intractable epilepsy is located in the hippocampus, selective suppression of neuronal activity in this discrete anatomical structure could potentially control this type of epilepsy and avoid cognitive side effects. Although the
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تاریخ انتشار 2005