Candidates for epilepsy surgery must undergo presurgical evaluation to establish whether and how surgical treatment can stop seizures without causing neurological deficits. Various techniques, including MRI, PET, single-photon emission CT, video-EEG, magnetoencephalography and invasive EEG, aim to identify the diseased brain tissue and the involved network. Recent technical and methodological developments, encompassing both advances in existing techniques and new combinations of technologies, are enhancing the ability to define the optimal resection strategy. Multimodal interpretation and predictive computer models are expected to aid surgical planning and patient counselling, and multimodal intraoperative guidance is likely to increase surgical precision. In this Review, we discuss how the knowledge derived from these new approaches is challenging our way of thinking about surgery to stop focal seizures. In particular, we highlight the importance of looking beyond the EEG seizure onset zone and considering focal epilepsy as a brain network disease in which long-range connections need to be taken into account. We also explore how new diagnostic techniques are revealing essential information in the brain that was previously hidden from view.

Changing concepts in presurgical assessment for epilepsy surgery

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.

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Localization of the Epileptogenic Zone Using High Frequency Oscillations

OBJECTIVE To investigate whether high-frequency oscillations (HFOs) show spatiotemporal propagation and assess the relevance of the earliest oscillations in relation to the seizure onset zone (SOZ) and postsurgical outcome. METHODS We retrospectively investigated the intracerebral electroencephalography (EEG) of patients who became seizure free after subsequent surgery. We marked HFOs during 1 hour of recordings. We calculated the time delay between pairs of channels as the median delay between their HFOs and constructed a time line of the delay of each channel with respect to the earliest channel (first source channel). A network was defined when a temporal order could be established among the channels based on the existence of statistically significant delays. RESULTS Fifteen patients with good surgical outcome were included. We found ripple networks in all patients, and fast ripple networks in 9. For ripples, first source channels were found in a higher proportion in the SOZ than the rest of the network channels (15 of 27 [56%] versus 93 of 262 [35%]; p = 0.04). For both ripples and fast ripples, first source channels were resected more often that the rest of the network channels (ripples: 13 of 27 [48%] versus 65 of 262 [25%]; p = 0.01; fast ripples: 8 of 9 [89%] versus 17 of 40 [43%]; p = 0.002); channels with the highest rates of ripples and fast ripples were resected in a similar proportion. INTERPRETATION These results demonstrate that interictal HFOs are organized in networks and indicate a possible need for the resection of first source channels. However, resecting them is not superior to resecting channels with highest rates of HFOs. Ann Neurol 2019;85:485-494.

High-Frequency Oscillation Networks and Surgical Outcome in Adult Focal Epilepsy.

Intracranial electroencephalography (iEEG) has been the mainstay of identifying the seizure onset zone (SOZ), a key diagnostic procedure in addition to neuroimaging when considering epilepsy surger...

https://journals.sagepub.com/doi/pdf/10.1177/1535759720934852

Intracranial EEG in the 21st Century

Over the last decade, advances in genetics, neuroimaging and EEG have enabled the aetiology of epilepsy to be identified earlier in the disease course than ever before. At the same time, progress in the study of experimental models of epilepsy has provided a better understanding of the mechanisms underlying the condition and has enabled the identification of therapies that target specific aetiologies. We are now witnessing the impact of these advances in our daily clinical practice. Thus, now is the time for a paradigm shift in epilepsy treatment from a reactive attitude, treating patients after the onset of epilepsy and the initiation of seizures, to a proactive attitude that is more broadly integrated into a 'P4 medicine' approach. This P4 approach, which is personalized, predictive, preventive and participatory, puts patients at the centre of their own care and, ultimately, aims to prevent the onset of epilepsy. This aim will be achieved by adapting epilepsy treatments not only to a given syndrome but also to a given patient and moving from the usual anti-seizure treatments to personalized treatments designed to target specific aetiologies. In this Review, we present the current state of this ongoing revolution, emphasizing the impact on clinical practice.

Impact of predictive, preventive and precision medicine strategies in epilepsy.

Objective To evaluate the use of interictal high-frequency oscillations (HFOs) in epilepsy surgery for prediction of postsurgical seizure outcome in a prospective multicenter trial. Methods We hypothesized that a seizure-free outcome could be expected in patients in whom the surgical planning included the majority of HFO-generating brain tissue while a poor seizure outcome could be expected in patients in whom only a few such areas were planned to be resected. Fifty-two patients were included from 3 tertiary epilepsy centers during a 1-year period. Ripples (80–250 Hz) and fast ripples (250–500 Hz) were automatically detected during slow-wave sleep with chronic intracranial EEG in 2 centers and acute intraoperative electrocorticography in 1 patient. Results There was a correlation between the removal of HFO-generating regions and seizure-free outcome at the group level for all patients. No correlation was found, however, for the center-specific analysis, and an individual prognostication of seizure outcome was true in only 36 patients (67%). Moreover, some patients became seizure-free without removal of the majority of HFO-generating tissue. The investigation of influencing factors, including comparisons of visual and automatic analysis, using a threshold analysis for areas with high HFO activity, and excluding contacts bordering the resection, did not result in improved prognostication. Conclusions On an individual patient level, a prediction of outcome was not possible in all patients. This may be due to the analysis techniques used. Alternatively, HFOs may be less specific for epileptic tissue than earlier studies have indicated.

Andreas Schulze-Bonhage

Papers

Removing high-frequency oscillations: A prospective multicenter study on seizure outcome