[italic]IN-VIVO [/italic]EVIDENCE FOR ENDOGENOUS OPIOID RELEASE FOLLOWING SPONTANEOUS SEIZURES: AN [11]C-DIPRENORPHINE PET STUDY
Abstract number :
1.230
Submission category :
Year :
2003
Submission ID :
1050
Source :
www.aesnet.org
Presentation date :
12/6/2003 12:00:00 AM
Published date :
Dec 1, 2003, 06:00 AM
Authors :
Alexander Hammers, Marie-Claude Asselin, Rainer Hinz, David J. Brooks, John S. Duncan, Matthias J. Koepp Department of Clinical and Experimental Epilepsy, Insitute of Neurology, UCL, London, United Kingdom; Clinical Sciences Centre, MRC Cyclotron Building
To determine the role of endogenous neuropeptide release for the termination of spontaneous seizures in patients with refractory temporal lobe epilepsy (TLE).
We performed paired positron emission tomography (PET) studies with the non-specific opioid receptor ligand [11C] diprenorphine (DPN) in four patients with TLE: two patients with normal MRI (nMRI) and ictal left frontotemporal EEG changes, and two patients with right hippocampal sclerosis (rHS) and concordant ictal EEG changes in one, but contralateral ictal EEG changes in the other patient. The first DPN-PET scan (post-ictal) was performed between 1.5 and 15 hours after the last spontaneous complex partial seizure (CPS); the second PET scan (interictal) was performed after a seizure-free interval of 7 to 20 days. Eleven healthy controls were studied twice to establish test-retest variation. All subjects had high resolution MRI and quantitative [11C]-DPN PET on a Siemens/CTI ECAT HR++ scanner. Spectral analysis and metabolite-corrected arterial plasma input functions were used to produce parametric images of DPN volume-of-distribution (Vd). Individual parametric images were spatially normalised to a DPN template in standard stereotaxic space, using Statistical Parametric Mapping (SPM99) software, and difference images calculated. A reduction in DPN binding in the post-ictal PET scan would be suggestive of endogenous opioid release.
Test-retest variation of global DPN-Vd for the 11 controls was 0.33 [plusmn] 9.5% (range: -16.8% to +14.5%). All four patients showed post-ictally decreased opioid binding compared to baseline in the temporal lobe concordant with the side of ictal EEG abnormalities. Quantification of changes showed a 7 to 13% decrease in the presumed epileptogenic hippocampus post-ictally compared to baseline.
Our in-vivo findings of reduced opioid receptor binding are further evidence for endogenous opioid release following spontaneous seizures at critical sites in the brain involved in the termination of these seizures.
[Supported by: Medical Research Council and the National Society for Epilepsy]