Paroxysmal slow waves mark ictal networks

Epilepsy diagnosis and treatment monitoring are hindered by the episodic, heterogeneous expression of seizures and by normal-appearing scalp electroencephalography (EEG) in many patients. We previously described paroxysmal slow-wave events (PSWEs), brief epochs of broadband slowing detectable on EEG in people with epilepsy. In the present study, we sought to further define the clinical significance of this biomarker.

We used intracerebral and epidural recordings in a paraoxon rat model of temporal lobe epilepsy, as well as long-term video-EEG monitoring (LTM) in patients with temporal lobe epilepsy undergoing intracerebral recordings combined with scalp EEG, or with scalp EEG alone.

We show that PSWEs arise preferentially in temporo-frontal networks, co-occur with global slowing, and increase during both spontaneous and pharmacologically induced seizures. Epidurally recorded PSWEs were temporally coupled to deep temporal discharges and were bidirectionally modulated by γ-aminobutyric acid (GABA)ergic agents (increased with pentylenetetrazol and decreased with pentobarbital). In patients with temporal lobe epilepsy, simultaneous intracerebral recordings and scalp EEG showed that scalp PSWEs mirrored hippocampal spike-and-wave activity. PSWEs were more frequent during the preictal and ictal periods than during the interictal baseline, a finding confirmed in a retrospective analysis of 137 seizures from 18 patients recorded with scalp EEG alone.

These data indicate that surface PSWEs can index remote epileptiform activity and support their use as a quantitative, noninvasive biomarker for detecting EEG-silent deep foci and for pharmacodynamic evaluation.