Regional increases in [11C]flumazenil binding after epilepsy surgery.
BACKGROUND
Animal experiments suggest that epileptic seizures alter the expression of mRNA for neuro-receptors. PET measurements with [11C]flumazenil show that patients with partial seizures have a reduced density of benzodiazepine (BZ) receptors in the epileptogenic regions (ER) and some of the target areas for seizure activity, the so called projection areas. Recent data suggest that the degree of BZ receptor reduction in ER is correlated to seizure frequency. We therefore hypothesized that seizure activity can alter the BZ receptor binding, and that some of these changes could normalize when the seizures disappeared.


METHODS
In 4 patients whose seizures were generated by mesial temporal lobe structures, BZ receptor density was measured with [11C]flumazenil PET before, and 1 year after the epilepsy surgery and cessation of seizures. By use of a computerized anatomical brain atlas the same regions were analyzed in both PET scans, and the results related to data from 7 healthy controls.


RESULTS
Presurgical PET scans showed reductions in BZ receptor density in the epileptogenic region and some of its primary projection areas. Other cortical regions had normal values. Postsurgically, the calculated BZ receptor density normalized (29+/-17% increase) in several of the affected projection areas, whereas the values in other cortical regions remained unaltered.


CONCLUSIONS
Regional reductions in BZ receptor density may be dynamic and related to seizures. The present preliminary observations encourage further studies on seizure-related changes in regional receptor binding in humans.
Savic
I
I
Karolinska Institute, Dept of Neurology, Huddinge Hospital, Sweden.
Blomqvist
G
G
Halldin
C
C
Litton
J E
JE
Gulyas
B
B
D000328:Adult; D002250:Carbon Radioisotopes; D002540:Cerebral Cortex / Q000737:chemistry* / Q000000981:diagnostic imaging / Q000378:metabolism; D016001:Confidence Intervals; D004833:Epilepsy, Temporal Lobe / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000601:surgery*; D005260:Female; D005442:Flumazenil; D005500:Follow-Up Studies; D018757:GABA Modulators; D006801:Humans; D008297:Male; D019579:Neocortex / Q000737:chemistry / Q000000981:diagnostic imaging; D010865:Pilot Projects; D017397:Prefrontal Cortex / Q000737:chemistry / Q000000981:diagnostic imaging; D011336:Probability; D011869:Radioligand Assay; D011963:Receptors, GABA-A / Q000032:analysis / Q000378:metabolism*; D012640:Seizures / Q000000981:diagnostic imaging / Q000378:metabolism*; D013238:Stereotaxic Techniques; D013702:Temporal Lobe / Q000737:chemistry / Q000000981:diagnostic imaging; D014055:Tomography, Emission-Computed; D016896:Treatment Outcome
D002250:Carbon Radioisotopes; D018757:GABA Modulators; D011963:Receptors, GABA-A; D005442:Flumazenil