Studying Network Mechanisms Using Intracranial Stimulation in Epileptic Patients

Patients suffering from focal drug-resistant epilepsy who are explored using intracranial electrodes allow to obtain data of exceptional value for studying brain dynamics in correlation with pathophysiological and cognitive processes. Direct electrical stimulation (DES) of cortical regions and axonal tracts in those patients elicits a number of very specific perceptual or behavioral responses, but also abnormal responses due to specific configurations of epileptic networks. Here, we review how anatomo-functional brain connectivity and epilepsy network mechanisms can be assessed from DES responses measured in patients. After a brief summary of mechanisms of action of brain electrical stimulation, we recall the conceptual framework for interpreting DES results in the context of brain connectivity and review how DES can be used for the characterization of functional networks, the identification of the seizure onset zone, the study of brain plasticity mechanisms, and the anticipation of epileptic seizures. This pool of exceptional data may be underexploited by fundamental research on brain connectivity and leaves much to be learned

: Seizure onset zone imaging

International audienceStereo-electroencephalography is used to localize the seizure onset zone and connected neuronal networks in surgical candidates suffering from intractable focal epilepsy. The concept of an epileptogenicity index has been proposed recently to represent the likelihood of various regions being part of the seizure onset zone. It quantifies low-voltage fast activity, the electrophysiological signature of seizure onset usually assessed visually by neurologists. Here, we revisit epileptogenicity in light of neuroimaging tools such as those provided in statistical parametric mapping software. Our goal is to propose a robust approach, allowing easy exploration of patients' brains in time and space. The procedure is based upon statistical parametric mapping, which is an established framework for comparing multi-dimensional image data that allows one to correct for inherent multiple comparisons. Statistics can also 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 anatomic atlas. Results are obtained from three case studies (insular reflex epilepsy, cryptogenic frontal epilepsy and lesional occipital epilepsy) where tailored resection was performed, and from a group of 10 patients suffering from mesial temporal lobe epilepsy. They illustrate the basics of the technique and demonstrate its very good reproducibility and specificity. Most importantly, the proposed approach to the quantification of the seizure onset zone allows one to summarize complex signals in terms of a time-series of statistical parametric maps that can support clinical decisions. Quantitative neuroimaging of stereo-electroencephalographic features of seizures might thus help to provide better pre-surgical assessment of patients undergoing resective surgery

Agricultural activities and risk of central nervous system tumors among French farm managers: Results from the <scp>TRACTOR</scp> project

International audienceThe etiology of central nervous system (CNS) tumors is complex and involves many suspected risk factors. Scientific evidence remains insufficient, in particular in the agricultural field. The goal of our study was to investigate associations between agricultural activities and CNS tumors in the entire French farm manager workforce using data from the TRACTOR project. The TRACTOR project hold a large administrative health database covering the entire French agricultural workforce, over the period 2002-2016, on the whole French metropolitan territory. Associations were estimated for 26 activities and CNS tumors using Cox proportional hazards model, with time to first CNS tumor insurance declaration as the underlying timescale, adjusting for sex, age and geographical area. There were 1017 cases among 1 036 069 farm managers, including 317 meningiomas and 479 gliomas. Associations varied with tumor types, sex and types of crop and animal farming. Analyses showed several increased risks of CNS tumors, in particular for animal farming. The main increases in risk were observed for meningioma in mixed dairy and cow farming (hazard ratio [HR] = 1.75, 95% confidence interval [CI]: 1.09-2.81) and glioma in pig farming (HR = 2.28, 95% CI: 1.37-3.80). Our study brings new insights on the association of a wide range of agricultural activities and CNS tumor and subtype-specific risks in farm managers. Although these findings need to be corroborated in further studies and should be interpreted cautiously, they could have implications for enhancing CNS tumor surveillance in agriculture

[Presurgical evaluation of intractable epilepsy using stereo-electro-encephalography methodology: principles, technique and morbidity]

International audienceIn the stereo-electro-encephalography (SEEG) methodology developed by Talairach and Bancaud in Sainte-Anne Hospital in Paris, France, the objective of placing depth electrode recordings in presurgical evaluation is to study the spatial and temporal organization of a seizure. This defines for each patient the cortical onset zone, the propagation pattern of the seizure, and the possible involvement of eloquent areas of the cortex. This methodology requires a meticulous stereotactic surgical technique. We report here the SEEG methodology, surgical technique, and morbidity

Cortical stimulation of the epileptogenic zone for the treatment of focal motor seizures: an experimental study in the nonhuman primate.

International audienceBACKGROUND: Cortical stimulation is under investigation in clinical trials of drug-resistant epilepsy. Results are heterogeneous; therefore, more evidence from animal studies is required. OBJECTIVE: To investigate the therapeutic effects of parameters of direct stimulation of the cortical focus in a Macaca fascicularis presenting focal motor epilepsy. METHODS: We developed a model of motor seizures after intracortical injection of penicillin G in the primary motor cortex of a Macaca fascicularis. We performed electric epidural cortical stimulation at low, medium, and high frequency using continuous or short-term stimulation. Short-term stimulation was triggered on seizure onset, either visually or automatically with a seizure detection algorithm connected to a programmable stimulator. RESULTS: Automated detection could detect 100% of the seizures, but ensuing cortical electric stimulation failed to abort seizures. CONCLUSION: This study demonstrates the inefficacy of the stimulation of the cortical focus to prevent seizures induced by local injection of penicillin G. Because this model may be too severe to allow comparison to human epilepsies, further work is required in other monkey models of focal epilepsy

Lifetime of Itrel II pulse generators for subthalamic nucleus stimulation in Parkinson's disease.

International audienceThe efficacy of bilateral subthalamic nucleus (STN) stimulation in Parkinson's disease (PD) is well-established but little is known about the lifetime of implanted pulse generators (IPG). To investigate the lifetime of the bilaterally implanted Itrel II(R) (Medtronic, Minneapolis) pulse generator, the first 49 consecutive patients with PD having been operated on at our center for bilateral STN chronic stimulation were reviewed with noting of the stimulation parameters in use prior to IPG replacement. The mean electrical voltage was 3.2 +/- 0.3 V, mean pulse width was 65 +/- 10 mus, and mean frequency was 145 +/- 16 Hz. Replacement of an IPG was anticipated in 25% due to unilateral low-battery signaling, or end of life. In either case, replacement of the contralateral IPG was undertaken simultaneously. The mean IPG lifetime was 83 +/- 14 [40-113] months. The IPG lifetime correlated with the total electrical energy delivered (P = 0.002, r = -0.496). Unilateral IPG end-of-life generally led to subacute worsening of contralateral parkinsonism. In 25% of patients, there was also a worsening of axial symptoms leading to potential medical emergencies such as falls (10%), aspiration pneumonia (10%), or psychosis (5%). A close monitoring of patients and an anticipation of IPG replacement in the case of a low-battery signal are recommended