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Background and Objectives: When seizure onset affects a whole hemisphere, hemispheric disconnections are efficient and safe procedures. However, both lateral peri-insular hemispherotomy and vertical paramedian hemispherotomy approaches report a failure rate around 20%, which can be explained by residual connections giving rise to persistent seizures. In this study, we present the interhemispheric vertical hemispherotomy (IVH), a technical variation of the vertical paramedian hemispherotomy approach, that aims to increase seizure control avoiding residual connections while exposing the corpus callosum., Methods: This is a retrospective study of IVH in two centers, with analysis of clinical and MRI data and outcomes. A detailed description of the technique is provided with a video., Results: IVH was performed in 39 children. The mean age at surgery was 7.2 years, and etiologies were as follows: malformations of cortical development (n = 14), Rasmussen's encephalitis (n = 10), stroke (n = 10), post-traumatic (3), and Sturge-Weber Syndrome (2). Hemispheric disconnection was complete on postoperative MRI in 34 cases. There was no mortality, hydrocephalus occurred in one case, and subdural collection occurred in four cases. A second surgery was performed in four cases because of seizure relapse (n = 3) and/or incomplete disconnection on MRI (n = 4). With a mean follow-up of 3.2 years, International League Against Epilepsy class I epilepsy outcome was obtained for 37/39 patients., Conclusion: IVH is a safe and effective variation of the vertical approaches for hemispheric disconnection. It allows a good exposure and anatomic control of the corpus callosum, which is a frequent site of incomplete disconnection. IVH may be limited by the thalamic volume and the ventricular size, notably in hemimegalencephaly cases., (Copyright © Congress of Neurological Surgeons 2023. All rights reserved.)

Objective: To study longitudinal changes in tuber and whole-brain perfusion in children with tuberous sclerosis complex (TSC) using arterial spin labeling (ASL) perfusion MRI and correlate them with pathological EEG slow wave activity and neurodevelopmental outcomes., Methods: Retrospective longitudinal cohort study of 13 children with TSC, 3 to 6 serial ASL-MRI scans between 2 months and 7 years of age (53 scans in total), and an EEG examination performed within 2 months of the last MRI. Tuber cerebral blood flow (CBF) values were calculated in tuber segmentation masks, and tuber:cortical CBF ratios were used to study tuber perfusion. Logistic regression analysis was performed to identify which initial tuber characteristics (CBF value, volume, location) in the first MRI predicted tubers subsequently associated with EEG slow waves. Whole-brain and lobar CBF values were extracted for all patient scans and age-matched controls. CBF ratios were compared in patients and controls to study longitudinal changes in whole-brain CBF., Results: Perfusion was reduced in tubers associated with EEG slow waves compared with other tubers. Low tuber CBF values around 6 months of age and large tuber volumes were predictive of tubers subsequently associated with EEG slow waves. Patients with severe developmental delay had more severe whole-brain hypoperfusion than those with no/mild delay, which became apparent after 2 years of age and were not associated with a higher tuber load., Conclusions: Dynamic changes in tuber and brain perfusion occur over time. Perfusion is significantly reduced in tubers associated with EEG slow waves. Whole-brain perfusion is significantly reduced in patients with severe delay., Key Points: • Tubers associated with EEG slow wave activity were significantly more hypoperfused than other tubers, especially after 1 year of age. • Larger and more hypoperfused tubers at 6 months of age were more likely to subsequently be associated with pathological EEG slow wave activity. • Patients with severe developmental delay had more extensive and severe global hypoperfusion than those without developmental delay., (© 2022. The Author(s), under exclusive licence to European Society of Radiology.)

Epilepsy presurgical investigation may include focal intracortical single-pulse electrical stimulations with depth electrodes, which induce cortico-cortical evoked potentials at distant sites because of white matter connectivity. Cortico-cortical evoked potentials provide a unique window on functional brain networks because they contain sufficient information to infer dynamical properties of large-scale brain connectivity, such as preferred directionality and propagation latencies.  Here, we developed a biologically informed modelling approach to estimate the neural physiological parameters of brain functional networks from the cortico-cortical evoked potentials recorded in a large multicentric database. Specifically, we considered each cortico-cortical evoked potential as the output of a transient stimulus entering the stimulated region, which directly propagated to the recording region. Both regions were modelled as coupled neural mass models, the parameters of which were estimated from the first cortico-cortical evoked potential component, occurring before 80 ms, using dynamic causal modelling and Bayesian model inversion. This methodology was applied to the data of 780 patients with epilepsy from the F-TRACT database, providing a total of 34 354 bipolar stimulations and 774 445 cortico-cortical evoked potentials. The cortical mapping of the local excitatory and inhibitory synaptic time constants and of the axonal conduction delays between cortical regions was obtained at the population level using anatomy-based averaging procedures, based on the Lausanne2008 and the HCP-MMP1 parcellation schemes, containing 130 and 360 parcels, respectively. To rule out brain maturation effects, a separate analysis was performed for older (>15 years) and younger patients (<15 years). In the group of older subjects, we found that the cortico-cortical axonal conduction delays between parcels were globally short (median = 10.2 ms) and only 16% were larger than 20 ms. This was associated to a median velocity of 3.9 m/s. Although a general lengthening of these delays with the distance between the stimulating and recording contacts was observed across the cortex, some regions were less affected by this rule, such as the insula for which almost all efferent and afferent connections were faster than 10 ms. Synaptic time constants were found to be shorter in the sensorimotor, medial occipital and latero-temporal regions, than in other cortical areas. Finally, we found that axonal conduction delays were significantly larger in the group of subjects younger than 15 years, which corroborates that brain maturation increases the speed of brain dynamics. To our knowledge, this study is the first to provide a local estimation of axonal conduction delays and synaptic time constants across the whole human cortex in vivo, based on intracerebral electrophysiological recordings., (© The Author(s) (2021). Published by Oxford University Press on behalf of the Guarantors of Brain.)

In patients with pharmaco-resistant focal epilepsies investigated with intracranial electroencephalography (iEEG), direct electrical stimulations of a cortical region induce cortico-cortical evoked potentials (CCEP) in distant cerebral cortex, which properties can be used to infer large scale brain connectivity. In 2013, we proposed a new probabilistic functional tractography methodology to study human brain connectivity. We have now been revisiting this method in the F-TRACT project (f-tract.eu) by developing a large multicenter CCEP database of several thousand stimulation runs performed in several hundred patients, and associated processing tools to create a probabilistic atlas of human cortico-cortical connections. Here, we wish to present a snapshot of the methods and data of F-TRACT using a pool of 213 epilepsy patients, all studied by stereo-encephalography with intracerebral depth electrodes. The CCEPs were processed using an automated pipeline with the following consecutive steps: detection of each stimulation run from stimulation artifacts in raw intracranial EEG (iEEG) files, bad channels detection with a machine learning approach, model-based stimulation artifact correction, robust averaging over stimulation pulses. Effective connectivity between the stimulated and recording areas is then inferred from the properties of the first CCEP component, i.e. onset and peak latency, amplitude, duration and integral of the significant part. Finally, group statistics of CCEP features are implemented for each brain parcel explored by iEEG electrodes. The localization (coordinates, white/gray matter relative positioning) of electrode contacts were obtained from imaging data (anatomical MRI or CT scans before and after electrodes implantation). The iEEG contacts were repositioned in different brain parcellations from the segmentation of patients' anatomical MRI or from templates in the MNI coordinate system. The F-TRACT database using the first pool of 213 patients provided connectivity probability values for 95% of possible intrahemispheric and 56% of interhemispheric connections and CCEP features for 78% of intrahemisheric and 14% of interhemispheric connections. In this report, we show some examples of anatomo-functional connectivity matrices, and associated directional maps. We also indicate how CCEP features, especially latencies, are related to spatial distances, and allow estimating the velocity distribution of neuronal signals at a large scale. Finally, we describe the impact on the estimated connectivity of the stimulation charge and of the contact localization according to the white or gray matter. The most relevant maps for the scientific community are available for download on f-tract. eu (David et al., 2017) and will be regularly updated during the following months with the addition of more data in the F-TRACT database. This will provide an unprecedented knowledge on the dynamical properties of large fiber tracts in human., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Focal cortical dysplasia (FCD) is the most common cause of intractable focal epilepsy in children, in whom seizures are most commonly pharmacoresistant from onset. This review summarizes the current understandings of the epidemiology, natural history, and the proposed mechanisms of epileptogenisis in FCD. Advances in neuroimaging techniques have enhanced the recognition of this pathology, which can be subtle. Illustrative neurophysiology and imaging examples are provided to help the clinicians identify diagnostic evidence of suspected FCD. Given the refractory course to pharmacologic management, alternative options such as ketogenic diet, resective surgery or neuromodulation can be considered. Recognition of FCD pathology in children with early onset epilepsy should prompt timely evaluations for resective surgery, which may render a significant number of patients seizure-free and improve neurocognitive outcome., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Epilepsies are characterized by recurrent seizures, which disrupt normal brain function. Alterations in neuronal excitability and excitation-inhibition balance have been shown to promote seizure generation, yet molecular determinants of such alterations remain to be identified. Pannexin channels are nonselective, large-pore channels mediating extracellular exchange of neuroactive molecules. Recent data suggest that these channels are activated under pathological conditions and regulate neuronal excitability. However, whether pannexin channels sustain or counteract chronic epilepsy in human patients remains unknown. We studied the impact of pannexin-1 channel activation in postoperative human tissue samples from patients with epilepsy displaying epileptic activity ex vivo. These samples were obtained from surgical resection of epileptogenic zones in patients suffering from lesional or drug-resistant epilepsy. We found that pannexin-1 channel activation promoted seizure generation and maintenance through adenosine triphosphate signaling via purinergic 2 receptors. Pharmacological inhibition of pannexin-1 channels with probenecid or mefloquine-two medications currently used for treating gout and malaria, respectively-blocked ictal discharges in human cortical brain tissue slices. Genetic deletion of pannexin-1 channels in mice had anticonvulsant effects when the mice were exposed to kainic acid, a model of temporal lobe epilepsy. Our data suggest a proepileptic role of pannexin-1 channels in chronic epilepsy in human patients and that pannexin-1 channel inhibition might represent an alternative therapeutic strategy for treating lesional and drug-resistant epilepsies., (Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Hemispherectomy is a complex multistep procedure with a steep learning curve. Several surgical approaches have been developed, but each requires considerable practice to master. Four experienced pediatric neurosurgeons, who participated in the 2014 Gothenburg Pediatric Epilepsy Surgery Meeting, provided succinct technical summaries of four hemispherectomy approaches: modified functional hemispherectomy, peri-insular hemispherotomy, parasagittal hemispherotomy, and endoscopic-assisted hemispherotomy. No clinical or outcome data are included. Our intention is to reduce the slope and length of the learning curve for surgeons and to improve the understanding of the technical details of hemispherectomy surgery by nonsurgeonmembers of epilepsy teams., (Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.)

Epilepsy, affecting about 1% of the population, comprises a group of neurological disorders characterized by the periodic occurrence of seizures, which disrupt normal brain function. Despite treatment with currently available antiepileptic drugs targeting neuronal functions, one third of patients with epilepsy are pharmacoresistant. In this condition, surgical resection of the brain area generating seizures remains the only alternative treatment. Studying human epileptic tissues has contributed to understand new epileptogenic mechanisms during the last 10 years. Indeed, these tissues generate spontaneous interictal epileptic discharges as well as pharmacologically-induced ictal events which can be recorded with classical electrophysiology techniques. Remarkably, multi-electrode arrays (MEAs), which are microfabricated devices embedding an array of spatially arranged microelectrodes, provide the unique opportunity to simultaneously stimulate and record field potentials, as well as action potentials of multiple neurons from different areas of the tissue. Thus MEAs recordings offer an excellent approach to study the spatio-temporal patterns of spontaneous interictal and evoked seizure-like events and the mechanisms underlying seizure onset and propagation. Here we describe how to prepare human cortical slices from surgically resected tissue and to record with MEAs interictal and ictal-like events ex vivo.

Epilepsy is a paroxysmal condition characterized by repeated transient seizures separated by longer interictal periods. Ictogenesis describes the processes of transition from the interictal state to a seizure. The processes include a preictal state, with specific clinical signs and a distinct electrophysiology which may provide opportunities to anticipate, or even prevent, seizures. Biological mechanisms of ictogenesis remain poorly understood and may vary between conditions/syndromes. We review here ictogenic processes including the involvement of pyramidal cells, interneurons and astrocytes, GABAergic and glutamatergic signaling, and ionic perturbations. Our review suggests that specific excitatory influences at the transition to an ictal event include (1) GABA receptor activation with a neuronal Cl(-) load and (2) a transient increase in external K(+)., (© 2014 Elsevier Inc. All rights reserved.)

Background: In cryptogenic epilepsy or when multifocal seizure onset is suspected, intracranial monitoring of the EEG is required., Objective: To report on the adverse events related to electroencephalogram (EEG) intracranial recording in one of the largest pediatric series published and to discuss the avoidance of adverse events in our experience and with respect to a review of the literature., Methods: A retrospective analysis of our department database and hospital charts of 95 children operated on between 1994 and 2009 was performed., Results: Invasive recording was uneventful in 51.1% of cases. Observed frequency of infection was 14.9%, cerebrospinal fluid leak was 10.6%, brain swelling was 6.4%, and hemorrhage was 17%. Brain swelling was more frequent in older patients, whereas the length of recording, number of electrode contacts used, and presence of depth electrodes were not relevant. Cerebrospinal fluid leakage was completely prevented by the routine introduction of dural graft substitutes in 2003., Conclusion: Invasive recordings carry a noticeable rate of adverse events but provide invaluable information in delineating the epileptogenic zone. The low incidence of such events among younger children suggests that invasive recordings can be successfully performed with low morbidity in this age group.

Background Focal cortical dysplasias (FCD) are a frequent cause of drug-resistant epilepsy in children but are often undetected on structural magnetic resonance imaging (MRI). We aimed to measure and validate the variation of resting state functional MRI (rs-fMRI) blood oxygenation level dependent (BOLD) metrics in surgically proven FCDs in children, to assess the potential yield for detecting and understanding these lesions. Methods We prospectively included pediatric patients with surgically proven FCD with inconclusive structural MRI and healthy controls, who underwent a ten-minute rs-fMRI acquired at 3T. Rs-fMRI data was pre-processed and maps of values of regional homogeneity (ReHo), degree centrality (DC), amplitude of low frequency fluctuations (ALFF) and fractional ALFF (fALFF) were calculated. The variations of BOLD metrics within the to-be-resected areas were analyzed visually, and quantitatively using lateralization indices. BOLD metrics variations were also analyzed in fluorodeoxyglucose-positron emission tomography (FDG-PET) hypometabolic areas. Results We included 7 patients (range: 3–15 years) and 6 aged-matched controls (range: 6–17 years). ReHo lateralization indices were positive in the to-be-resected areas in 4/7 patients, and in 6/7 patients in the additional PET hypometabolic areas. These indices were significantly higher compared to controls in 3/7 and 4/7 patients, respectively. Visual analysis revealed a good spatial correlation between high ReHo areas and MRI structural abnormalities (when present) or PET hypometabolic areas. No consistent variation was seen using DC, ALFF, or fALFF. Conclusion Resting-state fMRI metrics, noticeably increase in ReHo, may have potential to help detect MRI-negative FCDs in combination with other morphological and functional techniques, used in clinical practice and epilepsy-surgery screening. [ABSTRACT FROM AUTHOR]

Epilepsy presurgical investigation may include focal intracortical single-pulse electrical stimulations with depth electrodes, which induce cortico-cortical evoked potentials at distant sites because of white matter connectivity. Cortico-cortical evoked potentials provide a unique window on functional brain networks because they contain sufficient information to infer dynamical properties of large-scale brain connectivity, such as preferred directionality and propagation latencies.  Here, we developed a biologically informed modelling approach to estimate the neural physiological parameters of brain functional networks from the cortico-cortical evoked potentials recorded in a large multicentric database. Specifically, we considered each cortico-cortical evoked potential as the output of a transient stimulus entering the stimulated region, which directly propagated to the recording region. Both regions were modelled as coupled neural mass models, the parameters of which were estimated from the first cortico-cortical evoked potential component, occurring before 80 ms, using dynamic causal modelling and Bayesian model inversion. This methodology was applied to the data of 780 patients with epilepsy from the F-TRACT database, providing a total of 34 354 bipolar stimulations and 774 445 cortico-cortical evoked potentials. The cortical mapping of the local excitatory and inhibitory synaptic time constants and of the axonal conduction delays between cortical regions was obtained at the population level using anatomy-based averaging procedures, based on the Lausanne2008 and the HCP-MMP1 parcellation schemes, containing 130 and 360 parcels, respectively. To rule out brain maturation effects, a separate analysis was performed for older (>15 years) and younger patients (<15 years). In the group of older subjects, we found that the cortico-cortical axonal conduction delays between parcels were globally short (median = 10.2 ms) and only 16% were larger than 20 ms. This was associated to a median velocity of 3.9 m/s. Although a general lengthening of these delays with the distance between the stimulating and recording contacts was observed across the cortex, some regions were less affected by this rule, such as the insula for which almost all efferent and afferent connections were faster than 10 ms. Synaptic time constants were found to be shorter in the sensorimotor, medial occipital and latero-temporal regions, than in other cortical areas. Finally, we found that axonal conduction delays were significantly larger in the group of subjects younger than 15 years, which corroborates that brain maturation increases the speed of brain dynamics. To our knowledge, this study is the first to provide a local estimation of axonal conduction delays and synaptic time constants across the whole human cortex in vivo, based on intracerebral electrophysiological recordings. [ABSTRACT FROM AUTHOR]

Objective: Dysregulation of γ-aminobutyric acidergic (GABAergic) transmission has been reported in lesional acquired epilepsies (gliomas, hippocampal sclerosis). We investigated its involvement in a developmental disorder, human focal cortical dysplasia (FCD), focusing on chloride regulation driving GABAergic signals.Methods: In vitro recordings of 47 human cortical acute slices from 11 pediatric patients who received operations for FCD were performed on multielectrode arrays. GABAergic receptors and chloride regulators were pharmacologically modulated. Immunostaining for chloride cotransporter KCC2 and interneurons were performed on recorded slices to correlate electrophysiology and expression patterns.Results: FCD slices retain intrinsic epileptogenicity. Thirty-six of 47 slices displayed spontaneous interictal discharges, along with a pattern specific to the histological subtypes. Ictal discharges were induced in proepileptic conditions in 6 of 8 slices in the areas generating spontaneous interictal discharges, with a transition to seizure involving the emergence of preictal discharges. Interictal discharges were sustained by GABAergic signaling, as a GABAA receptor blocker stopped them in 2 of 3 slices. Blockade of NKCC1 Cl- cotransporters further controlled interictal discharges in 9 of 12 cases, revealing a Cl- dysregulation affecting actions of GABA. Immunohistochemistry highlighted decreased expression and changes in KCC2 subcellular localization and a decrease in the number of GAD67-positive interneurons in regions generating interictal discharges.Interpretation: Altered chloride cotransporter expression and changes in interneuron density in FCD may lead to paradoxical depolarization of pyramidal cells. Spontaneous interictal discharges are consequently mediated by GABAergic signals, and targeting chloride regulation in neurons may be considered for the development of new antiepileptic drugs. Ann Neurol 2019; 1-14 ANN NEUROL 2019;85:204-217. [ABSTRACT FROM AUTHOR]

In reflex epilepsies, alteration of γ oscillations may mediate transition between interictal and ictal states. Here, we explored a patient having seizures triggered bysyrup intake. From intracranial electroencephalography combined with functional MRI, the overlap of the gustatory cortex and of the preictaland ictal onset zones, as defined by early gamma changes, motivated the successful resective surgery of the middle short gyrus of the right insula. This case provides a rare demonstration from human gamma activity that the route to seizure may be supported by the interplay between physiological and epileptogenic networks. [ABSTRACT FROM AUTHOR]