Abstracts

Rationale: Childhood absence epilepsy (CAE) is characterized by seizures consisting of brief impairments of consciousness with bilaterally synchronous 3 Hz spike and wave discharges (SWD) on EEG. This study was undertaken to compare the cortical and subcortical contributions to the formation of early and mid-burst SWDs in patients with newly diagnosed and untreated CAE. The corticothalamic system plays a major role in the underlying pathophysiology of CAE. The purpose of this study was to use magnetoencephalography (MEG) to compare the thalamic and cortical contributions to the epileptic circuit in both the earliest (pre-ictal) and later (ictal) periods of the seizures.Methods: Children, aged 8 to 12 years old, with newly diagnosed and untreated CAE were recruited for the study. MEG recordings were conducted on a 275 channel CTF magnetometer and completed in 10 minute time blocks. MEG signal analysis was completed using sLORETA and Beamformer techniques. The first spike of each SWD burst was compared to a spike occurring 3 seconds later but within the same burst. Epochs of 25 milliseconds were analyzed starting from 50 milliseconds prior to spike of interest and for a total time interval of 300 milliseconds. An example of a single epoch can be seen in Figure 1.Results: Four children, aged 8 to 12 years old, with newly diagnosed and untreated CAE were recruited. A total of thirteen absence seizures occurred during MEG recording. Thalamic activity was seen with both source algorithms (Beamformer and sLORETA) and did not mirror the activity within the cortex, suggesting that it may be an independent generator. The thalamus, orbitofrontal cortex, and temporal cortex had the most prominent activity during the first spike (pre-ictal period) of the SWD burst. At this time, MEG activity within the thalamus oscillated and as the seizure progressed over the next 200 milliseconds more cortical areas were recruited. Variability in these patterns existed between subjects and also between seizures within the same subjects. Similar analysis with sLORETA on a spike that occurred 3 seconds into the SWD burst (ictal period) showed prominent focal, lateralized activity in the posterior-lateral frontal cortex. There was less intra-subject variability in these activation patterns (Figure 1). Conclusions: Using MEG, we have been able to detect focal areas of activity within the thalamus, orbitofrontal cortex, and temporal cortex during the earliest (pre-ictal) period of absence seizures in patients with untreated CAE. Similar analysis completed during the middle of the SWD burst (ictal period) showed focal and lateralized activation within the frontal cortex. The pre-ictal period demonstrated greater intra-subject variability than the ictal period suggesting that areas active during seizure onset may have individual patterns while the mechanisms which perpetuate the seizure may be more uniform. Further study will help to determine whether differences in pre-ictal patterns of activation may correlate with underlying pathogenesis or response to drug treatment.