Localization of the Epileptogenic Zone Using High Frequency Oscillations

Abstract

For patients with drug-resistant focal epilepsy, surgery is the therapy of choice in order to achieve seizure freedom. Epilepsy surgery foremost requires the identification of the epileptogenic zone (EZ), defined as the brain area indispensable for seizure generation. The current gold standard for identification of the EZ is the seizure-onset zone (SOZ). The fact, however that surgical outcomes are unfavorable in 40-50% of well-selected patients, suggests that the SOZ is a suboptimal biomarker of the EZ, and that new biomarkers resulting in better postsurgical outcomes are needed. Research of recent years suggested that high-frequency oscillations (HFOs) are a promising biomarker of the EZ, with a potential to improve surgical success in patients with drug-resistant epilepsy without the need to record seizures. Nonetheless, in order to establish HFOs as a clinical biomarker, the following issues need to be addressed. First, evidence on HFOs as a clinically relevant biomarker stems predominantly from retrospective assessments with visual marking, leading to problems of reproducibility and reliability. Prospective assessments of the use of HFOs for surgery planning using automatic detection of HFOs are needed in order to determine their clinical value. Second, disentangling physiologic from pathologic HFOs is still an unsolved issue. Considering the appearance and the topographic location of presumed physiologic HFOs could be immanent for the interpretation of HFO findings in a clinical context. Third, recording HFOs non-invasively via scalp electroencephalography (EEG) and magnetoencephalography (MEG) is highly desirable, as it would provide us with the possibility to translate the use of HFOs to the scalp in a large number of patients. This article reviews the literature regarding these three issues. The first part of the article focuses on the clinical value of invasively recorded HFOs in localizing the EZ, the detection of HFOs, as well as their separation from physiologic HFOs. The second part of the article focuses on the current state of the literature regarding non-invasively recorded HFOs with emphasis on findings and technical considerations regarding their localization.

Keywords: EEG; MEG; epilepsy; high-frequency oscillations; source localization.

Figure 1

Physiologic ripple rate results for bipolar channels recorded with DIXI electrodes, represented on the inflated cortex. Top: 95th percentile of the physiologic ripple rate per brain region. Bottom: rate of the individual channels, each dot represents a channel, the size and color indicates its ripple rate (left: lateral view, right: medial view). Source: Frauscher et al. (131) with permission from Wiley.

Figure 2

Depicted are examples from a 34 year old female patient undergoing presurgical evaluation including stereo EEG recording at the Montreal Neurological Institute and Hospital. She presented with a MRI-negative drug-resistent epilepsy and a seizure semiology suggestive of a right frontal and possible orbitofrontal generator. Scalp EEG with 25 electrodes recorded at a sampling frequency of 600 Hz showed interictal and ictal changes over right frontotemporal electrodes. Implantation showed continuous spiking over the lateral orbitofrontal region (electrode ROF 8–9). The patient underwent resection and is now seizure-free (Engel class 1) since 8 years. Neuropathology confirmed FCD IIb. Shown are a true ripple over Fp2-F10 contrasted to a muscle artifact over T10-P10 as well as a ripple and fast ripple recorded invasively at electrode ROF. All examples are given as filtered EEG signals at 80 or 250 Hz respectively, unfiltered signals, and time frequency plots. Note the isolated blobs in case of “true” HFOs.