Elsevier

The Lancet

Volume 352, Issue 9132, 19 September 1998, Pages 952-955
The Lancet

Early Report
Focal cortical release of endogenous opioids during reading induced seizures

https://doi.org/10.1016/S0140-6736(97)09077-6Get rights and content

Summary

Background

Studies in animals implicate endogenous release of opioid peptides as a mechanism for terminating partial and generalised seizures. To localise dynamic changes in opioid neurotransmission associated with partial seizures and higher cognitive function, we investigated the release of endogenous opioids in patients with reading-induced seizures compared with healthy controls.

Methods

Five patients who had reading epilepsy and six controls had 11C-diprenorphine (DPN) positron-emissiontomography (PET) scans while reading a string of symbols (baseline) or a scientific paper (activation). Statistical parametric mapping was used to find areas with differences in opioid-receptor binding.

Finding

On activation scans mean 11C-DPN binding to opioid receptors was significantly lower (p<0·05 corrected for multiple non-independent comparisons) in the left parieto-temporo-occipital cortex (Brodmann area 37) in reading-epilepsy patients compared with controls.

Interpretation

These findings suggest that opioid-like substances are involved in the termination of reading-induced seizures.

Introduction

Cerebral glucose metabolism and regional cerebral blood flow reflect synaptic activity. 18F-fluorodeoxyglucose and 15O-H2O positron-emission tomography (PET) activation studies have increased our understanding of the functional anatomy of the brain in health and disease. The release of neurotransmitters, is a pivotal event in neuroregulation but has been very difficult to study non-invasively: PET studies have focused on pharmacological manipulations and changes in the number of receptors available to radioligands.1, 2, 3, 4

Studies have suggested that the release of opioid peptides is involved in the termination of seizures:5, 6, 7 in animals there is an increase in the number of δ-opioid receptor occupied after a seizure.8 Raised concentrations of leuenkephalin in the cerebrospinal fluid of epilepsy patients are indirect evidence of an endogenous opiate-receptor-mediated anticonvulsant system in human beings.9 Also, interictal PET studies have shown raised μ-opioid receptor binding in the lateral temporal neocortex adjacent to mesial temporal foci that suggest focal epilepsy may be associated with abnormal opioid transmission.10 A diffuse release of cerebral opioids, as evidenced by displacement of 11C-diprenorphine (DPN) binding has been seen in the cerebral-association cortex after repeated absence seizures.11

Reading epilepsy is a localisation-related reflex epilepsy in which seizures are usually myoclonic jerks restricted to the jaw or throat.12 Reading epilepsy is, therefore, an ideal model to study dynamic neurotransmitter changes in specific brain areas with focal seizure activity. The biochemical and anatomical bases of reading epilepsy are not well understood.13 Electroencephalogram (EEG) changes during seizures are predominantly seen in the temporo-parietal cortex of the language-dominant hemisphere but are also found in other cortical areas functionally activated by reading.14

Developments in the sensitivity of PET scanners and image analyses now allow measurement not only of the resting regional neuroanatomical distribution of opioid receptors but can also localise neurotransmitter release in response to focal epileptic activity and specific cognitive activation in man.15, 16 We measured acute changes in cerebral opioid-receptor availability during reading-induced seizures to investigate the neural networks and neurotransmitter release in this form of localised epilepsy and its specific trigger, reading.

Section snippets

Methods

Five right-handed patients with reading epilepsy and six age-matched, right-handed, healthy volunteers (controls) without a previous history of neurological or psychiatric disease had two 11C-DPN-PET scans, to measure μ-, k- and δ-opioid receptor availability. All patients had a diagnosis of reading epilepsy confirmed by video-EEG monitoring. A sixth patient had a secondary generalised seizure while he was reading before his first scan and was not studied because of the risk of other seizures.

Results

Patient details are shown in Table 1. Two patients were women. The median (range) age of the controls was 33 years (26–45). Reading induced frequent myoclonic jaw jerks (>20 seizures over 30 min) in two patients, less frequent seizures (<10 seizures) in two patients, and no visible or self-reported seizures in one patient. There were no differences in 11C-DPN binding on the baseline scans between patients and controls. Within an individual, there was no significant change in 11C-DPN binding for

Discussion

This is the first time that focal cortical release of neurotransmitters in response to specific brain activity has been shown in human beings. We found that, with reading, opioid-receptor binding in the left parieto-temporo-occipital cortex increases in controls and decreases in patients with reading epilepsy.

The left posterior temporal and the left inferior parietal cortex are known to be associated with word processing.22, 23 Price and colleagues24 reported increased blood flow to the left

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