Abstracts

Rationale: High-frequency oscillations (HFOs), including ripples (R, 80-250 Hz) and fast ripples (FR, 250-500 Hz), are promising biomarkers of epileptic brain, yet detectability of scalp EEG HFOs—and especially FR—is still debated. We hypothesized that interictal scalp EEG HFOs are prevalent among children with epilepsy, and that FR can be seen in younger children with drug-resistant epilepsy. Methods: We identified 99 children who underwent Pediatric Epilepsy Monitoring Unit (EMU) admission at UCLA with EEG sampling frequency at 2000 Hz over a 16-month period. Two pediatric electroencephalographers experienced in HFO analysis and blinded to clinical information visually marked interictal scalp EEG HFOs (R and FR) in a 1 minute artifact-free sample during non-REM sleep. The identified events were adjudicated by a third electroencephalographer and further validated with time-frequency analysis. Results: There were 90 subjects (median age 49 months, range 1 month - 27 years; 51 males) analyzed for HFOs (9 subjects were excluded for analysis due to significant artifacts). At the time of the recording, 67 children (74%) had epilepsy. Interictal scalp HFOs were found in 24 children (27%) (examples in Figures 1 and 2), and all had epilepsy at the time of the recording, except one with R who had periventricular leukomalacia and presented with altered mental status (positive predictive value of HFOs for epilepsy was 96%). The prevalence of HFOs was much higher in children with epilepsy than children without epilepsy (34% vs. 4%, p=0.005). FR were found in 8 children, and all of them had either established drug-resistant epilepsy (5), new onset epileptic spasms (2), or new onset focal epilepsy with tuberous sclerosis complex (1). Children with FR were significantly younger than children with epilepsy without HFOs (median age 12.5 vs. 80.5 months, p=0.02), and children with R showed trends towards younger age (median age 29.0 months, p=0.07). Although HFOs were less sensitive than spikes in detecting epilepsy (34% vs 87%), HFOs were more specific (96% vs 87%). Conclusions: We have demonstrated that scalp EEG HFOs are prevalent among children with epilepsy, especially in younger children. Detectability of scalp EEG HFOs seems to be better in younger children, possibly due to thinner skull. Scalp EEG HFOs showed high positive predictive value and high specificity in detecting epilepsy, and may constitute a biomarker of epileptogenicity in younger children. Sensitivity of scalp EEG HFOs may be further enhanced by analyzing longer time-period by utilizing automatic detector. Funding: HN has received research support from the Susan Spencer Clinical Research Training Fellowship in Epilepsy from the American Academy of Neurology, with funding from the American Epilepsy Society, the American Brain Foundation, and the Epilepsy Foundation. JYW has received research funding from Novartis, GW Pharmaceutical, NINDS/NIH (R01 NS082649, U01 NS082320, U54 NS092090, U01 NS092595), and the Today’s and Tomorrow’s Children Fund from UCLA Mattel Children’s Hospital at the University of California Los Angeles.