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Regional increases in [11C]flumazenil binding after epilepsy surgery
I Savic1, G Blomqvist, C Halldin
1Karolinska Institute, Dept of Neurology, Huddinge Hospital, Sweden.
Introduction:
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.
Conclusion:
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.
Insights
Epileptic seizures can alter benzodiazepine (BZ) receptor density in the brain. Following successful epilepsy surgery, BZ receptor binding normalized in some affected areas, suggesting these changes are dynamic and seizure-related.
Area of Science:
- Neuroscience
- Epileptology
- Radiology
Background:
- Animal studies indicate seizures affect neuro-receptor mRNA expression.
- Positron Emission Tomography (PET) with [11C]flumazenil reveals reduced benzodiazepine (BZ) receptor density in epileptogenic regions (ER) of epilepsy patients.
- BZ receptor reduction in ER correlates with seizure frequency, suggesting a link between seizure activity and receptor binding.
Purpose of the Study:
- To investigate if seizure activity alters BZ receptor binding.
- To determine if BZ receptor binding normalizes after seizure cessation.
Main Methods:
- PET scans using [11C]flumazenil measured BZ receptor density in 4 epilepsy patients before and 1 year after surgery.
- Analysis focused on mesial temporal lobe structures, epileptogenic regions, and projection areas, comparing pre- and post-surgical scans.
- Results were compared to data from 7 healthy controls using a computerized brain atlas.
Main Results:
- Pre-surgery PET showed reduced BZ receptor density in the ER and projection areas, with normal values in other cortical regions.
- Post-surgery, BZ receptor density normalized by 29+/-17% in several affected projection areas.
- Cortical regions not primarily affected by seizures showed unaltered BZ receptor density post-surgery.
Conclusions:
- Regional reductions in BZ receptor density appear dynamic and linked to seizure activity.
- These preliminary findings suggest that seizure-related changes in receptor binding are reversible.
- Further research is warranted to explore seizure-induced alterations in human regional receptor binding.