Waveform sharpness identifies the morphological phenotype of high-frequency oscillation-associated spikes in pediatric focal epilepsy.

OBJECTIVE

Interictal spikes carrying high-frequency oscillations (HFOs) mark epileptogenic activity, but the waveform features that independently distinguish HFO-associated spikes from neighboring non-HFO spikes remain unclear. We examined which morphological domains distinguish them in children with focal epilepsy, while accounting for within-patient clustering.

METHODS

In this retrospective single-center study, we analyzed 993 interictal spikes (619 HFO-associated, 374 control) from 20 children with focal epilepsy, sampled within ± 5 s of visually validated scalp ripple-band (80-250 Hz) HFOs during NREM sleep. Four a priori domains-sharpness (steepness), peak-to-peak amplitude, slow-wave area, and duration-were compared using mixed-effects logistic regression with a patient random intercept and population-averaged generalized estimating equations (GEE), complemented by within-patient effect sizes (Cliff's δ).

RESULTS

Sharpness was by far the strongest independent correlate of HFO presence (adjusted odds ratio per 1-SD increase, 7.41 [95% CI 5.16-10.64] in the mixed-effects model and 5.31 [3.35-8.41] in the GEE model) and was higher in HFO-associated spikes in all 20 patients. Peak-to-peak amplitude was not independent of sharpness after adjustment, slow-wave area showed modest association that was attenuated when normalized to spike size, and duration was not a robust independent marker. Findings were consistent across alternative steepness metrics and both models.

CONCLUSIONS

HFO-associated spikes are defined primarily by waveform sharpness (steepness) rather than amplitude, consistent with sharpness reflecting the neuronal synchrony required for ripple generation.

SIGNIFICANCE: Waveform sharpness, obtainable from routine scalp EEG without dedicated HFO analysis, may provide a practical marker to enrich identification of HFO-likely epileptiform discharges.