High frequency oscillations in the intra-operative ECoG to guide epilepsy surgery (“The HFO Trial”): study protocol for a randomized controlled trial

Abstract

BackgroundIntra-operative electrocorticography, based on interictal spikes and spike patterns, is performed to optimize delineation of the epileptogenic tissue during epilepsy surgery. High frequency oscillations (HFOs, 80–500 Hz) have been identified as more precise biomarkers for epileptogenic tissue. The aim of the trial is to determine prospectively if ioECoG-tailored surgery using HFOs, instead of interictal spikes, is feasible and will lead to an equal or better seizure outcome.Methods\DesignWe present a single-blinded multi-center randomized controlled trial “The HFO Trial” including patients with refractory focal epilepsy of all ages who undergo surgery with intra-operative electrocorticography. Surgery is tailored by HFOs (arm 1) or interictal spikes (arm 2) in the intra-operative electrocorticography. Primary outcome is post-operative outcome after 1 year, dichotomized in seizure freedom (Engel 1A and 1B) versus seizure recurrence (Engel 1C-4). Secondary outcome measures are the volume of resected tissue, neurologic deficits, surgical duration and complications, cognition and quality of life. The trial has a non-inferiority design to test feasibility and at least equal performance in terms of surgical outcome. We aim to include 78 patients within 3 years including 1 year follow-up. Results are expected in 2018.DiscussionThis trial provides a transition from observational research towards clinical interventions using HFOs. We address methodological difficulties in designing this trial. We expect that the use of HFOs as a biomarker for tailoring will increase the success rate of epilepsy surgery while reducing resection volume. This may reduce neurological deficits and yield a better quality of life. Future technical developments, such as validated automatic online HFO identification, could, together with the attained clinical knowledge, lead to a new objective tailoring approach in epilepsy surgery.Trial registrationThis trial is registered at the US National Institutes of Health (ClinicalTrials.gov) #NCT02207673 (31 July 2014) and the Central Committee on Research Involving Human Subjects, The Netherlands #NL44257.041.13 (18 March 2014).

A method for the topographical identification and quantification of high frequency oscillations in intracranial electroencephalography recordings

“…Quantifying HFO rates using iEEG recordings from the epilepsy monitoring unit or operating room has been proposed as a means to identify epileptogenic brain regions (van ’t Klooster et al, 2015a, 2015b) and studies have suggested that simultaneous HFOs and inter-ictal epileptiform spikes (IES) are stronger indicators of epileptogenic tissue than IES events alone (Jacobs et al, 2008). A major challenge in the accurate evaluation of these biomarkers is that artifacts and sharp IESs can mimic HFOs when filtered.…”

Emergence of Narrowband High Frequency Oscillations from Asynchronous, Uncoupled Neural Firing

“…21, 22 There is much clinical evidence of their utility, 19, 35 and a clinical trial has begun, 36 making HFOs one of the most important potential biomarkers of epilepsy. They have been shown to delineate abnormal tissue, 20, 37–40 and thus have clear potential as a clinical tool to localize epileptic tissue spatially.…”

Automatic detection of high frequency oscillations during epilepsy surgery predicts seizure outcome

“…In order to implement the clinical use of HFOs, their value has yet to be confirmed in prospective fashion. The first small clinical trial (N=78), testing noninferiority of HFOs compared to interictal spikes during surgery, is currently being run (van 't Klooster et al , 2015a). Evidence for superiority of HFOs over spikes requires an international clinical trial with large numbers of patients, which will need fast, unsupervised and reliable automatic detection of HFOs.…”