Abstracts

Rationale: Seizures and ictal-interictal continuum (IIC) activity may impact recovery from acute brain injury (ABI). Empiric antiepileptic drug (AED) intensification for electrophysiologic activity of uncertain significance is challenging to evaluate given structural neurologic deficits, variable pharmacodynamics, and potential sedative effects. We analyzed the EEG and electronic medical records to identify electrographic biomarkers predicting clinical response to AED therapy. Methods: We ascertained patients undergoing continuous electroencephalography (cEEG) during admission for ABI from a prospective big data repository of clinical data including regularly sampled Glasgow Coma Scale (GCS) scores and medication dose administration records. Frequency-specific spectral power (alpha 8-13 Hz, theta 4-7 Hz, and delta 0.5-4 Hz) and graph theoretical metrics of EEG functional connectivity were compared at time intervals before and after AED therapy. Results: 308 patients met inclusion criteria. 9,291 AED doses were administered (mean 1.64 +/- 0.96 unique AEDs per patient). Initiating the first AED was followed by a 0.44-point average improvement in GCS (p=4.32 x10-7); initiating a second or third AED yielded no significant change, and adding a fourth, fifth, or sixth AED was followed by a 0.69-point worsening in GCS (p=0.044). Improvement in GCS 6 hours after AED administration was heralded by decline in EEG delta power and rise in network density in the hour following treatment. Decline in GCS was heralded by an early rise in delta power and decline in network density. Patients with the highest tertile of EEG improvement (greatest combination of rising EEG density and declining delta power) had a consistently improving GCS trajectory in the 48 hours following medication administration, whereas those in the lowest tertile had a consistently worsening GCS trajectory. Conclusions: Empirically intensifying AED treatment for disorders of consciousness after ABI has diminishing benefit after the initial agent. Quantitative EEG biomarkers of early treatment response appears to robustly predict clinical response following AED treatment. Funding: This work was supported by NIH/NINDS grant R25 NS065743 (Rubin) and NIH/NINDS grant K23 NS105950 (Rosenthal)