Scalp high-frequency activity differentiates neonates with seizures from healthy neonates and indicates postneonatal epilepsy risk

Objective: This study investigated whether scalp high-frequency activity (HFA) rates in neonates with seizures predict postneonatal epilepsy (PNE). It also assessed whether HFA rates differentiate neonates with seizures from healthy neonates and whether they vary by seizure etiology, therapeutic hypothermia, and electroencephalographic (EEG) background activity. Methods: We included 47 neonates with EEG-confirmed seizures (nine with neonatal mortality, three lost to follow-up, 35 with 1-year follow-up), and eight healthy neonates. Scalp HFA rates during sleep were determined using an automated detector. Results: Neonatal seizure etiologies included hypoxic-ischemic encephalopathy (HIE, n = 16), structural vascular lesions (SVL, n = 14), and neonatal onset genetic epilepsies (n = 14). Scalp HFA rates were significantly higher in neonates with seizures (.16 ± .15 HFA/min/channel [ch]) than in healthy neonates (.03 ± .02 HFA/min/ch), with a threshold of .06 HFA/min/ch best differentiating these groups. Among neonates with seizures, those with genetic etiologies had significantly higher HFA rates (.24 ± .19 HFA/min/ch) than those with SVL (.07 ± .05 HFA/min/ch). HFA rates were not associated with EEG background activity and were unaffected by therapeutic hypothermia in neonates with HIE. Of the 35 surviving neonates with seizures, 11 developed PNE, whereas 16 had normal development at follow-up. Neonates who developed PNE had significantly higher HFA rates (.27 ± .18 HFA/min/ch) than those with normal development (.11 ± .09 HFA/min/ch), with a threshold of .12 HFA/min/ch best differentiating these groups. Significance: Scalp HFA differentiates neonates with seizures from healthy neonates and may help identify those at higher risk for PNE. These findings support the potential use of scalp HFA as a potential biomarker for seizure monitoring and epilepsy risk stratification in neonates.