INVESTIGATION OF THE OPIOID SYSTEM IN ABSENCE SEIZURES WITH POSITRON EMISSION TOMOGRAPHY

The neuroanatomical and pathophysiological basis of primary generalise d absences is uncertain. Administration of endogenous opioids has been shown to result in absence-like seizures in animal models. Positron e mission tomography scans were performed in eight patients with primary generalised epilepsy and eight control subjects. Regional cerebral wa s measured interictally with (CO2)-O-15, after which a 90 minute dynam ic study with the opioid-receptor ligand C-11-diprenorphine was perfor med. Serial absences were precipitated by hyperventilation for 10 minu tes, starting 30-40 minutes after injection of diprenorphine. Absences , with generalised spike-wave discharges on the EEG, occurred for betw een 10% and 51% of the provocation period. No individual (normal or pa tient) had any interictal focal abnormalities of cerebral blood flow. After provocation of serial absence seizures, there was increased dipr enorphine elimination from the association cortex, but not from the th alamus, basal ganglia, or cerebellum, compared with control subjects a nd patients scanned without provocation of absences. It was possible t o simulate the observed increased diprenorphine elimination following seizures in cerebral cortex using a two tissue compartment model, with an estimated 15-41% decrease in the specific tracer uptake rate const ant (k(3)) These results suggest that endogenous opioids are released in the association cortex at the time of serial absences, lead to incr eased receptor occupancy, and may have an important role in the pathop hysiology of generalised absences.