Abstracts

This abstract is a recipient of the Young Investigator Award
This abstract has been invited to present during the Pediatric Epilepsy Highlights platform session

Rationale: Self-Limited Epilepsy with Centrotemporal Spikes (SeLECTS), the most common focal childhood epilepsy syndrome, is associated with frequent, sleep-potentiated interictal spike waves. Evidence suggests that SeLECTS subtly changes structural and functional brain connectivity. Whether spikes drive these connectivity differences remains an open question with important clinical implications. We aimed to: 1) compare connectivity between children with and without SeLECTS during sleep and wakefulness; and 2) assess the topology and duration of connectivity changes associated with spikes.

Methods: Electroencephalograms (EEGs) from 56 consecutively seen children with SeLECTS were segmented into periods with and without spikes. We measured connectivity between each electrode pair using the weighted phase lag index (wPLI) of the beta frequency band, a metric that is robust against volume conduction and able to estimate connectivity in short time periods. We focused our analyses on the average connectivity of each electrode with the other 18 electrodes. To examine whether SeLECTS leads to persistent alterations in connectivity, we compared connectivity during 500ms spike-free periods to connectivity measured in 65 age- and sex-matched controls. To understand the acute impact of spikes, we compared connectivity in 500ms epochs immediately before, during, and after spikes to connectivity during baseline, spike-free epochs. We explored whether behavioral state (awake/asleep), antiseizure medication use, or spike laterality affected spike-related connectivity._x000D_
Results: Children with SeLECTS had higher connectivity than controls specifically during sleep, where connectivity was elevated in 14 of the 19 electrodes. In contrast, connectivity in spike-free waking epochs did not differ from controls (Figure 1). Spikes were associated with widespread increases in connectivity across all electrodes, but were preceded and followed by focal connectivity increases in the left frontal and bicentral regions (Figure 2).  Specifically, connectivity in the pre-spike epoch was elevated from baseline at F3 (0.01, CI 0.005 to 0.02, p=0.002). In the post-spike epoch, connectivity was elevated at C3 (0.01, CI 0.005 to 0.02, p=0.0008), C4 (0.01, CI 0.004 to 0.02, p=0.0004), and F3 (0.01, CI 0.005 to 0.02, p=0.0009). While spike-associated connectivity increases did not differ based on antiseizure medication use or behavioral state, they did vary based on spike laterality. Specifically, right hemisphere connectivity increased more with right than left-lateralized spike waves.

Conclusions: Current therapies for SeLECTS do not target interictal spike waves. Spikes are associated with acute increases in connectivity and furthermore SeLECTS is associated with persistent connectivity elevations during sleep. Understanding whether acute spike-related changes induce this persistently elevated connectivity during sleep, and thus potentially structural and functional changes, will be critical to determine if spikes themselves should be a treatment target._x000D_

Funding: FMB receives funding for her research efforts from the NINDS K23NS116110.