Abstracts

Rationale: Challenging the canonical stochasticity of seizures, studies of continuous electroencephalography (EEG) suggest that seizures preferentially occur during periods of heightened risk typified by pathologic brain activities, termed pro-ictal states. However, the presence of (pathologic) pro-ictal states amongst a plethora of otherwise physiologic (e.g., sleep-wake cycle) states has not yet been established.

Methods: We studied a prospective, consecutive series of 15 patients with temporal lobe epilepsy (TLE) who underwent limbic thalamic recordings in addition to routine (cortical) intracranial EEG for seizure localization. Pro-ictal (45 minutes prior to seizure onset) and inter-ictal (4 hours removed from all seizures) EEG was divided into 10-minute, non-overlapping windows, which were randomly distributed into training and validation cohorts in a 1:1 ratio. A deep neural classifier was applied to distinguish pro- from inter-ictal brain activities.

Results: A total of 1800 patient-hours of continuous thalamocortical EEG were analyzed. Statistically distinct (using a Bayes factor threshold of 200) pro-ictal states were detected in each subject. The median area under the receiver-operating-characteristic curve of the classifier was 0.92 (interquartile range [IQR], 0.96 to 0.90). Pro-ictal states were statistically distinguished at least 45 minutes prior to seizure onset in all but 2 subjects (in whom they were distinguished up to 35 minutes prior).

Conclusions: In the first human study of continuous thalamocortical EEG, we observed unequivocal evidence that pro-ictal states exist in TLE and can be detect more than one half-hour prior to seizure onset. The existence of non-physiologic brain states during periods of heightened seizure risk implies that adaptive neuromodulation therapies can be delivered at clinically meaningful horizons to potentially arrest ictogenesis.

Funding: None