Interictal High Frequency Oscillations Detected with Simultaneous Magnetoencephalography and Electroencephalography as Biomarker of Pediatric Epilepsy

Abstract

Crucial to the success of epilepsy surgery is the availability of a robust biomarker that identifies the Epileptogenic Zone (EZ). High Frequency Oscillations (HFOs) have emerged as potential presurgical biomarkers for the identification of the EZ in addition to Interictal Epileptiform Discharges (IEDs) and ictal activity. Although they are promising to localize the EZ, they are not yet suited for the diagnosis or monitoring of epilepsy in clinical practice. Primary barriers remain: the lack of a formal and global definition for HFOs; the consequent heterogeneity of methodological approaches used for their study; and the practical difficulties to detect and localize them noninvasively from scalp recordings. Here, we present a methodology for the recording, detection, and localization of interictal HFOs from pediatric patients with refractory epilepsy. We report representative data of HFOs detected noninvasively from interictal scalp EEG and MEG from two children undergoing surgery.The underlying generators of HFOs were localized by solving the inverse problem and their localization was compared to the Seizure Onset Zone (SOZ) as this was defined by the epileptologists. For both patients, Interictal Epileptogenic Discharges (IEDs) and HFOs were localized with source imaging at concordant locations. For one patient, intracranial EEG (iEEG) data were also available. For this patient, we found that the HFOs localization was concordant between noninvasive and invasive methods. The comparison of iEEG with the results from scalp recordings served to validate these findings. To our best knowledge, this is the first study that presents the source localization of scalp HFOs from simultaneous EEG and MEG recordings comparing the results with invasive recordings. These findings suggest that HFOs can be reliably detected and localized noninvasively with scalp EEG and MEG. We conclude that the noninvasive localization of interictal HFOs could significantly improve the presurgical evaluation for pediatric patients with epilepsy.

Scalp ripples as prognostic biomarkers of epileptogenicity in pediatric surgery

“…Each ripple was reviewed on 80–160 Hz filtered (3‐sec/page) and unfiltered data (10‐sec/page). We excluded artifacts following previous guidelines . Events were discarded if they: (1) overlapped with cardiac beats on electrocardiography; (2) did not clearly stand out from surrounding background; or (3) showed very irregular morphology, high amplitude compared to background, or high amplitude/frequency variability .…”

“…ESI and MSI of ripples were performed on band‐pass filtered data (80‐160 HZ) using the wavelet Maximum Entropy on the Mean (wMEM) in Brainstorm , which allows localizing specific scales of interest. Data were down‐sampled to 640 Hz to ensure that the second scale corresponded to ripples (80–160 Hz) . Source localization was performed across each ripple time window.…”

“…Previous studies showed that noninvasively localized ripple generators correlate with regions generating interictal spikes or with different approximations of the EZ defined by clinical information . However, most of these studies included patients who did not necessarily undergo surgery, with the exception of two MEG studies on patients with focal MRI lesions or insular epilepsy .…”

Surgical resection of ripple onset predicts outcome in pediatric epilepsy

“…There are also intrinsic limitations of clinical iEEG. Future application of our methodology to full-coverage noninvasive techniques (ie, high-density EEG 46,49 and/or magnetoencephalography [47][48][49][50] can overcome these limitations and provide insights regarding ripple propagation before invasive implantation. Moreover, the coarse spatial sampling of clinical electrodes may undersample focal ripple activity, 44,45 and thus the recorded ripples may be the summed average of multiple spatially independent generators.…”

Magnetoencephalography: Clinical and Research Practices

“…As with adults, MEG is useful in both lesional and nonlesional cases [38,101], with particular utility in mapping spikes associated with tuberous sclerosis [53,55,56,57,102], cortical dysplasia [102,108] and other malformations [101,108]. HFOs have been successfully localized by MEG in children [71] and functional mapping of eloquent cortex may also be performed [50,102]. …”