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third of patients implying the presence of more widespread abnormalities than previously
thought163-165.

Quantitative autoradiographic and neuropathological studies of resected HS showed that
cBZR density (Bmax) was reduced in the CA1 subregion of the hippocampus, over and above
the loss of receptors that was attributable to neurone loss. In other hippocampal subregions,
loss of receptors paralleled loss of neurones and increases in affinity were noted in the
subiculum, hilus and dentate gyrus166. A direct comparison of quantitative in vivo
hippocampal 11C-FMZ binding and ex vivo quantitative 3H-FMZ autoradiographic studies
showed a mean 42% reduction of the two measures in patients with HS and a good correlation
in individual patients167.

Utility of 11C-flumazenil PET in the investigation of epilepsy
It seems most likely that cBZR changes reflect localised neuronal and synaptic loss in the
epileptogenic zone and that the more extensive hypometabolism is a result of diaschisis. In
clinical terms, 11C-FMZ PET may be superior to 18FDG for the localisation of the source of
the seizure. These data do not confer additional clinically useful information in patients with
clear-cut MRI findings of unilateral HS. In a clinical series of 100 patients with partial
seizures having pre-surgical evaluation, 94% of those with TLE had an abnormality of 11C-
FMZ PET detected, as did 50% of those with other forms of partial epilepsy; 81% of
abnormalities found using 11C-FMZ PET were concordant with abnormalities on MRI. 11C-
FMZ PET was useful in the identification of bilateral temporal lobe pathology168.

11C-FMZ PET is likely to be most useful in conditions in which the epileptogenic area is
difficult to define by other means, i.e. patients with focal epilepsy and normal high quality
MRI (‘MRI-negative’) and patients with epilepsy due to malformations of cortical
development.

Opioid receptors

Endogenous opioids are released following partial and generalised tonic-clonic seizures and
contribute to the post-ictal rise in seizure threshold. Investigations of opioid receptors in
patients with TLE have shown an increase of the binding of the specific mu-agonist 11C-
carfentanil to mu-receptors in lateral temporal neocortex, reflecting an increase in number of
available receptors or increased affinity. It has been speculated that an increase in mu-opioid
receptors in the temporal neocortex may be a manifestation of a tonic antiepileptic system
that serves to limit the spread of electrical activity from other temporal lobe structures169.

Dynamic ictal studies of opioid receptors have been carried out in reading epilepsy, using
11C-diprenorphine. In order to localise dynamic changes of opioid neurotransmission
associated with partial seizures and higher cognitive function, release of endogenous opioids
in patients with reading epilepsy was compared with that in healthy volunteers170. Reading-
induced seizures were associated with reduced 11C-diprenorphine binding to opioid receptors
in the left parieto-temporo-occipital cortex and to a lesser extent the left middle temporal
gyrus and the posterior parieto-occipital junction. These data gave evidence for localised
endogenous opioid peptide release during seizures induced by reading and demonstrate the
potential of PET to image release of specific neurotransmitters in response to brain activity
in specific cerebral areas in vivo.

NMDA receptor

11C-(S)-[N-methyl]ketamine binds to the NMDA receptor, and is thus of interest in studies
of epilepsy. In eight patients with medial TLE there was a reduction in tracer binding that