Multicenter Comparison of Interictal HFO as a Predictor of Seizure Freedom (multiHFO)

Multicenter Comparison of Interictal High Frequency Oscillations as a Predictor of Seizure Freedom

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.

Study Overview

• Status: Enrolling by invitation
• Conditions: Epilepsy Intractable
• Intervention / Treatment: Diagnostic test: HFO analysis

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.

• Study Type: Observational
• Enrollment (Estimated): 300

Contacts and Locations

Study Locations

• Switzerland
  • ZH
    • Zurich, ZH, Switzerland, 8091
      • University Hospital Zurich, Neurosurgery

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• 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.

Description

Data as provided from the participating center

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
seizure freedom	ILAE grade 1	2 years after surgery
seizure recurrence	ILAE grade 2-6	within 2 years after surgery

Collaborators and Investigators

• Sponsor: University of Zurich
• Collaborators: Mayo Clinic; McGill University; University of Michigan; UMC Utrecht; University of Calgary; Thomas Jefferson University; St. Anne's University Hospital Brno, Czech Republic; Cook Children's Health Care System; Schweizerisches Epilepsie Zentrum

Publications and helpful links

General Publications

• 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.
• 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.
• 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.

Helpful Links

• HFO analysis: publications, algorithms and data

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2022
• Primary Completion (Estimated): May 1, 2024
• Study Completion (Estimated): May 1, 2024

Study Registration Dates

• First Submitted: April 10, 2022
• First Submitted That Met QC Criteria: April 10, 2022
• First Posted (Actual): April 18, 2022

Study Record Updates

• Last Update Posted (Estimated): December 7, 2023
• Last Update Submitted That Met QC Criteria: November 30, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Epilepsy; Seizures; Drug Resistant Epilepsy
• Other Study ID Numbers: multiHFO

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No