Epileptogenicity Maps of Intracerebral Fast Activities (60–100 Hz) at Seizure Onset in Epilepsy Surgery Candidates

ORIGINAL RESEARCH published: 28 November 2019 doi: 10.3389/fneur.2019.01263 Epileptogenicity Maps of Intracerebral Fast Activities (60–100 Hz) at Seizure Onset in Epilepsy Surgery Candidates Anne-Sophie Job 1 , Olivier David 1,2*, Lorella Minotti 1 , Fabrice Bartolomei 2,3 , Stephan Chabardès 1 and Philippe Kahane 1 1 Inserm, U1216, CHU Grenoble Alpes, Grenoble Institut Neurosciences, Université Grenoble Alpes, Grenoble, France, 2 INS, Inserm, U1106, Marseille, France, 3 Neurophysiology Departement, La Timone Hospital, Marseille, France Edited by: Imad M. Najm, Cleveland Clinic, United States Reviewed by: Norberto Garcia-Cairasco, University of São Paulo, Brazil Stephan Schuele, Northwestern University, United States *Correspondence: Olivier David Specialty section: This article was submitted to Epilepsy, a section of the journal Frontiers in Neurology Received: 22 March 2019 Accepted: 13 November 2019 Published: 28 November 2019 Citation: Job A-S, David O, Minotti L, Bartolomei F, Chabardès S and Kahane P (2019) Epileptogenicity Maps of Intracerebral Fast Activities (60–100 Hz) at Seizure Onset in Epilepsy Surgery Candidates. Front. Neurol. 10:1263. doi: 10.3389/fneur.2019.01263 Frontiers in Neurology | www.frontiersin.org Fast activities (FA) at seizure onset have been increasingly described as a useful signature of the epileptogenic zone (EZ) in patients undergoing intracranial EEG recordings. Different computer-based signal analysis methods have thus been developed for objectively quantifying ictal FA. Whether these methods detect FA in all forms of focal epilepsies, whether they provide similar information than visual analysis (VA), and whether they might help for the surgical decision remain crucial issues. We thus conducted a retrospective study in 21 consecutive patients suffering from drug-resistant seizures studied by SEEG recordings. Ictal FA were quantified using the Epileptogenicity Maps (EM) method that we recently developed and which generates, by adopting a neuroimaging approach, statistical parametric maps of FA ranging from 60 to 100 Hz (FA60−100 ). Ictal FA were analyzed blindly using VA and EM, and the prognostic significance of removing areas exhibiting FA60−100 at seizure onset was evaluated. A significant ictal FA60−100 activation was found in all patients, and in 92.6% of all the 68 seizures recorded, whatever the epilepsy type. The overlap ratio (OR) between VA and EM was significantly better for defining the regions spared at seizure onset than those from which seizure arose (p < 0.001), especially in temporal or temporal “plus” epilepsies. EM and VA were much more discordant to define the EZ, with a mean number of electrode contacts involved at seizure onset significantly higher with EM than with VA (p = <0.0001). Seizure outcome correlated with the resection ratio for FA60−100 , which was significantly higher in seizure-free (Engel’s class Ia) than in non seizure-free patients (class Ic-IV) (p = 0.048). The quantification of FA at seizure onset can bring information additional to clinical expertise that might contribute to define accurately the cortical region to be resected. Keywords: epilepsy surgery, SEEG, epileptogenic zone, HFO, refractory epilepsy 1 November 2019 | Volume 10 | Article 1263 Job et al. Epileptogenicity Mapping INTRODUCTION MATERIALS AND METHODS The primary aim of epilepsy surgery is to remove the epileptogenic zone (EZ), i.e., the minimum amount of cortex that must be resected to produce seizure freedom. The identification of the EZ is a difficult process, which requires intracranial EEG (iEEG) recordings in 25–50% of the cases. However, even when using such iEEG information, epilepsy surgery still fails in a substantial ratio of patients (1). This means that iEEG criteria used for identifying the epileptogenic brain tissue are not clearly determined nor understood. Currently, iEEG demonstration of the seizure-onset zone—the cortical areas from where seizures start—offers a well-accepted approximation of the EZ. Traditionally, the identification of the EZ is done visually, and particular attention is paid on the classical low-voltage fast activity, which is the most characteristic iEEG seizure-onset pattern across all forms of focal epilepsies (2–4). By using signal analysis techniques, this pattern has been shown to be made of fast activities (FA) ranging from 20 to 200 Hz (5–13). Recent improvements in the acquisition technology have even shown that such activities can be as fast as 400 Hz (14) and even more (15). Importantly, the resection of brain regions exhibiting FA at seizure onset seems to predict a favorable surgical outcome (5, 11, 15–18). This paves the way to the development of quantitative FA-based indices to guide epilepsy surgery. In this context, an innovative method was proposed by the group of Marseille, where spectral and temporal information of stereotactic intracerebral EEG (SEEG) signals were mixed together to provide an index—named Epileptogenicity Index (EI)—quantifying the implication of each cortical site in seizure onset and early propagation (19). Keeping the same basic principles of EI determination during SEEG recordings, we proposed another quantification of epileptogenicity by adopting a neuroimaging approach in order to generate statistical parametric maps of FA, named Epileptogenicity Maps (EM) (7). The method is based on spectral analysis of FA ranging from 60 to 100 Hz at seizure onset (FA60−100 ) and the significantly activated electrodes (as compared to a baseline) are reported on the patient MRI to provide a 3-D anatomical map of seizure onset and propagation. Statistics can be performed at the group level, between seizures in the same patient or between patients suffering from the same type of epilepsy using normalization of brains to a common anatomical atlas. Such a quantification of FA60−100 was proved useful to provide clinicians with objective measurements and localization of the epileptic circuits (7, 20–23). However, whether the EM method reveals FA in any forms of focal epilepsies, whether it gives similar information as the traditional visual approach, and whether it helps to better delineate the EZ remain crucial issues. To this aim, we conducted a study in a series of 21 consecutive patients suffering from of drug-resistant focal epilepsy and who underwent a SEEG study before surgery. SEEG recordings were analyzed both visually and using the EM approach, and the prognostic significance of removing areas exhibiting FA60−100 at seizure onset was evaluated. This retrospective study was carried out in accordance with the recommendations of Direction de la Recherche Clinique of INSERM with written informed consent from all subjects or their representatives. The protocol was approved by the Comité d’Evaluation Ethique de l’INSERM IRB00003888 (protocol number 14-140). Frontiers in Neurology | www.frontiersin.org Inclusion Criteria For the purpose of this retr (...truncated)