High-frequency oscillations after acute hemorrhagic traumatic brain injury: insights into posttraumatic epilepsy development

Objective: The development of posttraumatic epilepsy after traumatic brain injury (TBI) is potentially identifiable by measuring biomarkers of epileptogenesis, namely pathological high-frequency oscillations (pHFOs). pHFOs are promising candidates, but it remains uncertain whether they can be detected early after TBI in clinical settings. This study was undertaken to determine the incidence and location of pHFOs as recorded from scalp and intracranial electroencephalography (EEG) during the first week after acute TBI and to determine the association of pHFOs with late posttraumatic seizures (PTS). Methods: We analyzed continuous EEG from 35 TBI patients with acute hemorrhagic TBI (Glasgow Coma Scale = 3–13) enrolled in the multicenter EpiBioS4Rx cohort. Automated pHFO detection was followed by independent experts' verification. The rate of two types of pHFO ripples (70–250 Hz) and fast ripples (250–500 Hz) were computed using scalp and intracranial EEG. Firth logistic regression models estimated associations between pHFOs rates and late PTS occurrence. Results: 16 of 35 patients (45.7%) developed late PTS. Verified scalp ripples were observed in 17 patients (48.6%), whereas no fast ripples were confirmed on expert review. Ripple activity was most frequent over frontal regions (13/17, 76.5%, p =.049, 95% confidence interval [CI] =.50–.93) and similarly frequent in perihemorrhagic locations (13/17, 76.5%, p =.049, 95% CI =.50–.93). Among 10 patients with intracranial EEG, verified ripples occurred in five (50%), including two of two with pericontusional strip electrodes. Significance: In critically ill patients with acute hemorrhagic TBI monitored in the intensive care unit, both scalp and intracranial EEG can detect pHFOs within the first week after injury, demonstrating the technical feasibility of capturing these signals in a real-world clinical setting. Verified pHFOs were most frequently observed over frontal and perihemorrhagic regions, consistent with early perilesional hyperexcitability. pHFOs appear to be mechanistically grounded markers of perilesional hyperexcitability. Standardized, high-sampling EEG studies with targeted pericontusional coverage are needed to establish prognostic performance for late PTS.