ICU-Electroencephalogram Unit Improves Outcome in Status Epilepticus Patients: A Retrospective Before-After Study.

OBJECTIVES: Continuous electroencephalogram (cEEG) monitoring is recommended for status epilepticus (SE) management in ICU but is still underused due to resource limitations and inconclusive evidence regarding its impact on outcome. Furthermore, the term "continuous monitoring" often implies continuous recording with variable intermittent review. The establishment of a dedicated ICU-electroencephalogram unit may fill this gap, allowing cEEG with nearly real-time review and multidisciplinary management collaboration. This study aimed to evaluate the effect of ICU-electroencephalogram unit establishing on SE outcome and management. DESIGN: Single-center retrospective before-after study. SETTING: Neuro-ICU of a Swiss academic tertiary medical care center. PATIENTS: Adult patients treated for nonhypoxic SE between November 1, 2015, and December 31, 2023. INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: Data from all SE patients were assessed, comparing those treated before and after ICU-electroencephalogram unit introduction. Primary outcomes were return to premorbid neurologic function, ICU mortality, SE duration, and ICU SE management. Secondary outcomes were SE type and etiology. Two hundred seven SE patients were included, 149 (72%) before and 58 (38%) after ICU-electroencephalogram unit establishment. ICU-electroencephalogram unit introduction was associated with increased detection of nonconvulsive SE (p = 0.003) and SE due to acute symptomatic etiology (p = 0.019). Regression analysis considering age, comorbidities, SE etiology, and SE semeiology revealed a higher chance of returning to premorbid neurologic function (p = 0.002), reduced SE duration (p = 0.024), and a shift in SE management with increased use of antiseizure medications (p = 0.007) after ICU-electroencephalogram unit introduction. CONCLUSIONS: Integrating neurology expertise in the ICU setting through the establishment of an ICU-electroencephalogram unit with nearly real-time cEEG review, shortened SE duration, and increased likelihood of returning to premorbid neurologic function, with an increased number of antiseizure medications used. Further studies are warranted to validate these findings and assess long-term prognosis.

High-density electroencephalographic functional networks in genetic generalized epilepsy: Preserved whole-brain topology hides local reorganization.

OBJECTIVE: Genetic generalized epilepsy (GGE) accounts for approximately 20% of adult epilepsy cases and is considered a disorder of large brain networks, involving both hemispheres. Most studies have not shown any difference in functional whole-brain network topology when compared to healthy controls. Our objective was to examine whether this preserved global network topology could hide local reorganizations that balance out at the global network level. METHODS: We recorded high-density electroencephalograms from 20 patients and 20 controls, and reconstructed the activity of 118 regions. We computed functional connectivity in windows free of interictal epileptiform discharges in broad, delta, theta, alpha, and beta frequency bands, characterized the network topology, and used the Hub Disruption Index (HDI) to quantify the topological reorganization. We examined the generalizability of our results by reproducing a 25-electrode clinical system. RESULTS: Our study did not reveal any significant change in whole-brain network topology among GGE patients. However, the HDI was significantly different between patients and controls in all frequency bands except alpha (p < .01, false discovery rate [FDR] corrected, d < -1), and accompanied by an increase in connectivity in the prefrontal regions and default mode network. This reorganization suggests that regions that are important in transferring the information in controls were less so in patients. Inversely, the crucial regions in patients are less so in controls. These findings were also found in delta and theta frequency bands when using 25 electrodes (p < .001, FDR corrected, d < -1). SIGNIFICANCE: In GGE patients, the overall network topology is similar to that of healthy controls but presents a balanced local topological reorganization. This reorganization causes the prefrontal areas and default mode network to be more integrated and segregated, which may explain executive impairment associated with GGE. Additionally, the reorganization distinguishes patients from controls even when using 25 electrodes, suggesting its potential use as a diagnostic tool.

Long-term outcome of alcohol withdrawal seizures.

BACKGROUND AND PURPOSE: Alcohol withdrawal seizures (AWS) are a well-known complication of chronic alcohol abuse, but there is currently little knowledge of their long-term relapse rate and prognosis. The aims of this study were to identify risk factors for AWS recurrence and to study the overall outcome of patients after AWS. METHODS: In this retrospective single-center study, we included patients who were admitted to the Emergency Department after an AWS between January 1, 2013 and August 10, 2021 and for whom an electroencephalogram (EEG) was requested. AWS relapses up until April 29, 2022 were researched. We compared history, treatment with benzodiazepines or antiseizure medications (ASMs), laboratory, EEG and computed tomography findings between patients with AWS relapse (r-AWS) and patients with no AWS relapse (nr-AWS). RESULTS: A total of 199 patients were enrolled (mean age 53 ± 12 years; 78.9% men). AWS relapses occurred in 11% of patients, after a median time of 470.5 days. Brain computed tomography (n = 182) showed pathological findings in 35.7%. Risk factors for relapses were history of previous AWS (p = 0.013), skull fractures (p = 0.004) at the index AWS, and possibly epileptiform EEG abnormalities (p = 0.07). Benzodiazepines or other ASMs, taken before or after the index event, did not differ between the r-AWS and the nr-AWS group. The mortality rate was 2.9%/year of follow-up, which was 13 times higher compared to the general population. Risk factors for death were history of AWS (p < 0.001) and encephalopathic EEG (p = 0.043). CONCLUSIONS: Delayed AWS relapses occur in 11% of patients and are associated with risk factors (previous AWS >24 h apart, skull fractures, and pathological EEG findings) that also increase the epilepsy risk, that is, predisposition for seizures, if not treated. Future prospective studies are mandatory to determine appropriate long-term diagnostic and therapeutic strategies, in order to reduce the risk of relapse and mortality associated with AWS.

Antiseizure medication ≤48 hours portends better prognosis in new-onset epilepsy.

BACKGROUND: Several studies found that patients with new-onset epilepsy (NOE) have higher seizure recurrence rates if they presented already prior seizures. These observations suggest that timing of antiseizure medication (ASM) is crucial and should be offered immediately after the first seizure. Here, we wanted to assess whether immediate ASM is associated with improved outcome. METHODS: Single-center study of 1010 patients (≥16 years) who presented with a possible first seizure in the emergency department between 1 March 2010 and 1 March 2017. A comprehensive workup was launched upon arrival, including routine electroencephalography (EEG), brain computed tomography/magnetic resonance imaging, long-term overnight EEG and specialized consultations. We followed patients for 5 years comparing the relapse rate in patients treated within 48 h to those with treatment >48 h. RESULTS: A total of 487 patients were diagnosed with NOE. Of the 416 patients (162 female, age: 54.6 ± 21.1 years) for whom the treatment start could be retrieved, 80% (333/416) were treated within 48 h. The recurrence rate after immediate treatment (32%; 107/333) was significantly lower than in patients treated later (56.6%; 47/83; p < 0.001). For patients for whom a complete 5-year-follow-up was available (N = 297, 123 female), those treated ≤48 h (N = 228; 76.8%) had a significantly higher chance of remaining seizure-free compared with patients treated later (N = 69; 23.2%; p < 0.001). CONCLUSIONS: In this retrospective study, immediate ASM therapy (i.e., within 48 h) was associated with better prognosis up to 5 years after the index event. Prospective studies are required to determine the value of immediate workup and drug therapy in NOE patients.

Frequency-specific gaze modulation of emotional face processing in the human amygdala.

Determining the social significance of emotional face expression is of major importance for adaptive behavior, and gaze direction provides critical information in this process. The amygdala is implicated in both emotion and gaze processing, but how and when it integrates expression and gaze cues remains unresolved. We tackled this question using intracranial electroencephalography in epileptic patients to assess both amygdala (n = 12) and orbitofrontal cortex (OFC; n = 11) time-frequency evoked responses to faces with different emotional expressions and different gaze directions. As predicted, self-relevant threat signals (averted fearful and directed angry faces) elicited stronger amygdala activity than self-irrelevant threat (directed fearful and averted angry faces). Fear effects started at early latencies in both amygdala and OFC (~110 and 160 ms, respectively), while gaze direction effects and their interaction with emotion occurred at later latencies. Critically, the amygdala showed differential gamma band increases to fearful averted gaze (starting ~550 ms) and to angry directed gaze (~470 ms). Moreover, when comparing the 2 self-relevant threat conditions among them, we found higher gamma amygdala activity for averted fearful faces and higher beta OFC activity for angry directed faces. Together, these results reveal for the first time frequency-specific effects of emotion and gaze on amygdala and OFC neural activity.

Prestimulus amygdala spectral activity is associated with visual face awareness.

Alpha cortical oscillations have been proposed to suppress sensory processing in the visual, auditory, and tactile domains, influencing conscious stimulus perception. However, it is unknown whether oscillatory neural activity in the amygdala, a subcortical structure involved in salience detection, has a similar impact on stimulus awareness. Recording intracranial electroencephalography (EEG) from 9 human amygdalae during face detection in a continuous flash suppression task, we found increased spectral prestimulus power and phase coherence, with most consistent effects in the alpha band, when faces were undetected relative to detected, similarly as previously observed in cortex with this task using scalp-EEG. Moreover, selective decreases in the alpha and gamma bands preceded face detection, with individual prestimulus alpha power correlating negatively with detection rate in patients. These findings reveal for the first time that prestimulus subcortical oscillations localized in human amygdala may contribute to perceptual gating mechanisms governing subsequent face detection and offer promising insights on the role of this structure in visual awareness.

Neurology of Aging : adapting neurology provision for an aging population.

Background Over the past few decades, advances in neurology of aging have been considerable and have led to a better understanding of the science of age-related neurological disorders. Likewise, it changed the perception of classical neurology practice, research and the way of looking at age-related conditions. Neurological disorders are the most frequent cause of major disability in the elderly and account for almost half of the incapacitation occurring beyond age 65 and more than 90% of serious dependency. However, a number of neurological changes occur also in the absence of a specific disease, making the assessment and management of neurological complaints and findings a specific expertise. Summary Maximizing success in clinical care of the elderly requires expertise in geriatric neurology, which includes an understanding of current research regarding aging and age-related neurological dysfunctions, and the ability to work with other geriatric health care providers. Although current therapies for neurodegenerative diseases mainly offer symptomatic relief without slowing progression, the landscape is evolving. Biomarkers of pathology and neuroimaging have continued to develop, with a significant impact on diagnosis and treatment. These advances have helped to improve our knowledge of disease pathophysiology but also disease stages, guiding symptomatic monitoring, and possible therapeutic options at a pre-symptomatic stage. Key Messages Neurological disorders are a leading cause of major disability and dependency in the elderly, underscoring the need for expertise in geriatric neurology for effective clinical care of this population. Although current therapies for neurodegenerative diseases primarily provide symptomatic relief without slowing disease progression, advancements in biomarkers and neuroimaging are significantly evolving. These advancements enhance our understanding of disease pathophysiology and stages, guiding symptomatic monitoring and potential therapeutic options at a pre-symptomatic stage. As knowledge about age-associated conditions is steadily rising and geriatric medicine gains further recognition, this article argues for a new focus on the role of neurologists in geriatric medicine, emphasizing the importance of integrating current research and collaborative care approaches in the management of elderly patients.

Submillimeter T1 atlas for subject-specific abnormality detection at 7T.

PURPOSE: Studies at 3T have shown that T1 relaxometry enables characterization of brain tissues at the single-subject level by comparing individual physical properties to a normative atlas. In this work, an atlas of normative T1 values at 7T is introduced with 0.6 mm isotropic resolution and its clinical potential is explored in comparison to 3T. METHODS: T1 maps were acquired in two separate healthy cohorts scanned at 3T and 7T. Using transfer learning, a template-based brain segmentation algorithm was adapted to ultra-high field imaging data. After segmenting brain tissues, volumes were normalized into a common space, and an atlas of normative T1 values was established by modeling the T1 inter-subject variability. A method for single-subject comparisons restricted to white matter and subcortical structures was developed by computing Z-scores. The comparison was applied to eight patients scanned at both field strengths for proof of concept. RESULTS: The proposed method for morphometry delivered segmentation masks without statistically significant differences from those derived with the original pipeline at 3T and achieved accurate segmentation at 7T. The established normative atlas allowed characterizing tissue alterations in single-subject comparisons at 7T, and showed greater anatomical details compared with 3T results. CONCLUSION: A high-resolution quantitative atlas with an adapted pipeline was introduced and validated. Several case studies on different clinical conditions showed the feasibility, potential and limitations of high-resolution single-subject comparisons based on quantitative MRI atlases. This method in conjunction with 7T higher resolution broadens the range of potential applications of quantitative MRI in clinical practice.

Insular Stimulation Produces Mental Clarity and Bliss.

For the first time, an ecstatic aura has been evoked through the electrical stimulation of the dorsal anterior insula during presurgical invasive intracerebral monitoring in a patient who did not suffer from an ecstatic form of epilepsy. This case provides more evidence that the anterior insula is the major generator of such a mystical-type experience even in individuals with no underlying brain network changes related to a preexisting ecstatic epilepsy. ANN NEUROL 2022;91:289-292.

Semiautomatic interictal electric source localization based on long-term electroencephalographic monitoring: A prospective study.

OBJECTIVE: Electric source imaging (ESI) of interictal epileptiform discharges (IEDs) has shown significant yield in numerous studies; however, its implementation at most centers is labor- and cost-intensive. Semiautomatic ESI analysis (SAEA) has been proposed as an alternative and has previously shown benefit. Computer-assisted automatic spike cluster retrieval, averaging, and source localization are carried out for each cluster and are then reviewed by an expert neurophysiologist, to determine their relevance for the individual case. Here, we examine its yield in a prospective single center study. METHOD: Between 2017 and 2022, 122 patients underwent SAEA. Inclusion criteria for the current study were unifocal epilepsy disorder, epilepsy surgery with curative purpose, and postoperative follow-up of 2 years or more. All patients (N=40) had continuous video-electroencephalographic (EEG) monitoring with 37 scalp electrodes, which underwent SAEA. Forty patients matched our inclusion criteria. RESULTS: Twenty patients required intracranial monitoring; 13 were magnetic resonance imaging (MRI)-negative. Mean duration of analyzed EEG was 4.3 days (±3.1 days), containing a mean of 12 749 detected IEDs (±22 324). The sensitivity, specificity, and accuracy of SAEA for localizing the epileptogenic focus of the entire group were 74.3%, 80%, and 75%, respectively, leading to an odds ratio (OR) of 11.5 to become seizure-free if the source was included in the resection volume (p < .05). In patients with extratemporal lobe epilepsy, our results indicated an accuracy of 68% (OR=11.7). For MRI-negative patients (n = 13) and patients requiring intracranial EEG (n = 20), we found a similarly high accuracy of 84.6% (OR=19) and 75% (OR = 15.9), respectively. SIGNIFICANCE: In this prospective study of SAEA of long-term video-EEG, spanning several days, we found excellent localizing information and a high yield, even in difficult patient groups. This compares favorably to high-density ESI, most likely due to marked improved signal-to-noise ratio of the averaged IEDs. We propose including ESI, or SAEA, in the workup of all patients who are referred for epilepsy surgery.

Added value of advanced workup after the first seizure: A 7-year cohort study.

OBJECTIVE: This study was undertaken to establish whether advanced workup including long-term electroencephalography (LT-EEG) and brain magnetic resonance imaging (MRI) provides an additional yield for the diagnosis of new onset epilepsy (NOE) in patients presenting with a first seizure event (FSE). METHODS: In this population-based study, all adult (≥16 years) patients presenting with FSE in the emergency department (ED) between March 1, 2010 and March 1, 2017 were assessed. Patients with obvious nonepileptic or acute symptomatic seizures were excluded. Routine EEG, LT-EEG, brain computed tomography (CT), and brain MRI were performed as part of the initial workup. These examinations' sensitivity and specificity were calculated on the basis of the final diagnosis after 2 years, along with the added value of advanced workup (MRI and LT-EEG) over routine workup (routine EEG and CT). RESULTS: Of the 1010 patients presenting with FSE in the ED, a definite diagnosis of NOE was obtained for 501 patients (49.6%). Sensitivity of LT-EEG was higher than that of routine EEG (54.39% vs. 25.5%, p < .001). Similarly, sensitivity of MRI was higher than that of CT (67.98% vs. 54.72%, p = .009). Brain MRI showed epileptogenic lesions in an additional 32% compared to brain CT. If only MRI and LT-EEG were considered, five would have been incorrectly diagnosed as nonepileptic (5/100, 5%) compared to patients with routine EEG and MRI (25/100, 25%, p = .0001). In patients with all four examinations, advanced workup provided an overall additional yield of 50% compared to routine workup. SIGNIFICANCE: Our results demonstrate the remarkable added value of the advanced workup launched already in the ED for the diagnosis of NOE versus nonepileptic causes of seizure mimickers. Our findings suggest the benefit of first-seizure tracks or even units with overnight EEG, similar to stroke units, activated upon admission in the ED.

Early timing of anesthesia in status epilepticus is associated with complete recovery: A 7-year retrospective two-center study.

OBJECTIVE: This study was undertaken to investigate the efficacy, tolerability, and outcome of different timing of anesthesia in adult patients with status epilepticus (SE). METHODS: Patients with anesthesia for SE from 2015 to 2021 at two Swiss academic medical centers were categorized as anesthetized as recommended third-line treatment, earlier (as first- or second-line treatment), and delayed (later as third-line treatment). Associations between timing of anesthesia and in-hospital outcomes were estimated by logistic regression. RESULTS: Of 762 patients, 246 received anesthesia; 21% were anesthetized as recommended, 55% earlier, and 24% delayed. Propofol was preferably used for earlier (86% vs. 55.5% for recommended/delayed anesthesia) and midazolam for later anesthesia (17.2% vs. 15.9% for earlier anesthesia). Earlier anesthesia was statistically significantly associated with fewer infections (17% vs. 32.7%), shorter median SE duration (.5 vs. 1.5 days), and more returns to premorbid neurologic function (52.9% vs. 35.5%). Multivariable analyses revealed decreasing odds for return to premorbid function with every additional nonanesthetic antiseizure medication given prior to anesthesia (odds ratio [OR] = .71, 95% confidence interval [CI] = .53-.94) independent of confounders. Subgroup analyses revealed decreased odds for return to premorbid function with increasing delay of anesthesia independent of the Status Epilepticus Severity Score (STESS; STESS = 1-2: OR = .45, 95% CI = .27-.74; STESS > 2: OR = .53, 95% CI = .34-.85), especially in patients without potentially fatal etiology (OR = .5, 95% CI = .35-.73) and in patients experiencing motor symptoms (OR = .67, 95% CI = .48-.93). SIGNIFICANCE: In this SE cohort, anesthetics were administered as recommended third-line therapy in only every fifth patient and earlier in every second. Increasing delay of anesthesia was associated with decreased odds for return to premorbid function, especially in patients with motor symptoms and no potentially fatal etiology.

Sex-related differences in adult patients with status epilepticus: a seven-year two-center observation.

BACKGROUND: Conflicting findings exist regarding the influence of sex on the development, treatment, course, and outcome of status epilepticus (SE). Our study aimed to investigate sex-related disparities in adult SE patients, focusing on treatment, disease course, and outcome at two Swiss academic medical centers. METHODS: In this retrospective study, patients treated for SE at two Swiss academic care centers from Basel and Geneva from 2015 to 2021 were included. Primary outcomes were return to premorbid neurologic function, death during hospital stay and at 30 days. Secondary outcomes included characteristics of treatment and disease course. Associations with primary and secondary outcomes were assessed using multivariable logistic regression. Analysis using propensity score matching was performed to account for the imbalances regarding age between men and women. RESULTS: Among 762 SE patients, 45.9% were women. No sex-related differences were found between men and women, except for older age and lower frequency of intracranial hemorrhages in women. Compared to men, women had a higher median age (70 vs. 66, p = 0.003), had focal nonconvulsive SE without coma more (34.9% vs. 25.5%; p = 0.005) and SE with motor symptoms less often (52.3% vs. 63.6%, p = 0.002). With longer SE duration (1 day vs. 0.5 days, p = 0.011) and a similar proportion of refractory SE compared to men (36.9% vs. 36.4%, p = 0.898), women were anesthetized and mechanically ventilated less often (30.6% vs. 42%, p = 0.001). Age was associated with all primary outcomes in the unmatched multivariable analyses, but not female sex. In contrast, propensity score-matched multivariable analyses revealed decreased odds for return to premorbid neurologic function for women independent of potential confounders. At hospital discharge, women were sent home less (29.7% vs. 43.7%, p < 0.001) and to nursing homes more often (17.1% vs. 10.0%, p = 0.004). CONCLUSIONS: This study identified sex-related disparities in the clinical features, treatment modalities, and outcome of adult patients with SE with women being at a disadvantage, implying that sex-based factors must be considered when formulating strategies for managing SE and forecasting outcomes.

Increased delta power as a scalp marker of epileptic activity: a simultaneous scalp and intracranial electroencephalography study.

BACKGROUND AND PURPOSE: The purpose was to evaluate whether intracranial interictal epileptiform discharges (IEDs) that are not visible on the scalp are associated with changes in the frequency spectrum on scalp electroencephalograms (EEGs). METHODS: Simultaneous scalp high-density EEG and intracranial EEG recordings were recorded in nine patients undergoing pre-surgical invasive recordings for pharmaco-resistant temporal lobe epilepsy. Epochs with hippocampal IED visible on intracranial EEG (ic-IED) but not on scalp EEG were selected, as well as control epochs without ic-IED. Welch's power spectral density was computed for each scalp electrode and for each subject; the power spectral density was further averaged across the canonical frequency bands and compared between the two conditions with and without ic-IED. For each patient the peak frequency in the delta band (the significantly strongest frequency band in all patients) was determined during periods of ic-IED. The five electrodes showing strongest power at the peak frequency were also determined. RESULTS: It was found that intracranial IEDs are associated with an increase in delta power on scalp EEGs, in particular at a frequency ≥1.4 Hz. Electrodes showing slow frequency power changes associated with IEDs were consistent with the hemispheric lateralization of IEDs. Electrodes with maximum power of slow activity were not limited to temporal regions but also involved frontal (bilateral or unilateral) regions. CONCLUSIONS: In patients with a clinical picture suggestive of temporal lobe epilepsy, the presence of delta slowing ≥1.4 Hz in anterior temporal regions can represent a scalp marker of hippocampal IEDs. To our best knowledge this is the first study that demonstrates the co-occurrence of ic-IED and increased delta power.

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.

Focal versus distributed temporal cortex activity for speech sound category assignment.

Percepts and words can be decoded from distributed neural activity measures. However, the existence of widespread representations might conflict with the more classical notions of hierarchical processing and efficient coding, which are especially relevant in speech processing. Using fMRI and magnetoencephalography during syllable identification, we show that sensory and decisional activity colocalize to a restricted part of the posterior superior temporal gyrus (pSTG). Next, using intracortical recordings, we demonstrate that early and focal neural activity in this region distinguishes correct from incorrect decisions and can be machine-decoded to classify syllables. Crucially, significant machine decoding was possible from neuronal activity sampled across different regions of the temporal and frontal lobes, despite weak or absent sensory or decision-related responses. These findings show that speech-sound categorization relies on an efficient readout of focal pSTG neural activity, while more distributed activity patterns, although classifiable by machine learning, instead reflect collateral processes of sensory perception and decision.

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.

The predictive value of hypometabolism in focal epilepsy: a prospective study in surgical candidates.

PURPOSE: FDG PET is an established tool in presurgical epilepsy evaluation, but it is most often used selectively in patients with discordant MRI and EEG results. Interpretation is complicated by the presence of remote or multiple areas of hypometabolism, which leads to doubt as to the true location of the seizure onset zone (SOZ) and might have implications for predicting the surgical outcome. In the current study, we determined the sensitivity and specificity of PET localization prospectively in a consecutive unselected cohort of patients with focal epilepsy undergoing in-depth presurgical evaluation. METHODS: A total of 130 patients who underwent PET imaging between 2006 and 2015 matched our inclusion criteria, and of these, 86 were operated on (72% with a favourable surgical outcome, Engel class I). Areas of focal hypometabolism were identified using statistical parametric mapping and concordance with MRI, EEG and intracranial EEG was evaluated. In the surgically treated patients, postsurgical outcome was used as the gold standard for correctness of localization (minimum follow-up 12 months). RESULTS: PET sensitivity and specificity were both 95% in 86 patients with temporal lobe epilepsy (TLE) and 80% and 95%, respectively, in 44 patients with extratemporal epilepsy (ETLE). Significant extratemporal hypometabolism was observed in 17 TLE patients (20%). Temporal hypometabolism was observed in eight ETLE patients (18%). Among the 86 surgically treated patients, 26 (30%) had hypometabolism extending beyond the SOZ. The presence of unilobar hypometabolism, included in the resection, was predictive of complete seizure control (p = 0.007), with an odds ratio of 5.4. CONCLUSION: Additional hypometabolic areas were found in one of five of this group of nonselected patients with focal epilepsy, including patients with "simple" lesional epilepsy, and this finding should prompt further in-depth evaluation of the correlation between EEG findings, semiology and PET. Hypometabolism confined to the epileptogenic zone as defined by EEG and MRI is associated with a favourable postoperative outcome in both TLE and ETLE patients.

Nicotinic receptor abnormalities as a biomarker in idiopathic generalized epilepsy.

PURPOSE: Mutations of cholinergic neuronal nicotinic receptors have been identified in the autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE), associated with changes on PET images using [18F]-F-85380-A (F-A-85380), an α4ß2 nicotinic receptor ligand. The aim of the present study was to evaluate potential changes in nicotinic receptor availability in other types of epilepsy. METHODS: We included 34 male participants, 12 patients with idiopathic generalized epilepsy (IGE), 10 with non-lesional diurnal focal epilepsy, and 12 age-matched healthy controls. All patients underwent PET/CT using F-A-85380 and [18F]-fluorodeoxyglucose (FDG), 3D T1 MRI and diffusion tensor imaging (DTI). F-A-85380 and FDG images were compared with the control group using a voxel-wise (SPM12) and a volumes of interest (VOI) analysis. RESULTS: In the group of patients with IGE, the voxel-wise and VOI analyses showed a significant increase of F-A-85380 ratio index of binding potential (BPRI, corresponding to the receptor availability) in the anterior cingulate cortex (ACC), without structural changes on MRI. At an individual level, F-A-85380 BPRI increase in the ACC could distinguish IGE patients from controls and from patients with focal epilepsy with good accuracy. CONCLUSIONS: We observed focal changes of density/availability of nicotinic receptors in IGE, namely an increase in the ACC. These data suggest that the modulation of α4ß2 nicotinic receptors plays a role not only in ADNFLE, but also in other genetic epileptic syndromes such as IGE and could serve as a biomarker of epilepsy syndromes with a genetic background.