• Lancet neurology · Nov 2022

    Randomized Controlled Trial

    Intraoperative electrocorticography using high-frequency oscillations or spikes to tailor epilepsy surgery in the Netherlands (the HFO trial): a randomised, single-blind, adaptive non-inferiority trial.

    • Willemiek Zweiphenning, KloosterMaryse A van 'tMAV'Department of Neurology and Neurosurgery, Utrecht Brain Center, University Medical Center Utrecht (Part of ERN EpiCARE), Utrecht, Netherlands., Nicole E C van Klink, LeijtenFrans S SFSSDepartment of Neurology and Neurosurgery, Utrecht Brain Center, University Medical Center Utrecht (Part of ERN EpiCARE), Utrecht, Netherlands., Cyrille H Ferrier, Tineke Gebbink, Geertjan Huiskamp, van ZandvoortMartine J EMJEDepartment of Neurology and Neurosurgery, Utrecht Brain Center, University Medical Center Utrecht (Part of ERN EpiCARE), Utrecht, Netherlands., van SchooneveldMonique M JMMJDepartment of Pediatric Psychology, Wilhelmina's Children Hospital, University Medical Center Utrecht, Netherlands., M Bourez, Sophie Goemans, Sven Straumann, Peter C van Rijen, Peter H Gosselaar, Pieter van Eijsden, Willem M Otte, Eric van Diessen, BraunKees P JKPJDepartment of Neurology and Neurosurgery, Utrecht Brain Center, University Medical Center Utrecht (Part of ERN EpiCARE), Utrecht, Netherlands., Maeike Zijlmans, and HFO study group.
    • Department of Neurology and Neurosurgery, Utrecht Brain Center, University Medical Center Utrecht (Part of ERN EpiCARE), Utrecht, Netherlands.
    • Lancet Neurol. 2022 Nov 1; 21 (11): 982-993.

    BackgroundIntraoperative electrocorticography is used to tailor epilepsy surgery by analysing interictal spikes or spike patterns that can delineate epileptogenic tissue. High-frequency oscillations (HFOs) on intraoperative electrocorticography have been proposed as a new biomarker of epileptogenic tissue, with higher specificity than spikes. We prospectively tested the non-inferiority of HFO-guided tailoring of epilepsy surgery to spike-guided tailoring on seizure freedom at 1 year.MethodsThe HFO trial was a randomised, single-blind, adaptive non-inferiority trial at an epilepsy surgery centre (UMC Utrecht) in the Netherlands. We recruited children and adults (no age limits) who had been referred for intraoperative electrocorticography-tailored epilepsy surgery. Participants were randomly allocated (1:1) to either HFO-guided or spike-guided tailoring, using an online randomisation scheme with permuted blocks generated by an independent data manager, stratified by epilepsy type. Treatment allocation was masked to participants and clinicians who documented seizure outcome, but not to the study team or neurosurgeon. Ictiform spike patterns were always considered in surgical decision making. The primary endpoint was seizure outcome after 1 year (dichotomised as seizure freedom [defined as Engel 1A-B] vs seizure recurrence [Engel 1C-4]). We predefined a non-inferiority margin of 10% risk difference. Analysis was by intention to treat, with prespecified subgroup analyses by epilepsy type and for confounders. This completed trial is registered with the Dutch Trial Register, Toetsingonline ABR.NL44527.041.13, and ClinicalTrials.gov, NCT02207673.FindingsBetween Oct 10, 2014, and Jan 31, 2020, 78 individuals were enrolled to the study and randomly assigned (39 to HFO-guided tailoring and 39 to spike-guided tailoring). There was no loss to follow-up. Seizure freedom at 1 year occurred in 26 (67%) of 39 participants in the HFO-guided group and 35 (90%) of 39 in the spike-guided group (risk difference -23·5%, 90% CI -39·1 to -7·9; for the 48 patients with temporal lobe epilepsy, the risk difference was -25·5%, -45·1 to -6·0, and for the 30 patients with extratemporal lobe epilepsy it was -20·3%, -46·0 to 5·4). Pathology associated with poor prognosis was identified as a confounding factor, with an adjusted risk difference of -7·9% (90% CI -20·7 to 4·9; adjusted risk difference -12·5%, -31·0 to 5·9, for temporal lobe epilepsy and 5·8%, -7·7 to 19·5, for extratemporal lobe epilepsy). We recorded eight serious adverse events (five in the HFO-guided group and three in the spike-guided group) requiring hospitalisation. No patients died.InterpretationHFO-guided tailoring of epilepsy surgery was not non-inferior to spike-guided tailoring on intraoperative electrocorticography. After adjustment for confounders, HFOs show non-inferiority in extratemporal lobe epilepsy. This trial challenges the clinical value of HFOs as an epilepsy biomarker, especially in temporal lobe epilepsy. Further research is needed to establish whether HFO-guided intraoperative electrocorticography holds promise in extratemporal lobe epilepsy.FundingUMCU Alexandre Suerman, EpilepsieNL, RMI Talent Fellowship, European Research Council, and MING Fund.Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.

      Pubmed     Free full text   Copy Citation     Plaintext  

      Add institutional full text...

    Notes

     
    Knowledge, pearl, summary or comment to share?
    300 characters remaining
    help        
    You can also include formatting, links, images and footnotes in your notes
    • Simple formatting can be added to notes, such as *italics*, _underline_ or **bold**.
    • Superscript can be denoted by <sup>text</sup> and subscript <sub>text</sub>.
    • Numbered or bulleted lists can be created using either numbered lines 1. 2. 3., hyphens - or asterisks *.
    • Links can be included with: [my link to pubmed](http://pubmed.com)
    • Images can be included with: ![alt text](https://bestmedicaljournal.com/study_graph.jpg "Image Title Text")
    • For footnotes use [^1](This is a footnote.) inline.
    • Or use an inline reference [^1] to refer to a longer footnote elseweher in the document [^1]: This is a long footnote..

    hide…