Are high-frequency oscillations better biomarkers of the epileptogenic zone than spikes?

Abstract

Purpose of review Precise localization of the epileptogenic zone is imperative for the success of resective surgery of drugresistant epileptic patients. To decrease the number of surgical failures, clinical research has been focusing on finding new biomarkers. For the past decades, high-frequency oscillations (HFOs, 80-500Hz) have ousted interictal spikes-the classical interictal marker-from the research spotlight. Many studies have claimed that HFOs were more linked to epileptogenicity than spikes. This present review aims at refining this statement in light of recent studies. Recent findings Analysis based on single-patient characteristics has not been able to determine which of HFOs or spikes were better marker of epileptogenic tissues. Physiological HFOs are one of the main obstacles to translate HFOs to clinical practice as separating them from pathological HFOs remains a challenge. Fast ripples (a subgroup of HFOs, 250-500Hz) which are mostly pathological are not found in all epileptogenic tissues. Summary Quantified measures of HFOs and spikes give complementary results, but many barriers still persist in applying them in clinical routine. The current way of testing HFO and spike detectors and their performance in delineating the epileptogenic zone is debatable and still lacks practicality. Solutions to handle physiological HFOs have been proposed but are still at a preliminary stage.

Kurtosis and skewness of high-frequency brain signals are altered in paediatric epilepsy

“…The findings of ripples (80–280 Hz) and fast ripples (250–600 Hz) in epilepsy have drawn a great attention from the researchers. In comparison to previous reports ( Zijlmans et al , 2012 ; Mooij et al , 2017 ; Frauscher et al , 2018 ; Lee et al , 2019 ; Roehri and Bartolomei, 2019 ), the major novel finding is the quantitative measurements of kurtosis and skewness of VE signals in epilepsy. Though additional verification and validation are necessary, building on the present study, we consider it is possible to determine the abnormalities of HFBS by measuring the kurtosis and skewness of signals.…”

“…Though HFOs are a well-recognized biomarker for epilepsy research ( Frauscher et al , 2017 ), the average population data have not yet been shown to be applicable to diagnosis of a single patient ( Jacobs et al , 2018 ; King-Stephens, 2019 ). One barrier hindering HFOs from wide clinical applications ( Engel et al , 2009 ; Roehri and Bartolomei, 2019 ) is that the brain generates both epileptic (pathological) and physiological HFOs. Physiological HFOs can be divided into elicited (functional) and endogenous HFOs.…”

“…Elicited HFOs have been widely studied as functional activation in the somatosensory, language and several other brain areas ( Xiang et al , 2001 ; Xiang et al , 2003 ). Endogenous HFOs were conventionally considered to be pathological, but an increasing list of reports indicates that endogenous HFOs can be physiological ( Engel et al , 2009 ; Roehri and Bartolomei, 2019 ). Since there is no one criterion that can quantitatively differentiate pathological HFOs from physiological HFOs, it is difficult to use HFOs in clinical practice ( Zijlmans et al , 2012 ; Mooij et al , 2017 ; Frauscher et al , 2018 ; Lee et al , 2019 ; Roehri and Bartolomei, 2019 ).…”

Amplitude of high frequency oscillations as a biomarker of the seizure onset zone

“…This measurement is also confounded by the occurrence of physiological HFOs, which are associated with healthy cognitive processing [36]. The characteristics of physiological and pathological HFOs are not fully understood and may overlap with one another [37,38]. Lastly, the detection method and parameters can affect the measurement of HFO rate.…”

High-frequency oscillations for the non-invasive localisation of the seizure onset zone

“…The lack of a standardised and clear process to distinguish between pathologic and physiological oscillations has limited the use of this type of electrographic oscillations as a clinical biomarker (Roehri and Bartolomei, 2019). The difficulty of distinguishing between both is evident when trying to classify HFOs according to their spectral frequencies, as both physiological and pathological HFOs share a similar frequency band (Jones et al, 2000, Fink et al, 2015.…”