Epileptogenicity of brain structures in human temporal lobe epilepsy: a quantified study from intracerebral EEG

doi:10.1093/brain/awn111 Brain (2008), 131, 1818 ^1830 Epileptogenicity of brain structures in human temporal lobe epilepsy: a quantified study from intracerebral EEG Fabrice Bartolomei,1,2,3 Patrick Chauvel1,2,3 and Fabrice Wendling4,5 1 INSERM, U751, Marseille, F-13000, 2Aix Marseille Universite¤, Faculte¤ de Me¤decine, Marseille, F-13000, Assistance Publique ^ Ho“pitaux de Marseille, Ho“pital de la Timone, Service de Neurophysiologie Clinique, Marseille, F-13000, 4INSERM, U642, Rennes, F-35000 and 5Universite¤ de Rennes 1, LTSI, Rennes, F-35000, France 3 Correspondence to: Fabrice Bartolomei, Ho“pital de la Timone, Service de Neurophysiologie Clinique, 264 Rue Saint-Pierre, Marseille 13005, France E-mail: The identification of brain regions generating seizures (‘epileptogenic zone’, EZ) in patients with refractory partial epilepsy is crucial prior to surgery. During pre-surgical evaluation, this identification can be performed from the analysis of intracerebral EEG. In particular, the presence of high-frequency oscillations, often referred to as ‘rapid discharges’, has long been recognized as a characteristic electrophysiological pattern of the EZ. However, to date, there has been no attempt to make use of this specific pattern to quantitatively evaluate the degree of epileptogenicity in recorded structures. A novel quantitative measure that characterizes the epileptogenicity of brain structures recorded with depth electrodes is presented. This measure, called ‘Epileptogenicity Index’ (EI), is based on both spectral (appearance of fast oscillations replacing the background activity) and temporal (delay of appearance with respect to seizure onset) properties of intracerebral EEG signals. EI values were computed in mesial and lateral structures of the temporal lobe in a group of 17 patients with mesial temporal lobe epilepsy (MTLE). Statistically high EI values corresponded to structures involved early in the ictal process and producing rapid discharges at seizure onset. In all patients, these high values were obtained in more than one structure of the temporal lobe region. In the majority of patients, highest EI values were computed from signals recorded in mesial structures. In addition, when averaged over patients, EI values gradually decreased from structure to structure. For lateral neocortex, higher EI values were found in patients with normal MRI, in contrast with patients with hippocampal sclerosis. In this former sub-group of patients, a greater number of epileptogenic structures was also found. A statistically significant correlation was found between the duration of epilepsy and the number of structures disclosing high epileptogenicity suggesting that MTLE is a gradually evolving process in which the epileptogenicity of the temporal lobe tends to increase with time. Keywords: partial epilepsy; high-frequency oscillations; epileptogenic zone; seizure onset Abbreviations: EC = entorhinal cortex; EI = epileptogenicity index; EZ = epileptogenic zone; HS = hippocampal sclerosis; MRI = magnetic resonance imaging; MTLE = mesial temporal lobe epilepsy; STG = superior temporal gyrus Received January 20, 2008. Revised April 3, 2008. Accepted May 12, 2008. Advance Access publication June 13, 2008 Introduction Over the past decades, a sustained research effort has been undertaken to localize and to characterize the cerebral areas involved in the genesis and the propagation of focal epileptic seizures. Indeed, the identification of the so-called ‘epileptogenic zone’ (EZ) (Bancaud et al., 1965), usually defined as the subset of brain sites involved in the generation of seizures, is crucial in the context of epilepsy surgery as the aim of the surgical procedure is precisely to remove the EZ. The non-negligible rate of failure in epilepsy surgery brings evidence that the question of the definition of the epileptogenic zone is still unsolved and that progress must still be made in order to determine the epileptogenicity of the brain regions in a patient-specific context. One puzzling feature is that brain activity at seizure onset may disclose complex electrophysiological patterns, often with the involvement of several distinct structures. Therefore, in a large number of cases, this typical observation shows that the EZ can hardly be described as ß The Author (2008). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: Quantified epileptogenicity in TLE a simple epileptic focus (Bartolomei et al., 2001a, 2005; Spencer, 2002). For clinicians facing the problem of the definition of the EZ from the analysis of intracerebral EEG signals, two parameters are generally considered in order to qualitatively determine the degree of ‘epileptogenicity’ of a given structure and its subsequent contribution to the EZ. The first parameter is the capability of a given structure to generate high-frequency oscillations, typically in the beta or/and the gamma range. These oscillations are classically referred to as ‘rapid discharges’ (Allen et al., 1992; Alarcon et al., 1995; Wendling et al., 2003). Rapid discharges have been long recognized to be one of the most characteristic patterns of the EZ in focal epilepsy (Bancaud et al., 1965). The surgical prognosis has also been found to be related to the removal of regions with rapid discharges (Alarcon et al., 1995). The second parameter is the delay of involvement of the structure with respect to the onset of the seizure. Indeed, it is generally accepted that the earlier the appearance of a rapid discharge in a given brain area, the more epileptogenic this area. Therefore, both the spectral content and the delay of appearance of the fast ictal activity appear as crucial parameters for determining the EZ. However, no attempt to quantify the combination of these two phenomena (appearance of high-frequency oscillations and latency with respect to seizure onset time) has been made. Consequently, there exists no strict quantitative criterion to define the EZ. In the present study, we propose a new approach to quantify the ‘epileptogenicity’ of recorded brain structures from on the analysis of intracerebral EEG signals. This approach is based on an ‘Epileptogenicity Index’ (EI) that combines both spectral and temporal parameters, respectively related to the propensity of a brain area to generate rapid discharges and to the time for this area to become involved into the seizure process. We chose to first develop and validate this approach in the context of mesial temporal lobe epilepsies (MTLE), considered to be a well-known model of ‘multistructural’ epileptogenic zone (Bragin et al., 2000; Bartolomei et al., 2004b). Indeed, it is quite usual that distinct structures of the mesial part of the temporal lobe are conjointly involved at the beginning of seizures. The participation of the hippocampus, as well as that of the amygdala to a lesser extent, has been reporte (...truncated)