Fabrice Bartolomei

Epileptic fast activity can be explained by a model of impaired GABAergic dendritic inhibition

This paper focuses on high‐frequency (gamma band) EEG activity, the most characteristic electrophysiological pattern in focal seizures of human epilepsy. It starts with recent hypotheses about: (i) the behaviour of inhibitory interneurons in hippocampal or neocortical networks in the generation of gamma frequency oscillations; (ii) the nonuniform alteration of GABAergic inhibition in experimental epilepsy (reduced dendritic inhibition and increased somatic inhibition); and (iii) the possible depression of GABAA,fast circuit activity by GABAA,slow inhibitory postsynaptic currents. In particular, these hypotheses are introduced in a new computational macroscopic model of EEG activity that includes a physiologically relevant fast inhibitory feedback loop. Results show that strikingly realistic activity is produced by the model when compared to real EEG signals recorded with intracerebral electrodes. They show that, in the model, the transition from interictal to fast ictal activity is explained by the impairment of dendritic inhibition.

International consensus classification of hippocampal sclerosis in temporal lobe epilepsy: A Task Force report from the ILAE Commission on Diagnostic Methods

Hippocampal sclerosis (HS) is the most frequent histopathology encountered in patients with drug‐resistant temporal lobe epilepsy (TLE). Over the past decades, various attempts have been made to classify specific patterns of hippocampal neuronal cell loss and correlate subtypes with postsurgical outcome. However, no international consensus about definitions and terminology has been achieved. A task force reviewed previous classification schemes and proposes a system based on semiquantitative hippocampal cell loss patterns that can be applied in any histopathology laboratory. Interobserver and intraobserver agreement studies reached consensus to classify three types in anatomically well‐preserved hippocampal specimens: HS International League Against Epilepsy (ILAE) type 1 refers always to severe neuronal cell loss and gliosis predominantly in CA1 and CA4 regions, compared to CA1 predominant neuronal cell loss and gliosis (HS ILAE type 2), or CA4 predominant neuronal cell loss and gliosis (HS ILAE type 3). Surgical hippocampus specimens obtained from patients with TLE may also show normal content of neurons with reactive gliosis only (no‐HS). HS ILAE type 1 is more often associated with a history of initial precipitating injuries before age 5 years, with early seizure onset, and favorable postsurgical seizure control. CA1 predominant HS ILAE type 2 and CA4 predominant HS ILAE type 3 have been studied less systematically so far, but some reports point to less favorable outcome, and to differences regarding epilepsy history, including age of seizure onset. The proposed international consensus classification will aid in the characterization of specific clinicopathologic syndromes, and explore variability in imaging and electrophysiology findings, and in postsurgical seizure control.

Relevance of nonlinear lumped-parameter models in the analysis of depth-EEG epileptic signals

Abstract. In the field of epilepsy, the analysis of stereoelectroencephalographic (SEEG, intra-cerebral recording) signals with signal processing methods can help to better identify the epileptogenic zone, the area of the brain responsible for triggering seizures, and to better understand its organization. In order to evaluate these methods and to physiologically interpret the results they provide, we developed a model able to produce EEG signals from “organized” networks of neural populations. Starting from a neurophysiologically relevant model initially proposed by Lopes Da Silva et al. [Lopes da Silva FH, Hoek A, Smith H, Zetterberg LH (1974) Kybernetic 15: 27–37] and recently re-designed by Jansen et al. [Jansen BH, Zouridakis G, Brandt ME (1993) Biol Cybern 68: 275–283] the present study demonstrates that this model can be extended to generate spontaneous EEG signals from multiple coupled neural populations. Model parameters related to excitation, inhibition and coupling are then altered to produce epileptiform EEG signals. Results show that the qualitative behavior of the model is realistic; simulated signals resemble those recorded from different brain structures for both interictal and ictal activities. Possible exploitation of simulations in signal processing is illustrated through one example; statistical couplings between both simulated signals and real SEEG signals are estimated using nonlinear regression. Results are compared and show that, through the model, real SEEG signals can be interpreted with the aid of signal processing methods.

Decreased basal fMRI functional connectivity in epileptogenic networks and contralateral compensatory mechanisms.

A better understanding of interstructure relationship sustaining drug‐resistant epileptogenic networks is crucial for surgical perspective and to better understand the consequences of epileptic processes on cognitive functions. We used resting‐state fMRI to study basal functional connectivity within temporal lobes in medial temporal lobe epilepsy (MTLE) during interictal period. Two hundred consecutive single‐shot GE‐EPI acquisitions were acquired in 37 right‐handed subjects (26 controls, eight patients presenting with left and three patients with right MTLE). For each hemisphere, normalized correlation coefficients were computed between pairs of time‐course signals extracted from five regions involved in MTLE epileptogenic networks (Brodmann area 38, amygdala, entorhinal cortex (EC), anterior hippocampus (AntHip), and posterior hippocampus (PostHip)). In controls, an asymmetry was present with a global higher connectivity in the left temporal lobe. Relative to controls, the left MTLE group showed disruption of the left EC‐AntHip link, and a trend of decreased connectivity of the left AntHip‐PostHip link. In contrast, a trend of increased connectivity of the right AntHip‐PostHip link was observed and was positively correlated to memory performance. At the individual level, seven out of the eight left MTLE patients showed decreased or disrupted functional connectivity. In this group, four patients with left TLE showed increased basal functional connectivity restricted to the right temporal lobe spared by seizures onset. A reverse pattern was observed at the individual level for patients with right TLE. This is the first demonstration of decreased basal functional connectivity within epileptogenic networks with concomitant contralateral increased connectivity possibly reflecting compensatory mechanisms. Hum Brain Mapp 2009.

Gamma Knife Surgery for Epilepsy Related to Hypothalamic Hamartomas

OBJECTIVEDrug-resistant epilepsy associated with hypothalamic hamartomas (HHs) can be cured by microsurgical resection of the lesions. Morbidity and mortality rates for microsurgery in this area are significant. Gamma knife surgery (GKS) is less invasive and seems to be well adapted for this indication. METHODSTo evaluate the safety and efficacy of GKS to treat this uncommon pathological condition, we organized a multicenter retrospective study. Ten patients were treated in seven different centers. The follow-up periods were more than 12 months for eight patients, with a median follow-up period of 28 months (mean, 35 mo; range, 12–71 mo). All patients had severe drug-resistant epilepsy, including frequent gelastic and generalized tonic or tonicoclonic attacks. The median age was 13.5 years (range, 1–32 yr; mean, 14 yr) at the time of GKS. Three patients experienced precocious puberty. All patients had sessile HHs. The median marginal dose was 15.25 Gy (range, 12–20 Gy). Two patients were treated two times (at 19 and 49 mo) because of insufficient efficacy. RESULTSAll patients exhibited improvement. Four patients were seizure-free, one experienced rare nocturnal seizures, one experienced some rare partial seizures but no more generalized attacks, and two exhibited only improvement, with reductions in the frequency of seizures but persistence of some rare generalized seizures. Two patients, now seizure-free, were considered to exhibit insufficient improvement after the first GKS procedure and were treated a second time. A clear correlation between efficacy and dose was observed in this series. The marginal dose was more than 17 Gy for all patients in the successful group and less than 13 Gy for all patients in the “improved” group. No side effects were reported, except for poikilothermia in one patient. Behavior was clearly improved for two patients (with only slight improvements in their epilepsy). Complete coverage of the HHs did not seem to be mandatory, because the dosimetry spared a significant part of the lesions for two patients in the successful group. CONCLUSIONWe report the first series demonstrating that GKS can be a safe and effective treatment for epilepsy related to HHs. We advocate marginal doses greater than or equal to 17 Gy and partial dose-planning when necessary, for avoidance of critical surrounding structures.

Graph theoretical analysis of structural and functional connectivity MRI in normal and pathological brain networks

Graph theoretical analysis of structural and functional connectivity MRI data (ie. diffusion tractography or cortical volume correlation and resting-state or task-related (effective) fMRI, respectively) has provided new measures of human brain organization in vivo. The most striking discovery is that the whole-brain network exhibits “small-world” properties shared with many other complex systems (social, technological, information, biological). This topology allows a high efficiency at different spatial and temporal scale with a very low wiring and energy cost. Its modular organization also allows for a high level of adaptation. In addition, degree distribution of brain networks demonstrates highly connected hubs that are crucial for the whole-network functioning. Many of these hubs have been identified in regions previously defined as belonging to the default-mode network (potentially explaining the high basal metabolism of this network) and the attentional networks. This could explain the crucial role of these hub regions in physiology (task-related fMRI data) as well as in pathophysiology. Indeed, such topological definition provides a reliable framework for predicting behavioral consequences of focal or multifocal lesions such as stroke, tumors or multiple sclerosis. It also brings new insights into a better understanding of pathophysiology of many neurological or psychiatric diseases affecting specific local or global brain networks such as epilepsy, Alzheimer’s disease or schizophrenia. Graph theoretical analysis of connectivity MRI data provides an outstanding framework to merge anatomical and functional data in order to better understand brain pathologies.

Gamma knife surgery in mesial temporal lobe epilepsy: a prospective multicenter study.

Summary:  Purpose: This article is the first prospective documentation of the efficacy and safety of gamma knife surgery (GKS) in the treatment of drug‐resistant epilepsies of mesial temporal lobe origin.

Entorhinal cortex involvement in human mesial temporal lobe epilepsy: an electrophysiologic and volumetric study.

Summary:  Purpose: Several studies have demonstrated diminution in the volume of entorhinal cortex (EC) ipsilateral to the pathologic side in patients with temporal lobe epilepsy (TLE). The relation between the degree of EC atrophy and the epileptogenicity of this structure has never been directly studied. The purpose of the study was to determine whether atrophy of the EC evaluated by the quantitative magnetic resonance imaging (MRI) method is correlated with the epileptogenicity of this structure in TLE.

Familial perisylvian polymicrogyria: a new familial syndrome of cortical maldevelopment

Two familial X‐linked dominant syndromes of cortical maldevelopment have recently been described: double cortex/lissencephaly syndrome and bilateral periventricular nodular heterotopia. We report on 12 kindreds with familial perisylvian polymicrogyria (FPP) presenting at 10 centers, examine the clinical presentation in these familial cases, and propose a possible mode of inheritance. The clinical and radiological pattern was variable among the 42 patients, with clinical differences among the families and even within members of the same family. Pseudobulbar signs, cognitive deficits, epilepsy, and perisylvian abnormalities on imaging studies were not found in all patients. When present, they displayed a spectrum of severity. The only clear correlation in this study was between bilateral imaging findings and abnormal tongue movements and/or pronounced dysarthria. Most of the families provided evidence suggestive of, or compatible with, X‐linked transmission. On the other hand, the pedigrees of 2 families ruled out X‐linked inheritance. The most likely mode of inheritance for these 2 families was autosomal dominant with decreased penetrance; however, autosomal recessive inheritance with pseudodominance could not be ruled out in 1 family. We conclude that FPP appears to be genetically heterogeneous. However, most of the families probably represent a third previously undescribed X‐linked syndrome of cortical maldevelopment. Ann Neurol 2000;48:39–48

Interpretation of interdependencies in epileptic signals using a macroscopic physiological model of the EEG

This paper presents a neurophysiologically relevant model in which vectorial epileptiform electroencephalographic (EEG) signals are produced from multiple coupled neural populations. This model is used to evaluate the performances of non-linear regression analysis as a method to characterize couplings between neural populations from EEG signals they produce. Two quantities, estimated on generated signals, namely the non-linear correlation coefficient and the direction index, are related to the degree and direction of coupling parameters of the model. Their statistical behavior is first studied on a set of signals simulated for relevant configurations of the model. They are then measured on real stereoelectroencephalographic (SEEG) signals. Results obtained in three patients suffering from temporal lobe epilepsy (TLE) show that abnormal functional couplings between cerebral structures, that establish during seizures, can be interpreted in terms of causality. Perspectives are oriented to the identification of epileptogenic networks in TLE.