The neuroanatomical and pathophysiological basis of primary generalised absences is uncertain. Administration of endogenous
opioids has been shown to result in absence-like
seizures in animal models. Positron emission tomography scans were performed in eight patients with primary generalised
epilepsy and eight control subjects. Regional cerebral blood flow was measured interictally with C15O2, after which a 90 minute dynamic study with the
opioid-receptor ligand 11C-diprenorphine was performed. Serial absences were precipitated by
hyperventilation for 10 minutes, starting 30-40 minutes after injection of
diprenorphine. Absences, with generalised spike-wave discharges on the EEG, occurred for between 10% and 51% of the provocation period. No individual (normal or patient) had any interictal focal abnormalities of cerebral blood flow. After provocation of serial absence
seizures, there was increased
diprenorphine elimination from the association cortex, but not from the thalamus, basal ganglia, or cerebellum, compared with control subjects and patients scanned without provocation of absences. It was possible to 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 constant (k3). These results suggest that endogenous
opioids are released in the association cortex at the time of serial absences, lead to increased receptor occupancy, and may have an important role in the pathophysiology of generalised absences.