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Patients in this study will undergo PET scans (a type of nuclear imaging test) to look for abnormalities in certain brain proteins associated with seizures.
Studies in animals have shown that serotonin-a chemical messenger produced by the body-attaches to proteins on brain cells called 5HT1A receptors and changes them in some way that may help control seizures. There is little information on these changes, however. A new compound that is highly sensitive to 5HT1A, will be used in PET imaging to measure the level of activity of these receptors and try to detect abnormalities. Changes in receptor activity may help determine where in the brain the seizures are originating.
Additional PET scans will be done to measure the amount of blood flow to the brain and the rate at which the brain uses glucose-a sugar that is the brain's main fuel. Blood flow measurement is used to calculate the distribution of serotonin receptors, and glucose use helps determine how seizures affect brain function.
The information gained from the study will be used to try to help guide the patient's therapy and determine if surgery might be beneficial in controlling the patient's seizures.
Objective: to study serotonin receptors in patients with localization-related epilepsy. Studies in experimental animals have suggested that: Serotonin is an anticonvulsant neurotransmitter in a number of seizure models; its anticonvulsant action is mediated by activation of 5-HT(1A) receptors; drugs with antiepileptic effects may release 5HT or block reuptake, and these mechanisms appear to be related to their therapeutic effect. 5HT(1A) receptors are abundant in regions such as entorhinal cortex, hippocampus, and temporal neocortex, where epileptogenic zones are frequently found. Considerable evidence from literature indicates that alterations in 5-HT(1A) receptors exist in experimental models of both generalized and complex partial seizures. There is little data on changes in 5-HT receptors in epileptic patients.
Study population: 75 patients with localization-related epilepsy and 20 normal controls, aged 18-60.
Design: Using a new PET compound which is a highly selective 5-HT(1A) silent antagonist referred to as (18)FCWAY, we will attempt to detect abnormalities in serotonin receptors in vivo in patients with epilepsy. The patients will have (18)FCWAY serotonin receptor studies (which include (15)H2O-CBF PET) and high resolution T1-weighted MRI for co-registration. (18)FDG-PET will be performed in the patients as part of seizure focus localization. We will also test subjects for the serotonin transporter polymorphism associated with depression, and perform a standard depression battery.
Outcome measures: 5HT-1A receptor binding and Glucose metabolism measured by PET.
National Institutes of Health Clinical Center, 9000 Rockville Pike
National Institutes of Health Clinical Center (CC)
Published on BioPortfolio: 2014-08-27T03:59:23-0400
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