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

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.

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).

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.

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

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