Authors :
Presenting Author: Ji Yeoun Yoo, MD – Icahn School of Medicine at Mount Sinai, New York City
Katie Bullinger, MD, PhD – Emory University School of Medicine
Lise Johnson, PhD – NeuroPace, Inc.
Martha Morrell, MD – NeuroPace
Rationale: Lennox-Gastaut syndrome (LGS) is a symptomatic generalized epilepsy consisting of intellectual disability and intractable seizures with multiple seizure types. Ictal scalp EEG patterns in LGS are well described and can include diffuse decrement, generalized spike and wave discharges, generalized rhythmic/fast activity or focal patterns. However, the intracranial EEG (iEEG) correlates of these patterns are unknown. Leveraging data from the RNS System trial in LGS (NCT05339126), we explore iEEG patterns in the prefrontal cortex and centromedian nucleus (CM) of the thalamus and the correlation between scalp and iEEG during ictal events.
Methods: All participants in the parent trial were implanted with two RNS System devices bilaterally; depth leads were targeted at CM and cortical strip (Cx) leads were placed over the prefrontal cortex. Five trial participants were enrolled in a sub-study examining simultaneous scalp EEG and iEEG recordings. Participants were asked to swipe the RNS System magnet over the neurostimulators to mark any clinical seizures. iEEG recorded by both devices was synchronized to scalp EEG using stimulation artifacts.
Results:
Of the 5 participants, 4 had clinically evident ictal events. Each participant exhibited a different clinical seizure type including tonic, atonic, absence, and myoclonic. A total of 16 seizures were captured simultaneously by the RNS System(s) and scalp EEG. The RNS System detected ictal activity in every seizure, and the seizure onset was captured by at least one of the two devices in 15 of the 16. For 2 of 3 myoclonic seizures, the onset in CM preceded the onset in Cx; onset for the third was near simultaneous. The onset pattern in Cx was alpha/theta or poly-spike and wave, and in CM was rhythmic alpha/theta. In the 5 tonic seizures and the 2 atonic seizures, gamma activity in the Cx onset preceded onset in the CM. The 5 absence seizures also showed gamma in the Cx, but there was no apparent change in the CM prior to the stimulation onset.
When seizure onsets were captured by both RNS Systems, the onsets were not typically simultaneous. Ictal activity recorded from the Cx leads was often simultaneous with or preceded onset in the scalp EEG. In contrast, onset on the CM channels was often delayed with respect to the scalp EEG, with the exception of myoclonic seizures.
Conclusions: Seizure onset patterns varied by seizure type. These variable iEEG seizure onset patterns suggest that potential iEEG biomarkers may differ by clinical seizure type. Additionally, findings of earlier onset on the scalp/cortex for some seizure types (tonic, atonic, absence) support initiation of seizures in cortical regions and the existence of a ‘cortical hotspot’ (Warren et al, 2024). Myoclonic seizures may have a source distinct from this hotspot.
Funding: Research reported in this publication was supported by the National Institute of Neurological Disorders and Stroke of the National Institutes of Health under Award Number UH3NS109557. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.