Abstracts

Rationale:
Identifying the epileptogenic zone (EZ) is a key issue in the surgical management of drug-resistant epilepsy. Stereoelectroencephalography (SEEG) generally involves implanting 10 to 15 depth electrodes to help locate the EZ. While the primary aim of SEEG is to record epileptic seizures, it can also help to record "fast-ripples" (FR), high-frequency brief oscillations (200-600 Hz, duration about 10 ms), which could be a relevant biomarker of the EZ in the interictal period. FR, whose generators are very local, have mainly been studied using standard depth electrodes or grids to date. Recent studies have questioned the performance of FR as a biomarker. The FR analyzed in these studies were recorded with macroelectrodes however, while FR were initially identified using microelectrodes. In addition, some studies suggest that more FR are recorded using micro- than macroelectrodes. The development of intracerebral hybrid electrodes equipped with tetrodes, enabling the recording of brain activity at both micrometric and millimetric scales simultaneously in exactly the same location, could help improve the detection and characterization of FR, and possibly their interest as biomarkers. Here, our hypothesis was that more fast-ripples would be recorded at the micro- than at the macro-scale.

Methods:
This feasibility study focuses on the bicentric (Toulouse University Hospital & Lyon Civil Hospices) EPIFAR cohort (ClinicalTrial: NCT02491476; 2015-2022) consisting of 54 patients with epilepsy candidates for SEEG in whom 3 or 4 standard macroelectrodes were replaced by DIXI Medical MME electrodes, hybrid micro-macroelectrodes equipped with 2 or 3 tetrodes (4 microwires – diameter, 20 microns each). We quantitatively compared the detection of FR at each spatial scale and evaluated their occurrence according to the recording sites (epileptogenic zone, irritative zone and presumed healthy zone). FR were quantified using Halyzia, a semi-automatic method developed in our team. Determination of the different zones was performed by clinicians blind to the fast-ripple results.

Results:
A total of 205 hybrid electrodes were implanted in 54 patients, covering different cerebral locations and with various etiologies. Intra-patient comparative results indicate a higher rate of FR detected by tetrodes than by macrocontacts, in most instances with a highly significant effect size, with a preponderance of FR in the EZ. However, FR were also sometimes recorded in the irritative zone. FR were recorded in some patients only on the micro-electrodes. Not all patients had FR. FR characteristics in terms of morphology, complexity and spatial extent could vary between spatial scales.

Conclusions:
This feasibility study illustrates the potential clinical interest of integrating multiscale recordings into the pre-surgical assessment of epilepsy. These results question our knowledge about fast-ripples and raise a debate about the usefulness of micro-electrodes in clinical practice.

Funding: European Research Council (FP/2007-2013) / ERC no. 323711 (M4 project), FFRE (Prix Marion Clignet), FRC, Toulouse University Hospital (APITO).