Interictal Fast Ripples Are Associated With the Seizure-Generating Lesion in Patients With Dual Pathology

Jan Schönberger; Charlotte Huber; Daniel Lachner-Piza; Kerstin Alexandra Klotz; Matthias Dümpelmann; Andreas Schulze-Bonhage; Julia Jacobs

doi:10.3389/fneur.2020.573975

Interictal Fast Ripples Are Associated With the Seizure-Generating Lesion in Patients With Dual Pathology

Front Neurol. 2020 Sep 30:11:573975. doi: 10.3389/fneur.2020.573975. eCollection 2020.

Authors

Jan Schönberger^{1

2

3

4}, Charlotte Huber^{2

3}, Daniel Lachner-Piza^{1

3}, Kerstin Alexandra Klotz^{1

2

3

4}, Matthias Dümpelmann^{1

3}, Andreas Schulze-Bonhage^{1

3}, Julia Jacobs^{2

3

5

6}

Affiliations

¹ Epilepsy Center, Medical Center, University of Freiburg, Freiburg, Germany.
² Department of Neuropediatrics and Muscle Disorders, Medical Center, University of Freiburg, Freiburg, Germany.
³ Faculty of Medicine, University of Freiburg, Freiburg, Germany.
⁴ Berta-Ottenstein-Programme, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
⁵ Department of Paediatrics and Department of Neuroscience, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
⁶ Hotchkiss Brain Institute and Alberta Children's Hospital Research Institute, University of Calgary, Calgary, AB, Canada.

Abstract

Rationale: Patients with dual pathology have two potentially epileptogenic lesions: One in the hippocampus and one in the neocortex. If epilepsy surgery is considered, stereotactic electroencephalography (SEEG) may reveal which of the lesions is seizure-generating, but frequently, some uncertainty remains. We aimed to investigate whether interictal high-frequency oscillations (HFOs), which are a promising biomarker of epileptogenicity, are associated with the primary focus. Methods: We retrospectively analyzed 16 patients with dual pathology. They were grouped according to their seizure-generating lesion, as suggested by ictal SEEG. An automated detector was applied to identify interictal epileptic spikes, ripples (80-250 Hz), ripples co-occurring with spikes (IES-ripples) and fast ripples (250-500 Hz). We computed a ratio R to obtain an indicator of whether rates were higher in the hippocampal lesion (R close to 1), higher in the neocortical lesion (R close to -1), or more or less similar (R close to 0). Results: Spike and HFO rates were higher in the hippocampal than in the neocortical lesion (p < 0.001), particularly in seizure onset zone channels. Seizures originated exclusively in the hippocampus in 5 patients (group 1), in both lesions in 7 patients (group 2), and exclusively in the neocortex in 4 patients (group 3). We found a significant correlation between the patients' primary focus and the ratio R_{fast ripples}, i.e., the proportion of interictal fast ripples detected in this lesion (p < 0.05). No such correlation was observed for interictal epileptic spikes (p = 0.69), ripples (p = 0.60), and IES-ripples (p = 0.54). In retrospect, interictal fast ripples would have correctly "predicted" the primary focus in 69% of our patients (p < 0.01). Conclusions: We report a correlation between interictal fast ripple rate and the primary focus, which was not found for epileptic spikes. Fast ripple analysis could provide helpful information for generating a hypothesis on seizure-generating networks, especially in cases with few or no recorded seizures.

Keywords: dual pathology; epilepsy; fast ripples; high-frequency oscillations; interictal; stereotactic electroencephalography.