Abstracts

Little is known about mechanisms of seizure cessation and the neurotransmitters involved. [¹¹C] diprenorphine (DPN) PET images all subtypes of opioid receptors. We have previously shown involvement of endogenous opioids in absence seizures provoked by hyperventilation, and in reading-induced seizures in reading epilepsy. Here, we investigate spontaneous complex partial seizures (CPS) in patients with temporal lobe epilepsy (TLE) and compare changes (compared to controls) with changes in patients having a first-ever secondarily generalized tonic-clonic seizure (2[deg]GTCS) following electroconvulsive therapy (ECT) for depression. We studied eight TLE patients 1.5-22h after the last spontaneous CPS and interictally. Four patients with severe depression were scanned prior to and four hours after their first 2[deg]GTCS following ECT. Eighteen healthy controls were studied for comparison, and test-retest variation established in fourteen. All 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 group comparisons performed correcting for global Vd. In the TLE patients, postictal decreases of [¹¹C] DPN Vd were seen in both thalami (Z=3.55, k=6968, p[sub]uncorr[/sub][lt]0.05) and medial frontal lobes (Z=3.24, k=16397, p[sub]corr[/sub][lt]0.07). Depressed patients showed decreases of [¹¹C] DPN Vd following ECT in the thalamus bilaterally (Z=3.67, k=6208, p[sub]uncorr[/sub][lt]0.03) and in both insular cortices (right, Z=4.29, k=24615, p[sub]corr[/sub][lt]0.004; left, Z=3.55, k=10470, p[sub]corr[/sub][lt]0.14). Our data is compatible with a release of endogenous opioids during both spontaneous CPS and electrically induced 2[deg]GTCS in the thalamus bilaterally, consistent with animal studies and case reports in humans of reduced seizure activity following intermittent electrical stimulation of the thalamus.
Endogenous anti-convulsant mechanisms may modulate abnormal network activity through thalamic release of opioids. Medial frontal changes in TLE patients could be a common endpoint for seizures starting in different parts of the temporal lobe and are compatible with previous SPECT studies of ictal blood flow. Changes in the insulae in ECT patients could be due to the site of onset of the electrically induced seizures. (Supported by Medical Research Council, National Society for Epilepsy)