Clinical trial NCT05332990: Multicenter Comparison of Interictal HFO as a Predictor of Seizure Freedom
Official title: Multicenter Comparison of Interictal High Frequency Oscillations as a Predictor of Seizure Freedom
Study type: OBSERVATIONAL
Overall status: ENROLLING_BY_INVITATION
Conditions: Epilepsy Intractable
Lead sponsor: University of Zurich
Sponsor class: OTHER
Collaborators: name: McGill University
name: University of Michigan
name: University of Calgary
name: Cook Children's Health Care System
name: St. Anne's University Hospital Brno, Czech Republic
name: Mayo Clinic
name: Thomas Jefferson University
name: UMC Utrecht
name: Schweizerisches Epilepsie Zentrum
First posted: 2022-04-18
Enrollment: 300
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: We include patients with drug-resistant focal epilepsy of all ages who 1) underwent invasive EEG recordings with subdural and/or depth electrodes as part of their pre-surgical evaluation 4, 2) underwent epilepsy surgery aiming at seizure freedom after resection of a single focus, and 3) and the postsurgical seizure outcome was determined by follow-up visits at ≥ 2 y 32. According to the International League Against Epilepsy (ILAE) Classification 3 we classify outcome into seizure freedom (ILAE 1) or recurrent seizures (ILAE 2-6). Outcome data that are assessed with the Engel scale are mapped to ILAE 1 or ILAE 2-6 respectively.

Brief summary: In drug-resistant focal epilepsy, interictal high frequency oscillations (HFO) recorded from intracranial EEG (iEEG) may provide clinical information for delineating epileptogenic brain tissue. The iEEG electrode contacts that contain HFO are hypothesized to delineate the epileptogenic zone; their resection should then lead to postsurgical seizure freedom.

We test whether our prospective definition of clinically relevant HFO is in agreement with postsurgical seizure outcome. The algorithm is fully automated and is equally applied to all datasets. The aim is to assess the reliability of the proposed detector and analysis approach.

Detailed description: We use an automated data-independent prospective definition of clinically relevant HFO that has been validated in data from two independent epilepsy centers. In this study, we combine retrospectively collected datasets from 9 independent epilepsy centers. The analysis is blinded to clinical outcome. We use iEEG recordings during NREM sleep with a minimum of 12 epochs of 5 minutes of NREM sleep. We automatically detect HFO in the ripple (80-250 Hz) and in the fast ripple (250-500 Hz) band. There is no manual rejection of events in this fully automated algorithm. The type of HFO that we consider clinically relevant is defined as the simultaneous occurrence of a fast-ripple and a ripple. We calculate the temporal consistency of each patient's HFO rates over several data epochs within and between nights. Patients with temporal consistency \< 50% are excluded from further analysis. We determine whether all electrode contacts with high HFO rate are included in the resection volume and whether seizure freedom (ILAE 1) was achieved at ≥2 y follow-up.

Applying a previously validated algorithm to a large cohort from several independent epilepsy centers may advance the clinical relevance and the generalizability of HFO analysis as essential next step for use of HFO in clinical practice.

Eligibility criteria: Data as provided from the participating center

Primary outcomes:
measure: seizure freedom
timeFrame: 2 years after surgery
measure: seizure recurrence
timeFrame: within 2 years after surgery
Secondary outcomes:
Other outcomes:
Locations:
city: Zurich
country: Switzerland
facility: University Hospital Zurich, Neurosurgery
state: ZH
Study officials:
References:
citation: Dimakopoulos V, Gotman J, Stacey W, von Ellenrieder N, Jacobs J, Papadelis C, Cimbalnik J, Worrell G, Sperling MR, Zijlmans M, Imbach L, Frauscher B, Sarnthein J. Protocol for multicentre comparison of interictal high-frequency oscillations as a predictor of seizure freedom. Brain Commun. 2022 Jun 9;4(3):fcac151. doi: 10.1093/braincomms/fcac151. eCollection 2022.
citation: Dimakopoulos V, Megevand P, Boran E, Momjian S, Seeck M, Vulliemoz S, Sarnthein J. Blinded study: prospectively defined high-frequency oscillations predict seizure outcome in individual patients. Brain Commun. 2021 Sep 2;3(3):fcab209. doi: 10.1093/braincomms/fcab209. eCollection 2021.
citation: Fedele T, Burnos S, Boran E, Krayenbuhl N, Hilfiker P, Grunwald T, Sarnthein J. Resection of high frequency oscillations predicts seizure outcome in the individual patient. Sci Rep. 2017 Oct 23;7(1):13836. doi: 10.1038/s41598-017-13064-1.