Recent studies have shown that non-linear analysis of intracranial activities can detect a ‘pre-ictal phase’ preceding the epileptic seizure. Nevertheless, the dynamical nature of the underlying neuronal process and the spatial extension of this pre-ictal phase still remain unknown. In this paper, we address these aspects using a new non-linear measure of dynamic similarity between different parts of intracranial recordings of nine patients with medial temporal lobe epilepsy recorded during transitions to seizure. Our results confirm that non-linear changes in neuronal dynamics allow, in most cases (16 out of 17), a seizure anticipation several minutes in advance. Furthermore, we show that the spatial distribution of pre-ictal changes often involves an extended network projecting beyond the limits of the epileptogenic region. Finally, the pre-ictal phase could frequently (13 out of 17) be characterized with a marked shift toward slower frequencies in upper delta or theta frequency range.

Key words: long-term non-stationarity, non-linear analysis, pre-ictal phase, seizure anticipation, temporal lobe epilepsy

We studied subdural recordings from a patient with an unusually focal and stable occipito-temporal epileptic discharge under four experimental conditions. The series of time intervals between successive spike discharges displayed a few (3–5) clusters of periodic values representing statistically significant short-term periodicities when tested against surrogate data. This short-term predictability was modulated during the different experimental conditions by periodicity shifts of the order of 15–30 ms. Correspondingly, there was an increased gamma-band (30–70 Hz) coherence between the epileptic focus and surrounding recording sites. We conclude that the focal epileptic activity is part of an extended network of neural activities which exert a fast modulation reflected in changes of transiently periodic activities.

Background: New methods derived from non-linear analysis of intracranial recordings permit the anticipation of an epileptic seizure several minutes before the seizure. Nevertheless, anticipation of seizures based on standard scalpelectroencephalographical (EEG) signals has not been reported yet. The accessibility to preictal changes from standard EEGs is essential for expanding the clinical applicability of these methods. Methods: We analysed 26 scalp-EEG/video recordings, from 60 min before a seizure, in 23 patients with temporal-lobe epilepsy. For five patients, simultaneous scalp and intracranial EEG recordings were assessed. Long-term changes before seizure onset were identified by a measure of non-linear similarity, which is very robust in spite of large artifacts and runs in real-time. Findings: In 25 of 26 recordings, measurement of non-linear changes in EEG signals allowed the anticipation of a seizure several minutes before it occurred (mean 7 min). These preictal changes in the scalp EEG correspond well with concurrent changes in depth recordings. Interpretation: Scalp-EEG recordings retain sufficient dynamical information which can be used for the analysis of preictal changes leading to seizures. Seizure anticipation strategies in real-time can now be envisaged for diverse clinical applications, such as devices for patient warning, for efficacy of ictal-single photon emission computed tomography procedures, and eventual treatment interventions for preventing seizures.

Background: New methods derived from non-linear analysis of intracranial recordings permit the anticipation of an epileptic seizure several minutes before the seizure. Nevertheless, anticipation of seizures based on standard scalpelectroencephalographical (EEG) signals has not been reported yet. The accessibility to preictal changes from standard EEGs is essential for expanding the clinical applicability of these methods. Methods: We analysed 26 scalp-EEG/video recordings, from 60 min before a seizure, in 23 patients with temporal-lobe epilepsy. For five patients, simultaneous scalp and intracranial EEG recordings were assessed. Long-term changes before seizure onset were identified by a measure of non-linear similarity, which is very robust in spite of large artifacts and runs in real-time. Findings: In 25 of 26 recordings, measurement of non-linear changes in EEG signals allowed the anticipation of a seizure several minutes before it occurred (mean 7 min). These preictal changes in the scalp EEG correspond well with concurrent changes in depth recordings. Interpretation: Scalp-EEG recordings retain sufficient dynamical information which can be used for the analysis of preictal changes leading to seizures. Seizure anticipation strategies in real-time can now be envisaged for diverse clinical applications, such as devices for patient warning, for efficacy of ictal-single photon emission computed tomography procedures, and eventual treatment interventions for preventing seizures.

Although considerable information on cellular and network mechanisms of epilepsy exists, it is still not understood why, how, and when the transition from interictal to ictal state takes place. The authors review their work on nonlinear EEG analysis and provide consistent evidences that dynamical changes in the neural activity allows the characterization of a preictal state several minutes before seizure onset. This new neurodynamical approach of ictogenesis opens new perspectives for studying the basic mechanisms in epilepsy as well as for possible therapeutic interventions.

Key words: EEG, ictogenesis, nonlinear analysis, seizure anticipation, synchronization

Epileptic seizures are a principal brain dysfunction with important public health implications, as they affect 0.8% of humans. Many of these patients (20%) are resistant to treatment with drugs. The ability to anticipate the onset of seizures in such cases would permit clinical interventions. The view of chronic focal epilepsy now is that abnormally discharging neurons act as pacemakers to recruit and entrain other normal neurons by loss of inhibition and synchronization into a critical mass. Thus, preictal changes should be detectable during the stages of recruitment. Traditional signal analyses, such as the count of focal spike density, the frequency coherence or spectral analyses are not reliable predictors. Non-linear indicators may undergo consistent changes around seizure onset. Our objective was to follow the transition into seizure by reconstructing intracranial recordings in implanted patients as trajectories in a phase space and then introduce non-linear indicators to characterize them. These indicators take into account the extended spatio-temporal nature of the epileptic recruitment processes and the corresponding physiological events governed by short-term causalities in the time series. We demonstrate that in most cases (17 of 19), seizure onset could be anticipated well in advance (between 2–6 minutes beforehand), and that all subjects seemed to share a similar “route” towards seizure.