Partial Epilepsy Clinical Trial
Official title:
PET Imaging of Serotonin Receptors in Seizure Disorders
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.
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