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.
Highlights
Despite more than 30 antiepileptic medication available on the market (1, 2), about 30–40% of patients treated for epilepsy continue to have seizures (3)
The fact, that surgical outcomes are unfavorable in 40–50% of well-selected patients (8), suggests that the seizure-onset zone (SOZ) is a suboptimal biomarker of the epileptogenic zone (EZ), and that new biomarkers resulting in better postsurgical outcomes are needed
With the present article we aimed to provide a comprehensive overview of the current state of high-frequency oscillations (HFOs) research in epilepsy
Summary
Despite more than 30 antiepileptic medication available on the market (1, 2), about 30–40% of patients treated for epilepsy continue to have seizures (3). The possible value of HFOs recorded interictally is of special interest, as this does not require to record seizures, a process which is time and resource consuming, and bearing the risk of complications due to secondary generalization after lowering the patients’ antiepileptic drugs This notion of interictal HFOs as a possible biomarker for the EZ has tipped the scale to further pursue their investigation. There are physiologic, non-epileptic HFOs and their existence poses a challenge, as disentangling them from clinically relevant pathologic HFOs still is an unsolved issue with considerable influence on HFO research (26–30) Such a distinction is crucial to further investigate the clinical value of HFOs in predicting outcome after epilepsy surgery. This article focuses on findings of pathologic HFOs recorded non-invasively, and discusses technical considerations regarding localization of HFOs
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