Involvement of the contralateral hippocampus in ictal-like but not interictal epileptic activities in the kainate mouse model of temporal lobe epilepsy.

OBJECTIVE: Animal and human studies have shown that the seizure-generating region is vastly dependent on distant neuronal hubs that can decrease duration and propagation of ongoing seizures. However, we still lack a comprehensive understanding of the impact of distant brain areas on specific interictal and ictal epileptic activities (e.g., isolated spikes, spike trains, seizures). Such knowledge is critically needed, because all kinds of epileptic activities are not equivalent in terms of clinical expression and impact on the progression of the disease. METHODS: We used surface high-density electroencephalography and multisite intracortical recordings, combined with pharmacological silencing of specific brain regions in the well-known kainate mouse model of temporal lobe epilepsy. We tested the impact of selective regional silencing on the generation of epileptic activities within a continuum ranging from very transient to more sustained and long-lasting discharges reminiscent of seizures. RESULTS: Silencing the contralateral hippocampus completely suppresses sustained ictal activities in the focus, as efficiently as silencing the focus itself, but whereas focus silencing abolishes all focus activities, contralateral silencing fails to control transient spikes. In parallel, we observed that sustained focus epileptiform discharges in the focus are preceded by contralateral firing and more strongly phase-locked to bihippocampal delta/theta oscillations than transient spiking activities, reinforcing the presumed dominant role of the contralateral hippocampus in promoting long-lasting, but not transient, epileptic activities. SIGNIFICANCE: Altogether, our work provides suggestive evidence that the contralateral hippocampus is necessary for the interictal to ictal state transition and proposes that crosstalk between contralateral neuronal activity and ipsilateral delta/theta oscillation could be a candidate mechanism underlying the progression from short- to long-lasting epileptic activities.

Extracting the Invisible: Mesial Temporal Source Detection in Simultaneous EEG and SEEG Recordings.

Epileptic source detection relies mainly on visual expertise of scalp EEG signals, but it is recognised that epileptic discharges can escape to this expertise due to a deep localization of the brain sources that induce a very low, even negative, signal to noise ratio. In this methodological study, we aimed to investigate the feasibility of extracting deep mesial temporal sources that were invisible in scalp EEG signals using blind source separation (BSS) methods (infomax ICA, extended infomax ICA, and JADE) combined with a statistical measure (kurtosis). We estimated the effect of different methodological and physiological parameters that could alter or improve the extraction. Using nine well-defined mesial epileptic networks (1949 spikes) obtained from seven patients and simultaneous EEG-SEEG recordings, the first independent component extracted from the scalp EEG signals was validated in mean from 46 to 80% according to the different parameters. The three BSS methods equally performed (no significant difference) and no influence of the number of scalp electrodes used was found. At the opposite, the number and amplitude of spikes included in the averaging before the extraction modified the performance. Anyway, despite their invisibility in scalp EEG signals, this study demonstrates that deep source extraction is feasible under certain conditions and with the use of common signal analysis toolboxes. This finding confirms the crucial need to continue the signal analysis of scalp EEG recordings which contains subcortical signals that escape to expert visual analysis but could be found by signal processing.

Extent of Single-Neuron Activity Modulation by Hippocampal Interictal Discharges Predicts Declarative Memory Disruption in Humans.

Memory deficits are common in epilepsy patients. In these patients, the interictal EEG commonly shows interictal epileptiform discharges (IEDs). While IEDs are associated with transient cognitive impairments, it remains poorly understood why this is. We investigated the effects of human (male and female) hippocampal IEDs on single-neuron activity during a memory task in patients with medically refractory epilepsy undergoing depth electrode monitoring. We quantified the effects of hippocampal IEDs on single-neuron activity and the impact of this modulation on subjectively declared memory strength. Across all recorded neurons, the activity of 50 of 728 neurons were significantly modulated by IEDs, with the strongest modulation in the medial temporal lobe (33 of 416) and in particular the right hippocampus (12 of 58). Putative inhibitory neurons, as identified by their extracellular signature, were more likely to be modulated by IEDs than putative excitatory neurons (19 of 157 vs 31 of 571). Behaviorally, the occurrence of hippocampal IEDs was accompanied by a disruption of recognition of familiar images only if they occurred up to 2 s before stimulus onset. In contrast, IEDs did not impair encoding or recognition of novel images, indicating high temporal and task specificity of the effects of IEDs. The degree of modulation of individual neurons by an IED correlated with the declared confidence of a retrieval trial, with higher firing rates indicative of reduced confidence. Together, these data link the transient modulation of individual neurons by IEDs to specific declarative memory deficits in specific cell types, thereby revealing a mechanism by which IEDs disrupt medial temporal lobe-dependent declarative memory retrieval processes.SIGNIFICANCE STATEMENT Interictal epileptiform discharges (IEDs) are thought to be a cause of memory deficits in chronic epilepsy patients, but the underlying mechanisms are not understood. Utilizing single-neuron recordings in epilepsy patients, we found that hippocampal IEDs transiently change firing of hippocampal neurons and disrupted selectively the retrieval, but not encoding, of declarative memories. The extent of the modulation of the individual firing of hippocampal neurons by an IED predicted the extent of reduction of subjective retrieval confidence. Together, these data reveal a specific kind of transient cognitive impairment caused by IEDs and link this impairment to the modulation of the activity of individual neurons. Understanding the mechanisms by which IEDs impact memory is critical for understanding memory impairments in epilepsy patients.

Slow oscillations open susceptible time windows for epileptic discharges.

OBJECTIVE: In patients with epilepsy, interictal epileptic discharges are a diagnostic hallmark of epilepsy and represent abnormal, so-called "irritative" activity that disrupts normal cognitive functions. Despite their clinical relevance, their mechanisms of generation remain poorly understood. It is assumed that brain activity switches abruptly, unpredictably, and supposedly randomly to these epileptic transients. We aim to study the period preceding these epileptic discharges, to extract potential proepileptogenic mechanisms supporting their expression. METHODS: We used multisite intracortical recordings from patients who underwent intracranial monitoring for refractory epilepsy, the majority of whom had a mesial temporal lobe seizure onset zone. Our objective was to evaluate the existence of proepileptogenic windows before interictal epileptic discharges. We tested whether the amplitude and phase synchronization of slow oscillations (.5-4 Hz and 4-7 Hz) increase before epileptic discharges and whether the latter are phase-locked to slow oscillations. Then, we tested whether the phase-locking of neuronal activity (assessed by high-gamma activity, 60-160 Hz) to slow oscillations increases before epileptic discharges to provide a potential mechanism linking slow oscillations to interictal activities. RESULTS: Changes in widespread slow oscillations anticipate upcoming epileptic discharges. The network extends beyond the irritative zone, but the increase in amplitude and phase synchronization is rather specific to the irritative zone. In contrast, epileptic discharges are phase-locked to widespread slow oscillations and the degree of phase-locking tends to be higher outside the irritative zone. Then, within the irritative zone only, we observe an increased coupling between slow oscillations and neuronal discharges before epileptic discharges. SIGNIFICANCE: Our results show that epileptic discharges occur during vulnerable time windows set up by a specific phase of slow oscillations. The specificity of these permissive windows is further reinforced by the increased coupling of neuronal activity to slow oscillations. These findings contribute to our understanding of epilepsy as a distributed oscillopathy and open avenues for future neuromodulation strategies aiming at disrupting proepileptic mechanisms.

Electrophysiological Evidence for the Development of a Self-Sustained Large-Scale Epileptic Network in the Kainate Mouse Model of Temporal Lobe Epilepsy.

Most research on focal epilepsy focuses on mechanisms of seizure generation in the primary epileptic focus (EF). However, neurological deficits that are not directly linked to seizure activity and that may persist after focus removal are frequent. The recruitment of remote brain regions of an epileptic network (EN) is recognized as a possible cause, but a profound lack of experimental evidence exists concerning their recruitment and the type of pathological activities they exhibit. We studied the development of epileptic activities at the large-scale in male mice of the kainate model of unilateral temporal lobe epilepsy using high-density surface EEG and multiple-site intracortical recordings. We show that, along with focal spikes and fast ripples that remain localized to the injected hippocampus (i.e., the EF), a subpopulation of spikes that propagate across the brain progressively emerges even before the expression of seizures. The spatiotemporal propagation of these generalized spikes (GSs) is highly stable within and across animals, defining a large-scale EN comprising both hippocampal regions and frontal cortices. Interestingly, GSs are often concomitant with muscular twitches. In addition, while fast ripples are, as expected, highly frequent in the EF, they also emerge in remote cortical regions and in particular in frontal regions where GSs propagate. Finally, we demonstrate that these remote interictal activities are dependent on the focus in the early phase of the disease but continue to be expressed after focus silencing at later stages. Our results provide evidence that neuronal networks outside the initial focus are progressively altered during epileptogenesis.SIGNIFICANCE STATEMENT It has long been held that the epileptic focus is responsible for triggering seizures and driving interictal activities. However, focal epilepsies are associated with heterogeneous symptoms, calling into question the concept of a strictly focal disease. Using the mouse model of hippocampal sclerosis, this work demonstrates that focal epilepsy leads to the development of pathological activities specific to the epileptic condition, notably fast ripples, that appear outside of the primary epileptic focus. Whereas these activities are dependent on the focus early in the disease, focus silencing fails to control them in the chronic stage. Thus, dynamical changes specific to the epileptic condition are built up outside of the epileptic focus along with disease progression, which provides supporting evidence for network alterations in focal epilepsy.

Epilepsy and interictal epileptiform activity in patients with autism spectrum disorders.

PURPOSE: The purpose of this study was to determine the prevalence of epilepsy and subclinical epileptiform abnormalities in children with autism spectrum disorder (ASD), and to investigate its effects on core autistic symptoms and adaptive behavior skills. METHODS: Patients with diagnosis of ASD who met full criteria on Autism Diagnostic Interview-Revised (ADI-R) were included in the study. Adaptive behavior skills were assessed by Vineland Adaptive Behavior Scale-II (VABS-II). Clinical assessment for epilepsy and video electroencephalography (EEG) (v-EEG) examinations during wakefulness and/or sleep were prospectively performed in all patients. RESULTS: A total of 112 patients with diagnosis of ASD of mean age 6.58 ±â€¯3.72 were included in the study. Based on clinical and v-EEG assessments, three groups of patients were defined: 1) patients with epilepsy (n = 17; 15.2%); 2) patients with epileptiform discharges in absence of clinical seizures (n = 14; 12.5%); 3) patients without epilepsy and without epileptiform discharges (n = 81; 72.3%). There were no significant differences between three groups of patients on ADI-R subscores. Speech development was also not significantly related to epilepsy. There was a slight tendency of the VABS-II motor skills score to be higher in the group of patients with autism without clinical diagnosis of epilepsy and without subclinical epileptiform discharges (p < 0.05) in comparison with the two other groups. According to this tendency, we might claim that patients with higher scores on motor skills could have 0.88 times lower odds for having epileptiform EEG activity. CONCLUSIONS: According to our results, we were not able to detect differences in the ADI-R between the three populations with ASD, all with unknown etiology. Epilepsy, as well as subclinical epileptic discharges, showed small effects on Motor Skills in patients with autism, and had no effect on adaptive behavior Communication/Socialization/Daily Living Skills.

Electroencephalogram (EEG) for children with autism spectrum disorder: evidential considerations for routine screening.

Routine electroencephalograms (EEG) are not recommended as a screen for epileptic discharges (EDs) in current practice guidelines for children with autism spectrum disorder (ASD). However, a review of the research from the last three decades suggests that this practice should be reevaluated. The significant comorbidity between epilepsy and ASD, its shared biological pathways, risk for developmental regression, and cognitive challenges demand increased clinical investigation requiring a proactive approach. This review highlights and explains the need for screening EEGs for children with ASD. EEG would assist in differentiating EDs from core features of ASD and could be included in a comprehensive assessment. EEG also meets the demand for evidence-based precision medicine and focused care for the individual, especially when overlapping processes of development are present.

Electroencephalogram findings in patients with posterior cortical atrophy.

AIM OF THE STUDY: The aim of this study is to evaluate standard scalp EEG findings in patients with posterior cortical atrophy (PCA), an atypical variant of Alzheimer's disease (AD). CLINICAL RATIONALE: PCA is a topographically selective variant of AD. Patients with typical AD have an increased likelihood of seizures, which may negatively impact overall functional performance and cognition. It is currently unknown what the typical EEG findings are for patients with PCA. MATERIALS AND METHODS: A retrospective chart review was performed on patients identified either with autopsy confirmed (n=13) or clinically (n=126) as PCA. RESULTS: 139 patients were included though only 23 (16.5%) had undergone EEG recording. The EEG was normal in 6 (26%), while an abnormal EEG was present in 17 (74%). Interictal epileptic discharges (IEDs) were found in 2 of the 23 patients (9%). CONCLUSIONS: This study of limited sample size suggests that there may be an increased predilection to find IEDs within PCA when compared to typical AD. Larger cohorts are required to determine frequency of abnormal EEGs in PCA, roles of AEDs in therapy, and in the selection of preferred AED. CLINICAL IMPLICATIONS: Patients with PCA would potentially benefit from an EEG for assessment of IEDs which may provide the clinician with a therapeutic opportunity.

A Mesiotemporal Lobe Epilepsy Mouse Model.

Among the different forms of epilepsies, mesiotemporal lobe epilepsy (MTLE) is one of the most common and represents the main pharmaco-resistant form of epilepsy. There is therefore an urgent need to better understand this form of epilepsy to develop better anti-epileptic drugs. Many rodent models are mimicking some aspects of the human temporal lobe epilepsy but only few are addressing most of the human mesiotemporal lobe epilepsy. In this article, we describe the main characteristics of a mouse of model of mesial temporal lobe epilepsy. This model is generated by a single injection of kainic acid into the dorsal hippocampus which reproduces most of the morphological and electrophysiological features of human MTLE in a mouse. This model may help to better understand mesial temporal lobe epilepsy and the development of new therapeutic drugs.

Complex patterns of spatially extended generators of epileptic activity: Comparison of source localization methods cMEM and 4-ExSo-MUSIC on high resolution EEG and MEG data.

Electric Source Imaging (ESI) and Magnetic Source Imaging (MSI) of EEG and MEG signals are widely used to determine the origin of interictal epileptic discharges during the pre-surgical evaluation of patients with epilepsy. Epileptic discharges are detectable on EEG/MEG scalp recordings only when associated with a spatially extended cortical generator of several square centimeters, therefore it is essential to assess the ability of source localization methods to recover such spatial extent. In this study we evaluated two source localization methods that have been developed for localizing spatially extended sources using EEG/MEG data: coherent Maximum Entropy on the Mean (cMEM) and 4th order Extended Source Multiple Signal Classification (4-ExSo-MUSIC). In order to propose a fair comparison of the performances of the two methods in MEG versus EEG, this study considered realistic simulations of simultaneous EEG/MEG acquisitions taking into account an equivalent number of channels in EEG (257 electrodes) and MEG (275 sensors), involving a biophysical computational neural mass model of neuronal discharges and realistically shaped head models. cMEM and 4-ExSo-MUSIC were evaluated for their sensitivity to localize complex patterns of epileptic discharges which includes (a) different locations and spatial extents of multiple synchronous sources, and (b) propagation patterns exhibited by epileptic discharges. Performance of the source localization methods was assessed using a detection accuracy index (Area Under receiver operating characteristic Curve, AUC) and a Spatial Dispersion (SD) metric. Finally, we also presented two examples illustrating the performance of cMEM and 4-ExSo-MUSIC on clinical data recorded using high resolution EEG and MEG. When simulating single sources at different locations, both 4-ExSo-MUSIC and cMEM exhibited excellent performance (median AUC significantly larger than 0.8 for EEG and MEG), whereas, only for EEG, 4-ExSo-MUSIC showed significantly larger AUC values than cMEM. On the other hand, cMEM showed significantly lower SD values than 4-ExSo-MUSIC for both EEG and MEG. When assessing the impact of the source spatial extent, both methods provided consistent and reliable detection accuracy for a wide range of source spatial extents (source sizes ranging from 3 to 20cm2 for MEG and 3 to 30cm2 for EEG). For both EEG and MEG, 4-ExSo-MUSIC localized single source of large signal-to-noise ratio better than cMEM. In the presence of two synchronous sources, cMEM was able to distinguish well the two sources (their location and spatial extent), while 4-ExSo-MUSIC only retrieved one of them. cMEM was able to detect the spatio-temporal propagation patterns of two synchronous activities while 4-ExSo-MUSIC favored the strongest source activity. Overall, in the context of localizing sources of epileptic discharges from EEG and MEG data, 4-ExSo-MUSIC and cMEM were found accurately sensitive to the location and spatial extent of the sources, with some complementarities. Therefore, they are both eligible for application on clinical data.

Comparing cortical auditory processing in children with typical and atypical benign epilepsy with centrotemporal spikes: Electrophysiologic evidence of the role of non-rapid eye movement sleep abnormalities.

OBJECTIVE: The mismatch negativity (MMN) is an objective measure of central auditory discrimination. MMN alterations have been shown in children with language and/or developmental disorders. In benign focal epilepsies, neuropsychological disorders are often reported and linked to interictal epileptic discharges (IEDs) during non-rapid eye movement (NREM) sleep. There are few studies reporting MMN in children with benign epilepsy with centrotemporal spikes (BECTS) and sleep IEDs. Moreover, no MMN recording has yet been reported in atypical BECTS children with continuous spike-and-wave during sleep (CSWS). We retrospectively compared MMN in typical and atypical BECTS children, particularly addressing the impact of NREM sleep IEDs on auditory discrimination. Moreover, we attempted a neuropsychological characterization of patients. METHODS: The MMN was recorded in 9 normal controls and 23 patients (14 typical BECTS and 9 atypical BECTS) in an oddball paradigm with syllable stimuli. MMN, sleep electroencephalography (EEG) and neuropsychological evaluation were realized in the same testing session. RESULTS: Measurable MMN responses to speech stimuli were identified in both the control and patient groups. A significant difference between control and atypical BECTS children was found with respect to amplitude (p = 0.0061). Atypical BECTS also showed a lower MMN amplitude with respect to typical BECTS, but this difference did not reach statistical significance (p = 0.0545). Statistical comparisons between groups revealed no differences in latency. Among the neuropsychological variables, academic difficulties were significantly more prominent in the patients with atypical BECTS (p = 0.04). SIGNIFICANCE: CSWS EEG pattern affects auditory discrimination and may have a long-lasting impact on academic skills acquisition, whereas in typical BECTS children with a lower degree of IED NREM sleep, plastic brain reorganization or the preservation of participating networks may prevent such difficulty. Early electrophysiologic identification of auditory discrimination deficits in epileptic children could be used in early rehabilitation, thereby reducing the risk of developing neuropsychological disorders.

MEG-EEG Information Fusion and Electromagnetic Source Imaging: From Theory to Clinical Application in Epilepsy.

The purpose of this study is to develop and quantitatively assess whether fusion of EEG and MEG (MEEG) data within the maximum entropy on the mean (MEM) framework increases the spatial accuracy of source localization, by yielding better recovery of the spatial extent and propagation pathway of the underlying generators of inter-ictal epileptic discharges (IEDs). The key element in this study is the integration of the complementary information from EEG and MEG data within the MEM framework. MEEG was compared with EEG and MEG when localizing single transient IEDs. The fusion approach was evaluated using realistic simulation models involving one or two spatially extended sources mimicking propagation patterns of IEDs. We also assessed the impact of the number of EEG electrodes required for an efficient EEG-MEG fusion. MEM was compared with minimum norm estimate, dynamic statistical parametric mapping, and standardized low-resolution electromagnetic tomography. The fusion approach was finally assessed on real epileptic data recorded from two patients showing IEDs simultaneously in EEG and MEG. Overall the localization of MEEG data using MEM provided better recovery of the source spatial extent, more sensitivity to the source depth and more accurate detection of the onset and propagation of IEDs than EEG or MEG alone. MEM was more accurate than the other methods. MEEG proved more robust than EEG and MEG for single IED localization in low signal-to-noise ratio conditions. We also showed that only few EEG electrodes are required to bring additional relevant information to MEG during MEM fusion.

The role of extracellular glutamate homeostasis dysregulated by astrocyte in epileptic discharges: a model evidence.

Glutamate (Glu) is a predominant excitatory neurotransmitter that acts on glutamate receptors to transfer signals in the central nervous system. Abnormally elevated extracellular glutamate levels is closely related to the generation and transition of epileptic seizures. However, there lacks of investigation regarding the role of extracellular glutamate homeostasis dysregulated by astrocyte in neuronal epileptic discharges. According to this, we propose a novel neuron-astrocyte computational model (NAG) by incorporating extracellular Glu concentration dynamics from three aspects of regulatory mechanisms: (1) the Glu uptake through astrocyte EAAT2; (2) the binding and release Glu via activating astrocyte mGluRs; and (3) the Glu free diffusion in the extracellular space. Then the proposed model NAG is analyzed theoretically and numerically to verify the effect of extracellular Glu homeostasis dysregulated by such three regulatory mechanisms on neuronal epileptic discharges. Our results demonstrate that the neuronal epileptic discharges can be aggravated by the downregulation expression of EAAT2, the aberrant activation of mGluRs, and the elevated Glu levels in extracellular micro-environment; as well as various discharge states (including bursting, mixed-mode spiking, and tonic firing) can be transited by their combination. Furthermore, we find that such factors can also alter the bifurcation threshold for the generation and transition of epileptic discharges. The results in this paper can be helpful for researchers to understand the astrocyte role in modulating extracellular Glu homeostasis, and provide theoretical basis for future related experimental studies.

Striatum- and Cerebellum-Modulated Epileptic Networks Varying Across States with and without Interictal Epileptic Discharges.

Idiopathic generalized epilepsy (IGE) is characterized by cryptogenic etiology and the striatum and cerebellum are recognized as modulators of epileptic network. We collected simultaneous electroencephalogram and functional magnetic resonance imaging data from 145 patients with IGE, 34 of whom recorded interictal epileptic discharges (IEDs) during scanning. In states without IEDs, hierarchical connectivity was performed to search core cortical regions which might be potentially modulated by striatum and cerebellum. Node-node and edge-edge moderation models were constructed to depict direct and indirect moderation effects in states with and without IEDs. Patients showed increased hierarchical connectivity with sensorimotor cortices (SMC) and decreased connectivity with regions in the default mode network (DMN). In the state without IEDs, striatum, cerebellum, and thalamus were linked to weaken the interactions of regions in the salience network (SN) with DMN and SMC. In periods with IEDs, overall increased moderation effects on the interaction between regions in SN and DMN, and between regions in DMN and SMC were observed. The thalamus and striatum were implicated in weakening interactions between regions in SN and SMC. The striatum and cerebellum moderated the cortical interaction among DMN, SN, and SMC in alliance with the thalamus, contributing to the dysfunction in states with and without IEDs in IGE. The current work revealed state-specific modulation effects of striatum and cerebellum on thalamocortical circuits and uncovered the potential core cortical targets which might contribute to develop new clinical neuromodulation techniques.

Subclinical epileptiform activity in the Alzheimer continuum: association with disease, cognition and detection method.

BACKGROUND: Epileptic seizures are an established comorbidity of Alzheimer's disease (AD). Subclinical epileptiform activity (SEA) as detected by 24-h electroencephalography (EEG) or magneto-encephalography (MEG) has been reported in temporal regions of clinically diagnosed AD patients. Although epileptic activity in AD probably arises in the mesial temporal lobe, electrical activity within this region might not propagate to EEG scalp electrodes and could remain undetected by standard EEG. However, SEA might lead to faster cognitive decline in AD. AIMS: 1. To estimate the prevalence of SEA and interictal epileptic discharges (IEDs) in a well-defined cohort of participants belonging to the AD continuum, including preclinical AD subjects, as compared with cognitively healthy controls. 2. To evaluate whether long-term-EEG (LTM-EEG), high-density-EEG (hd-EEG) or MEG is superior to detect SEA in AD. 3. To characterise AD patients with SEA based on clinical, neuropsychological and neuroimaging parameters. METHODS: Subjects (n = 49) belonging to the AD continuum were diagnosed according to the 2011 NIA-AA research criteria, with a high likelihood of underlying AD pathophysiology. Healthy volunteers (n = 24) scored normal on neuropsychological testing and were amyloid negative. None of the participants experienced a seizure before. Subjects underwent LTM-EEG and/or 50-min MEG and/or 50-min hd-EEG to detect IEDs. RESULTS: We found an increased prevalence of SEA in AD subjects (31%) as compared to controls (8%) (p = 0.041; Fisher's exact test), with increasing prevalence over the disease course (50% in dementia, 27% in MCI and 25% in preclinical AD). Although MEG (25%) did not withhold a higher prevalence of SEA in AD as compared to LTM-EEG (19%) and hd-EEG (19%), MEG was significantly superior to detect spikes per 50 min (p = 0.002; Kruskall-Wallis test). AD patients with SEA scored worse on the RBANS visuospatial and attention subset (p = 0.009 and p = 0.05, respectively; Mann-Whitney U test) and had higher left frontal, (left) temporal and (left and right) entorhinal cortex volumes than those without. CONCLUSION: We confirmed that SEA is increased in the AD continuum as compared to controls, with increasing prevalence with AD disease stage. In AD patients, SEA is associated with more severe visuospatial and attention deficits and with increased left frontal, (left) temporal and entorhinal cortex volumes. TRIAL REGISTRATION: Clinicaltrials.gov, NCT04131491. 12/02/2020.

Helium Optically Pumped Magnetometers Can Detect Epileptic Abnormalities as Well as SQUIDs as Shown by Intracerebral Recordings.

Magnetoencephalography based on superconducting quantum interference devices (SQUIDs) has been shown to improve the diagnosis and surgical treatment decision for presurgical evaluation of drug-resistant epilepsy. Still, its use remains limited because of several constraints such as cost, fixed helmet size, and the obligation of immobility. A new generation of sensors, optically pumped magnetometers (OPMs), could overcome these limitations. In this study, we validate the ability of helium-based OPM (4He-OPM) sensors to record epileptic brain activity thanks to simultaneous recordings with intracerebral EEG [stereotactic EEG (SEEG)]. We recorded simultaneous SQUIDs-SEEG and 4He-OPM-SEEG signals in one patient during two sessions. We show that epileptic activities on intracerebral EEG can be recorded by OPMs with a better signal-to noise ratio than classical SQUIDs. The OPM sensors open new venues for the widespread application of magnetoencephalography in the management of epilepsy and other neurologic diseases and fundamental neuroscience.

Assessing 72 h vs. 24 h of long-term video-EEG monitoring to confirm the diagnosis of epilepsy: a retrospective observational study.

Introduction: Paroxysmal seizure-like events can be a diagnostic challenge. Inpatient video-electroencephalography (EEG) monitoring (VEM) can be a valuable diagnostic tool, but recommendations for the minimal duration of VEM to confirm or rule out epilepsy are inconsistent. In this study, we aim to determine whether VEM of 48 or 72 h was superior to 24 h. Methods: In this monocentric, retrospective study, we included 111 patients with paroxysmal, seizure-like events who underwent at least 72 h of VEM. Inclusion criteria were as follows: (1) Preliminary workup was inconclusive; (2) VEM admission occurred to confirm a diagnosis; (3) At discharge, the diagnosis of epilepsy was conclusively established. We analyzed the VEM recordings to determine the exact time point of the first occurrence of epileptic abnormalities (EAs; defined as interictal epileptiform discharges or electrographic seizures). Subgroup analyses were performed for epilepsy types and treatment status. Results: In our study population, 69.4% (77/111) of patients displayed EAs during VEM. In this group, the first occurrence of EAs was observed within 24 h in 92.2% (71/77) of patients and within 24-72 h in 7.8% (6/77). There was no statistically significant difference in the incidence of EA between medicated and non-medicated patients or between focal, generalized epilepsies and epilepsies of unknown type. Of the 19 recorded spontaneous electroclinical seizures, 6 (31.6%) occurred after 24 h. Discussion: A VEM of 24 h may be sufficient in the diagnostic workup of paroxysmal seizure-like events under most circumstances. Considering the few cases of first EA in the timeframe between 24 and 72 h, a prolonged VEM may be useful in cases with a high probability of epilepsy or where other strategies like sleep-EEG or ambulatory EEG show inconclusive results. Prolonged VEM increases the chance of recording spontaneous seizures. Our study also highlights a high share of subjects with epilepsy that do not exhibit EAs during 72 h of VEM.

EMHapp: a pipeline for the automatic detection, localization and visualization of epileptic magnetoencephalographic high-frequency oscillations.

Objective.High-frequency oscillations (HFOs) are promising biomarkers for localizing epileptogenic brain tissue. Previous studies have revealed that HFOs that present concurrence with interictal epileptic discharges (IEDs) better delineate epileptogenic brain tissue, particularly for epilepsy patients with multitype interictal discharges. However, the analysis of noninvasively recorded epileptic HFOs involves many complex procedures, such as data preprocessing, detection and source localization, impeding the translation of this approach to clinical practice.Approach.To address these problems, we developed a graphical user interface (GUI)-based pipeline called EMHapp, which can be used for the automatic detection, source localization and visualization of HFO events concurring with IEDs in magnetoencephalography (MEG) signals by using a beamformer-based virtual sensor (VS) technique. An improved VS reconstruction method was developed to enhance the amplitudes of both HFO and IED VS signals. To test the capability of our pipeline, we collected MEG data from 11 complex focal epilepsy patients with surgical resections or seizure onset zones (SOZs) that were identified by intracranial electroencephalography.Main results.Our results showed that the HFO sources of eight patients were concordant with their resection margins or SOZs. Our proposed VS signal reconstruction approach achieved an 83.2% improvement regarding the number of detected HFO events and a 17.3% improvement in terms of the spatial overlaps between the HFO sources and the resection margins or SOZs in comparison with conventional VS reconstruction approaches.Significance.EMHapp is the first GUI-based pipeline for the analysis of epileptic magnetoencephalographic HFOs, which conveniently obtains HFO source locations using clinical data and enables direct translation to clinical applications.

Overview of intraoperative neuromonitoring.

Intraoperative neuromonitoring (IONM) is used widely to reduce neurologic adverse postoperative outcomes. A variety of techniques are used. Initial techniques were used as far back as the 1930s, and the variety of methods expanded greatly since the 1980s. Many methods monitor baseline findings over time. Other methods test for neurologic function to identify nerves or eloquent cortex. Physicians trained in neurophysiology are key for interpretation of findings, supervision of staff, and making medical recommendations to the surgeon or anesthesiologist. Some neurophysiologists provide the services personally, and in other circumstances well-trained technologist staff help with the techniques. Much IONM is provided by the neurophysiology physician in the operating room, whereas in other cases, the physician may be on-line in real time from a remote site. When monitoring identifies changes, the IONM team must give a clear, timely, and compelling message to the surgeon and anesthesiologist.

Vagus nerve stimulation for refractory posttraumatic epilepsy: Efficacy and predictors of seizure outcome.

Background: Traumatic brain injury (TBI) has been recognized as an important and common cause of epilepsy since antiquity. Posttraumatic epilepsy (PTE) is usually associated with drug resistance and poor surgical outcomes, thereby increasing the burden of the illness on patients and their families. Vagus nerve stimulation (VNS) is an adjunctive treatment for medically refractory epilepsy. This study aimed to determine the efficacy of VNS for refractory PTE and to initially evaluate the potential predictors of efficacy. Methods: We retrospectively collected the outcomes of VNS with at least a 1-year follow-up in all patients with refractory PTE. Subgroups were classified as responders and non-responders according to the efficacy of VNS (≥50% or <50% reduction in seizure frequency). Preoperative data were analyzed to screen for potential predictors of VNS efficacy. Results: In total, forty-five patients with refractory PTE who underwent VNS therapy were enrolled. Responders were found in 64.4% of patients, and 15.6% of patients achieved seizure freedom at the last follow-up. In addition, the responder rate increased over time, with 37.8, 44.4, 60, and 67.6% at the 3-, 6-, 12-, and 24-month follow-ups, respectively. After multivariate analysis, generalized interictal epileptic discharges (IEDs) were found to be a negative predictor (OR: 4.861, 95% CI: 1.145-20.632) of VNS efficacy. Conclusion: The results indicated that VNS therapy was effective in refractory PTE patients and was well tolerated over a 1-year follow-up period. Patients with focal or multifocal IEDs were recognized to have better efficacy after VNS therapy.