Abstracts

Sleep deprivation has been identified as a factor influencing epileptic excitability in patients with seizure disorders, but the mechanism by which it increases epileptiform activity has not been identified. Adenosine (ADO) has been identified as having a protective role in reducing epileptiform activity, because it is associated with seizure termination; in vivo microdialysis studies have demonstrated that it rises following seizures in both animals and humans. The present study sought to determine whether changes in ADO level during sleep deprivation and ensuing sleep recovery may play a role in modulating changes in epileptiform activity.
Six male epilepsy patients (mean age = 28.7) were implanted with depth electrodes in order to provide diagnostic localizing information for surgery to relieve medically intractable seizures. Some depth electrodes were fitted with microdialysis probes in order to monitor changes in neurotransmitter release (artificial CSF flow rate = 1.0 ul/min). A total of 11 probes were implanted and were located in amygdala (7), hippocampus (2) and frontal cortex (2). Dialysate was collected at intervals of 10 to 30 min, and analyzed for ADO concentration with HPLC. Samples were collected from the final 3 hours of periods of sleep deprivation ranging from 36 to 40 hours, and from the first 3 hours of sleep recovery after completion of sleep deprivation.
An average of 8 samples were analyzed from each probe during sleep deprivation and 8 samples during sleep recovery. The mean sleep deprivation ADO level for 88 samples was 11.4 (SD=6.0)nM, and the mean sleep recovery ADO level for 89 samples was 10.1 (SD=5.4) nM. A t-test of the normalized means of all samples in each group showed no significant difference in ADO level between the two periods (t=0.89, df=174, N.S.), nor was there a difference between deprivation and sleep periods in the subset of 7 amygdala sites.
Although ADO has been shown to increase in response to seizures, the results of the present study indicate that ADO is not influenced by sleep deprivation or sleep recovery in amygdala or frontal cortex of patients with chronic seizures. This absence of change in ADO during sleep deprivation is in contrast to animal microdialysis studies in the basal forebrain which show increased ADO during sleep deprivation and decreases during sleep recovery. Although these results show no relationship between ADO and sleep deprivation, localized areas near irritative zones may show differences, or alternatively, ADO may not significantly influence interictal epileptiform activity.
[Supported by: NIH NS-02808 and Sleep Medicine Education and Research Foundation]