Brain imaging shows epilepsy's deficit in serotonin

Positron emission tomography (PET) brain scans of a brain chemical messenger system may prove sensitive enough to help plan brain surgery for epilepsy, according to a study presented at the 130th annual meeting of the American Neurological Association in San Diego.

"Our preliminary data suggest that PET imaging with a marker that shows deficits in signaling for the neurotransmitter serotonin is more sensitive than the traditional PET measurement of brain glucose," said senior author William H. Theodore MD, chief of the Clinical Epilepsy Section at the National Institutes of Neurological Disorders and Stroke. When drugs fail to control epilepsy, brain surgery is often the only remaining therapeutic option.

However, identifying the correct spot for surgery has traditionally required a separate preliminary -- and inherently risky -- surgical procedure. Epilepsy is a chronic illness of the brain that is estimated to affect almost one percent of the U.S. population. During an epileptic seizure, nerve cells in the brain fire electrical impulses much faster than normal, often leading to loss of consciousness.and convulsionsIn a subset of cases, the seizures always begin the same, identifiable area of the brain, then spread to other areas.

Surgery to remove the area where seizures start can be safe and effective. "About 30% of patients with epilepsy, or approximately 600,000 people in the U.S., have seizures that are not controlled by antiepileptic drugs. Surgery may be an option for some of these, and localizing the epileptic focus is crucial," said Theodore. Both PET and magnetic resonance imaging (MRI) are under investigation as tools to guide neurosurgeons to areas of the brain where epileptic seizures originate.

Theodore and colleagues at NINDS have found, in their pilot study, that a marker for serotonin systems was able to identify epilepsy-generating brain areas even in a patient with a normal MRI. In related studies, the researchers have found that these deficits in serotonin correlate with the likelihood that patients with epilepsy will also suffer from depression.

Theodore cautions that this is a preliminary study of a procedure that is still in the research stages. However, he suggests that physicians should not hesitate to treat patients with epilepsy and depression with effective antidepressant drugs, and to refer patients for surgical evaluation if seizures are not controlled by antiepileptic drugs.

Serotonin 1A receptor imaging and temporal lobectomy. Robert Bonwetsch, MD, Giampiero Giovacchini, MD, Richard Carson, PhD, Patricia Reeves-Tyer, Kathy Kelley, MA, Peter Herscovitch, MD and William H Theodore, MD. Bethesda, Maryland. Positron emission tomography (PET) may provide supportive data for detecting epileptogenic zones in patients with temporal lobe epilepsy (TLE), helping to reduce the need for invasive EEG studies.

Serotonin (5HT) 1A receptor binding has been shown to be decreased in TLE. We used PET to compare 5HT-1A binding measured with the silent antagonist 18FCWAY, to glucose metabolism measured with 18FDG, in 19 patients who had temporal lobectomy for uncontrolled epilepsy, and a mean follow-up of 31 months. We analyzed PET data with co-registered MRI and partial volume correction, computing an asymmetry index (AI) using the formula [2] x [ipsilateral contralateral]/[ipsilateral + contralateral] for anatomic regions drawn on each patient s co-registered MRI scan.

Mean FDG asymmetry in the resected region was 0.25 0.18, versus 0.47 0.20 for FCWAY (P<0.001).>