Abstract
Introduction: High frequency oscillations (HFO) are promising biomarkers of epileptic tissue. While group analysis suggested a correlation between surgical removal of HFO generating tissue and seizure free outcome, HFO could not predict seizure outcome on an individual patient level. One possible explanation is the lack of differentiation between physiological and epileptic HFO. In the mesio-temporal lobe, a proportion of physiological ripples can be identified by their association with scalp sleep spindles. Spike associated ripples in contrast can be considered epileptic. This study investigated whether categorizing ripples by the co-occurrence with sleep spindles or spikes improves outcome prediction after surgery. Additionally, it aimed to investigate whether spindle-ripple association is limited to the mesio-temporal lobe structures or visible across the whole brain.Methods: We retrospectively analyzed EEG of 31 patients with chronic intracranial EEG. Sleep spindles in scalp EEG and ripples and epileptic spikes in iEEG were automatically detected. Three ripple subtypes were obtained: SpindleR, Non-SpindleR, and SpikeR. Rate ratios between removed and non-removed brain areas were calculated. We compared the distinct ripple subtypes and their rates in different brain regions, inside and outside seizure onset areas and between patients with good and poor seizure outcome.Results: SpindleR were found across all brain regions. SpikeR had significantly higher rates in the SOZ than in Non-SOZ channels. A significant positive correlation between removal of ripple-events and good outcome was found for the mixed ripple group (rs = 0.43, p = 0.017) and for ripples not associated with spindles (rs=0.40, p = 0.044). Also, a significantly high proportion of spikes associated with ripples were removed in seizure free patients (p = 0.036).Discussion: SpindleR are found in mesio-temporal and neocortical structures, indicating that ripple-spindle-coupling might have functional importance beyond mesio-temporal structures. Overall, the proportion of SpindleR was low and separating spindle and spike associated ripples did not improve outcome prediction in our patient group. SpindleR analysis therefore can be a tool to identify physiological events but needs to be used in combination with other methods to have clinical relevance.
Highlights
High frequency oscillations (HFO) are promising biomarkers of epileptic tissue
In total 2,291 intracranial video-EEG (iEEG) channels were analyzed, 187 of these were located in mesio-temporal structures, 2,104 in the neocortex
The observation that SpindleR occur in brain regions beyond the mesio-temporal areas will be relevant when it comes to understanding functional importance of ripple oscillations as well as using HFO as biomarkers in patients with epilepsy
Summary
High frequency oscillations (HFO) are promising biomarkers of epileptic tissue. While group analysis suggested a correlation between surgical removal of HFO generating tissue and seizure free outcome, HFO could not predict seizure outcome on an individual patient level. This study investigated whether categorizing ripples by the co-occurrence with sleep spindles or spikes improves outcome prediction after surgery. It aimed to investigate whether spindle-ripple association is limited to the mesio-temporal lobe structures or visible across the whole brain. HFO rates were repeatedly shown to be higher in the SOZ [5, 6, 10, 11] and the resection of HFO-generating areas correlated with a good postsurgical outcome in several studies [9, 12, 13]. The analysis of HFO co-occurring with spikes could improve the delineation of epileptogenic areas [16,17,18]
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