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As an intrinsic component of sleep architecture, sleep arousals represent an intermediate state between sleep and wakefulness and are important for sleep-wake regulation. They are defined in an all-or-none manner, whereas they actually present a wide range of scalp-electroencephalography (EEG) activity patterns. It is poorly understood how these arousals differ in their mechanisms. Stereo-EEG (SEEG) provides the unique opportunity to record intracranial activities in superficial and deep structures in humans. Using combined polysomnography and SEEG, we quantitatively categorized arousals during nonrapid eye movement sleep into slow wave (SW) and non-SW arousals based on whether they co-occurred with a scalp-EEG SW event. We then investigated their intracranial correlates in up to 26 brain regions from 26 patients (12 females). Across both arousal types, intracranial theta, alpha, sigma, and beta activities increased in up to 25 regions (p < 0.05; d = 0.06-0.63), while gamma and high-frequency (HF) activities decreased in up to 18 regions across the five brain lobes (p < 0.05; d = 0.06-0.44). Intracranial delta power widely increased across five lobes during SW arousals (p < 0.05 in 22 regions; d = 0.10-0.39), while it widely decreased during non-SW arousals (pâ <â 0.05 in 19 regions; d = 0.10-0.30). Despite these main patterns, unique activities were observed locally in some regions such as the hippocampus and middle cingulate cortex, indicating spatial heterogeneity of arousal responses. Our results suggest that non-SW arousals correspond to a higher level of brain activation than SW arousals. The decrease in HF activities could potentially explain the absence of awareness and recollection during arousals.
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Eletrocorticografia , Couro Cabeludo , Feminino , Humanos , Sono/fisiologia , Nível de Alerta/fisiologia , Vigília/fisiologia , Eletroencefalografia/métodosRESUMO
Electro/Magneto-EncephaloGraphy (EEG/MEG) source imaging (EMSI) of epileptic activity from deep generators is often challenging due to the higher sensitivity of EEG/MEG to superficial regions and to the spatial configuration of subcortical structures. We previously demonstrated the ability of the coherent Maximum Entropy on the Mean (cMEM) method to accurately localize the superficial cortical generators and their spatial extent. Here, we propose a depth-weighted adaptation of cMEM to localize deep generators more accurately. These methods were evaluated using realistic MEG/high-density EEG (HD-EEG) simulations of epileptic activity and actual MEG/HD-EEG recordings from patients with focal epilepsy. We incorporated depth-weighting within the MEM framework to compensate for its preference for superficial generators. We also included a mesh of both hippocampi, as an additional deep structure in the source model. We generated 5400 realistic simulations of interictal epileptic discharges for MEG and HD-EEG involving a wide range of spatial extents and signal-to-noise ratio (SNR) levels, before investigating EMSI on clinical HD-EEG in 16 patients and MEG in 14 patients. Clinical interictal epileptic discharges were marked by visual inspection. We applied three EMSI methods: cMEM, depth-weighted cMEM and depth-weighted minimum norm estimate (MNE). The ground truth was defined as the true simulated generator or as a drawn region based on clinical information available for patients. For deep sources, depth-weighted cMEM improved the localization when compared to cMEM and depth-weighted MNE, whereas depth-weighted cMEM did not deteriorate localization accuracy for superficial regions. For patients' data, we observed improvement in localization for deep sources, especially for the patients with mesial temporal epilepsy, for which cMEM failed to reconstruct the initial generator in the hippocampus. Depth weighting was more crucial for MEG (gradiometers) than for HD-EEG. Similar findings were found when considering depth weighting for the wavelet extension of MEM. In conclusion, depth-weighted cMEM improved the localization of deep sources without or with minimal deterioration of the localization of the superficial sources. This was demonstrated using extensive simulations with MEG and HD-EEG and clinical MEG and HD-EEG for epilepsy patients.
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Eletroencefalografia , Entropia , Magnetoencefalografia , Humanos , Magnetoencefalografia/métodos , Eletroencefalografia/métodos , Adulto , Feminino , Masculino , Simulação por Computador , Adulto Jovem , Epilepsia/fisiopatologia , Epilepsia/diagnóstico por imagem , Pessoa de Meia-Idade , Mapeamento Encefálico/métodos , Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Hipocampo/diagnóstico por imagem , Hipocampo/fisiopatologia , Modelos NeurológicosRESUMO
OBJECTIVE: Sleep has important influences on focal interictal epileptiform discharges (IEDs), and the rates and spatial extent of IEDs are increased in non-rapid eye movement (NREM) sleep. In contrast, the influence of sleep on seizures is less clear, and its effects on seizure topography are poorly documented. We evaluated the influences of NREM sleep on ictal spatiotemporal dynamics and contrasted these with interictal network dynamics. METHODS: We included patients with drug-resistant focal epilepsy who underwent continuous intracranial electroencephalography (iEEG) with depth electrodes. Patients were selected if they had 1 to 3 seizures from each vigilance state, wakefulness and NREM sleep, within a 48-hour window, and under the same antiseizure medication. A 10-minute epoch of the interictal iEEG was selected per state, and IEDs were detected automatically. A total of 25 patients (13 women; aged 32.5 ± 7.1 years) were included. RESULTS: The seizure onset pattern, duration, spatiotemporal propagation, and latency of ictal high-frequency activity did not differ significantly between wakefulness and NREM sleep (all p > 0.05). In contrast, IED rates and spatial distribution were increased in NREM compared with wakefulness (p < 0.001, Cliff's d = 0.48 and 0.49). The spatial overlap between vigilance states was higher for seizures (57.1 ± 40.1%) than IEDs (41.7 ± 46.2%; p = 0.001, Cliff's d = 0.51). INTERPRETATION: In contrast to its effects on IEDs, NREM sleep does not affect ictal spatiotemporal dynamics. This suggests that once the brain surpasses the seizure threshold, it will follow the underlying epileptic network irrespective of the vigilance state. These findings offer valuable insights into neural network dynamics in epilepsy and have important clinical implications for localizing seizure foci. ANN NEUROL 2023.
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OBJECTIVE: Epileptic spikes are the traditional interictal electroencephalographic (EEG) biomarker for epilepsy. Given their low specificity for identifying the epileptogenic zone (EZ), they are given only moderate attention in presurgical evaluation. This study aims to demonstrate that it is possible to identify specific spike features in intracranial EEG that optimally define the EZ and predict surgical outcome. METHODS: We analyzed spike features on stereo-EEG segments from 83 operated patients from 2 epilepsy centers (37 Engel IA) in wakefulness, non-rapid eye movement sleep, and rapid eye movement sleep. After automated spike detection, we investigated 135 spike features based on rate, morphology, propagation, and energy to determine the best feature or feature combination to discriminate the EZ in seizure-free and non-seizure-free patients by applying 4-fold cross-validation. RESULTS: The rate of spikes with preceding gamma activity in wakefulness performed better for surgical outcome classification (4-fold area under receiver operating characteristics curve [AUC] = 0.755 ± 0.07) than the seizure onset zone, the current gold standard (AUC = 0.563 ± 0.05, p = 0.015) and the ripple rate, an emerging seizure-independent biomarker (AUC = 0.537 ± 0.07, p = 0.006). Channels with a spike-gamma rate exceeding 1.9/min had an 80% probability of being in the EZ. Combining features did not improve the results. INTERPRETATION: Resection of brain regions with high spike-gamma rates in wakefulness is associated with a high probability of achieving seizure freedom. This rate could be applied to determine the minimal number of spiking channels requiring resection. In addition to quantitative analysis, this feature is easily accessible to visual analysis, which could aid clinicians during presurgical evaluation. ANN NEUROL 2023;93:522-535.
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Epilepsia , Humanos , Epilepsia/cirurgia , Convulsões/diagnóstico , Eletroencefalografia/métodos , Encéfalo/cirurgia , BiomarcadoresRESUMO
OBJECTIVE: The automated interpretation of clinical electroencephalograms (EEGs) using artificial intelligence (AI) holds the potential to bridge the treatment gap in resource-limited settings and reduce the workload at specialized centers. However, to facilitate broad clinical implementation, it is essential to establish generalizability across diverse patient populations and equipment. We assessed whether SCORE-AI demonstrates diagnostic accuracy comparable to that of experts when applied to a geographically different patient population, recorded with distinct EEG equipment and technical settings. METHODS: We assessed the diagnostic accuracy of a "fixed-and-frozen" AI model, using an independent dataset and external gold standard, and benchmarked it against three experts blinded to all other data. The dataset comprised 50% normal and 50% abnormal routine EEGs, equally distributed among the four major classes of EEG abnormalities (focal epileptiform, generalized epileptiform, focal nonepileptiform, and diffuse nonepileptiform). To assess diagnostic accuracy, we computed sensitivity, specificity, and accuracy of the AI model and the experts against the external gold standard. RESULTS: We analyzed EEGs from 104 patients (64 females, median age = 38.6 [range = 16-91] years). SCORE-AI performed equally well compared to the experts, with an overall accuracy of 92% (95% confidence interval [CI] = 90%-94%) versus 94% (95% CI = 92%-96%). There was no significant difference between SCORE-AI and the experts for any metric or category. SCORE-AI performed well independently of the vigilance state (false classification during awake: 5/41 [12.2%], false classification during sleep: 2/11 [18.2%]; p = .63) and normal variants (false classification in presence of normal variants: 4/14 [28.6%], false classification in absence of normal variants: 3/38 [7.9%]; p = .07). SIGNIFICANCE: SCORE-AI achieved diagnostic performance equal to human experts in an EEG dataset independent of the development dataset, in a geographically distinct patient population, recorded with different equipment and technical settings than the development dataset.
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OBJECTIVE: Rapid eye movement (REM) sleep reduces the rate and extent of interictal epileptiform discharges (IEDs). Breakthrough epileptic activity during REM sleep is therefore thought to best localize the seizure onset zone (SOZ). We utilized polysomnography combined with direct cortical recordings to investigate the influences of anatomical locations and the time of night on the suppressive effect of REM sleep on IEDs. METHODS: Forty consecutive patients with drug-resistant focal epilepsy underwent combined polysomnography and stereo-electroencephalography during presurgical evaluation. Ten-minute interictal epochs were selected 2 h prior to sleep onset (wakefulness), and from the first and second half of the night during non-REM (NREM) sleep and REM sleep. IEDs were detected automatically across all channels. Anatomic localization, time of night, and channel type (within or outside the SOZ) were tested as modulating factors. RESULTS: Relative to wakefulness, there was a suppression of IEDs by REM sleep in neocortical regions (median = -27.6%), whereas mesiotemporal regions showed an increase in IEDs (19.1%, p = .01, d = .39). This effect was reversed when comparing the regional suppression of IEDs by REM sleep relative to NREM sleep (-35.1% in neocortical, -58.7% in mesiotemporal, p < .001, d = .39). Across all patients, no clinically relevant novel IED regions were observed in REM sleep versus NREM or wakefulness based on our predetermined thresholds (4 IEDs/min in REM, 0 IEDs/min in NREM and wakefulness). Finally, there was a reduction in IEDs in late (NREM: 1.08/min, REM: .61/min) compared to early sleep (NREM: 1.22/min, REM: .69/min) for both NREM (p < .001, d = .21) and REM (p = .04, d = .14). SIGNIFICANCE: Our results demonstrate a spatiotemporal effect of IED suppression by REM sleep relative to wakefulness in neocortical but not mesiotemporal regions, and in late versus early sleep. This suggests the importance of considering sleep stage interactions and the potential influences of anatomical locations when using IEDs to define the epileptic focus.
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Epilepsia Resistente a Medicamentos , Epilepsia , Neocórtex , Humanos , Sono REM , Sono , Eletroencefalografia/métodosRESUMO
Seminal animal studies demonstrated the role of sleep oscillations such as cortical slow waves, thalamocortical spindles, and hippocampal ripples in memory consolidation. In humans, whether ripples are involved in sleep-related memory processes is less clear. Here, we explored the interactions between sleep oscillations (measured as traits) and general episodic memory abilities in 26 adults with drug-resistant temporal lobe epilepsy who performed scalp-intracranial electroencephalographic recordings and neuropsychological testing, including two analogous hippocampal-dependent verbal and nonverbal memory tasks. We explored the relationships between hemispheric scalp (spindles, slow waves) and hippocampal physiological and pathological oscillations (spindles, slow waves, ripples, and epileptic spikes) and material-specific memory function. To differentiate physiological from pathological ripples, we used multiple unbiased data-driven clustering approaches. At the individual level, we found material-specific cerebral lateralization effects (left-verbal memory, right-nonverbal memory) for all scalp spindles (rs > 0.51, ps < 0.01) and fast spindles (rs > 0.61, ps < 0.002). Hippocampal epileptic spikes and short pathological ripples, but not physiological oscillations, were negatively (rs > -0.59, ps < 0.01) associated with verbal learning and retention scores, with left lateralizing and antero-posterior effects. However, data-driven clustering failed to separate the ripple events into defined clusters. Correlation analyses with the resulting clusters revealed no meaningful or significant associations with the memory scores. Our results corroborate the role of scalp spindles in memory processes in patients with drug-resistant temporal lobe epilepsy. Yet, physiological and pathological ripples were not separable when using data-driven clustering, and thus our findings do not provide support for a role of sleep ripples as trait-like characteristics of general memory abilities in epilepsy.
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Epilepsia do Lobo Temporal , Epilepsia , Consolidação da Memória , Memória Episódica , Adulto , Animais , Humanos , Couro Cabeludo , Eletroencefalografia/métodos , Hipocampo/fisiologia , Sono/fisiologiaRESUMO
OBJECTIVE: Corticosteroids and adrenocorticotropic hormone (ACTH) are the therapy of choice to treat infantile spasms. However, systematic studies about their use in other types of childhood epilepsies remain rare and ACTH can have serious side effects. This study compares the interictal epileptic activity (IEA) burden (% of electroencephalography (EEG) time with IEDs) in children with genetic drug-resistant epilepsy before and after a standardized treatment with pulsatile corticoid therapy (PCT). METHODS: Children with drug-resistant epilepsy underwent a standardized protocol for PCT with cycles of high-dose dexamethasone (20 mg/m2 body surface) intravenously. Patients were hospitalized for 3 days per PCT cycle and EEGs were obtained before initiation of treatment (baseline) and during the hospitalization around the time of every second cycle. EEG recordings during sleep and wakefulness were obtained. IEA burden was compared before and after PCT. Secondary outcome measures included the sleep spindle rate, the seizure frequency and subjective evaluation in a standardized interview. RESULTS: In the cohort of 24 children (10 female, 6.2 ± 3.4 years), IEA burden was lower in the EEG after PCT compared to the baseline (baseline: 5.4% [0.7-97.3] vs. after PCT: 1.5% [0-96.9], p = 0.001, d = -0.41). Sleep physiology expressed by sleep spindles improved after PCT with enhanced fast spindle rates (0.8/min [0-2.2] vs. 1.5/min [0.2-3.4], p = 0.045, d = 0.36). Seizure frequency was decreased in 17 of the 24 patients (70.8%) with one patient achieving seizure freedom. The majority of patients improved in quality of life (79.2%), and sleep (81.3%). No serious adverse effects were documented. SIGNIFICANCE: This study systematically assessed the effect of PCT in children with genetic / suspected genetic drug-resistant epilepsy. PCT was found to not only reduce the IEA burden but also increase sleep spindle rates, which are important for cognitive functioning. PLAIN LANGUAGE SUMMARY: In this study, children with a form of epilepsy, which is resistant against antiseizure medication, received a systematic treatment with corticosteroids over multiple cycles in the hospital. It was found that not only the epileptic activity was reduced but also the sleep of the patients was improved after the treatment. These findings could provide the basis for extending the use of corticosteroids in children with epilepsy.
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Dexametasona , Epilepsia Resistente a Medicamentos , Eletroencefalografia , Humanos , Feminino , Masculino , Epilepsia Resistente a Medicamentos/tratamento farmacológico , Criança , Dexametasona/uso terapêutico , Pré-Escolar , Corticosteroides/uso terapêutico , Corticosteroides/administração & dosagem , Resultado do Tratamento , Anticonvulsivantes/uso terapêuticoRESUMO
OBJECTIVE: The use of electrical source imaging (ESI) in assessing the source of interictal epileptic discharges (IEDs) is gaining increasing popularity in presurgical work-up of patients with drug-resistant focal epilepsy. While vigilance affects the ability to locate IEDs and identify the epileptogenic zone, we know little about its impact on ESI. METHODS: We studied overnight high-density electroencephalography recordings in focal drug-resistant epilepsy. IEDs were marked visually in each vigilance state, and examined in the sensor and source space. ESIs were calculated and compared between all vigilance states and the clinical ground truth. Two conditions were considered within each vigilance state, an unequalized and an equalized number of IEDs. RESULTS: The number, amplitude, and duration of IEDs were affected by the vigilance state, with N3 sleep presenting the highest number, amplitude, and duration for both conditions (P < 0.001), while signal-to-noise ratio only differed in the unequalized condition (P < 0.001). The vigilance state did not affect channel involvement (P > 0.05). ESI maps showed no differences in distance, quality, extent, or maxima distances compared to the clinical ground truth for both conditions (P > 0.05). Only when an absolute reference (wakefulness) was used, the channel involvement (P < 0.05) and ESI source extent (P < 0.01) were impacted during rapid-eye-movement (REM) sleep. Clustering of amplitude-sensitive and -insensitive ESI maps pointed to amplitude rather than the spatial profile as the driver (P < 0.05). INTERPRETATION: IED ESI results are stable across vigilance states, including REM sleep, if controlled for amplitude and IED number. ESI is thus stable and invariant to the vigilance state.
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Epilepsia Resistente a Medicamentos , Epilepsia , Humanos , Vigília , Eletroencefalografia/métodos , Epilepsia Resistente a Medicamentos/cirurgia , Sono REMRESUMO
Well-documented sleep datasets from healthy adults are important for sleep pattern analysis and comparison with a wide range of neuropsychiatric disorders. Currently, available sleep datasets from healthy adults are acquired using low-density arrays with a minimum of four electrodes in a typical sleep montage. The low spatial resolution is thus prohibitive for the analysis of the spatial structure of sleep. Here we introduce an open-access sleep dataset from 29 healthy adults (13 female, aged 32.17 ± 6.30 years) acquired at the Montreal Neurological Institute. The dataset includes overnight polysomnograms with high-density scalp electroencephalograms incorporating 83 electrodes, electrocardiogram, electromyogram, electrooculogram, and an average of electrode positions using manual co-registrations and sleep scoring annotations. Data characteristics and group-level analysis of sleep properties were assessed. The database can be accessed through ( https://doi.org/10.17605/OSF.IO/R26FH ). This is the first high-density electroencephalogram open sleep database from healthy adults, allowing researchers to investigate sleep physiology at high spatial resolution. We expect that this database will serve as a valuable resource for studying sleep physiology and for benchmarking sleep pathology.
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Eletroencefalografia , Polissonografia , Couro Cabeludo , Sono , Humanos , Adulto , Feminino , Masculino , Bases de Dados FactuaisRESUMO
Stereo-electroencephalography (SEEG) is the gold standard to delineate surgical targets in focal drug-resistant epilepsy. SEEG uses electrodes placed directly into the brain to identify the seizure-onset zone (SOZ). However, its major constraint is limited brain coverage, potentially leading to misidentification of the 'true' SOZ. Here, we propose a framework to assess adequate SEEG sampling by coupling epileptic biomarkers with their spatial distribution and measuring the system's response to a perturbation of this coupling. We demonstrate that the system's response is strongest in well-sampled patients when virtually removing the measured SOZ. We then introduce the spatial perturbation map, a tool that enables qualitative assessment of the implantation coverage. Probability modelling reveals a higher likelihood of well-implanted SOZs in seizure-free patients or non-seizure free patients with incomplete SOZ resections, compared to non-seizure-free patients with complete resections. This highlights the framework's value in sparing patients from unsuccessful surgeries resulting from poor SEEG coverage.
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Encéfalo , Epilepsia Resistente a Medicamentos , Eletrodos Implantados , Eletroencefalografia , Humanos , Eletroencefalografia/métodos , Epilepsia Resistente a Medicamentos/cirurgia , Epilepsia Resistente a Medicamentos/fisiopatologia , Encéfalo/cirurgia , Encéfalo/fisiopatologia , Feminino , Masculino , Adulto , Convulsões/cirurgia , Convulsões/fisiopatologia , Adulto Jovem , Epilepsias Parciais/cirurgia , Epilepsias Parciais/fisiopatologia , Mapeamento Encefálico/métodos , AdolescenteRESUMO
STUDY OBJECTIVES: Whereas there is plenty of evidence on the influence of epileptic activity on non-rapid eye movement (NREM) sleep macro- and micro-structure, data on the impact of epilepsy on rapid eye movement (REM) sleep remains sparse. Using high-density electroencephalography (HD-EEG), we assessed global and focal disturbances of sawtooth waves (STW) as cortically generated sleep oscillations of REM sleep in patients with focal epilepsy. METHODS: Twenty-two patients with drug-resistant focal epilepsy (13 females; mean age, 32.6 ± 10.7 years; 12 temporal lobe epilepsy) and 12 healthy controls (3 females; 24.0 ± 3.2 years) underwent combined overnight HD-EEG and polysomnography. STW rate, duration, frequency, power, spatial extent, IED rates and sleep homeostatic properties were analyzed. RESULTS: STW rate and duration were reduced in patients with focal epilepsy compared to healthy controls (rate: 0.64/min ± 0.46 vs. 1.12/min ± 0.41, p = .005, d = -0.98; duration: 3.60 s ± 0.76 vs. 4.57 ± 1.00, p = .003, d = -1.01). Not surprisingly given the fronto-central maximum of STW, the reductions were driven by extratemporal lobe epilepsy patients (rate: 0.45/min ± 0.31 vs. 1.12/min ± 0.41, p = .0004, d = -1.35; duration: 3.49 s ± 0.92 vs. 4.57 ± 1.00, p = .017, d = -0.99) and were more pronounced in the first vs. the last sleep cycle (rate first cycle patients vs. controls: 0.60/min ± 0.49 vs. 1.10/min ± 0.55, p = .016, d = -0.90, rate last cycle patients vs. controls: 0.67/min ± 0.51 vs. 0.99/min ± 0.49, p = .11, d = -0.62; duration first cycle patients vs. controls: 3.60s ± 0.76 vs. 4.57 ± 1.00, p = .003, d = -1.01, duration last cycle patients vs. controls: 3.66s ± 0.84 vs. 4.51 ± 1.26, p = .039, d = -0.80). There was no regional decrease of STWs in the region with the epileptic focus vs. the contralateral side (all p > .05). CONCLUSION: Patients with focal epilepsy and in particular extratemporal lobe epilepsy show a global reduction of STW activity in REM sleep. This may suggest that epilepsy impacts cortically generated sleep oscillations even in REM sleep when epileptic activity is low.
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Epilepsias Parciais , Epilepsia , Feminino , Humanos , Adulto Jovem , Adulto , Sono REM , Movimentos Oculares , Sono , Eletroencefalografia , ConvulsõesRESUMO
Although general anesthesia is normally induced by systemic dosing, an anesthetic state can be induced in rodents by microinjecting minute quantities of GABAergic agents into the brainstem mesopontine tegmental anesthesia area (MPTA). Correspondingly, lesions to the MPTA render rats relatively insensitive to standard anesthetic doses delivered systemically. Using a chemogenetic approach we have identified and characterized a small subpopulation of neurons restricted to the MPTA which, when excited, render the animal anesthetic by sensorimotor (immobility) and electroencephalographic (EEG) criteria. These "effector-neurons" do not express GABAAδ-Rs, the likely target of GABAergic anesthetics. Rather, we report a distinct sub-population of nearby MPTA neurons which do. During anesthetic induction these likely excite the effector-neurons by disinhibition. Within the effector population ~ 70% appear to be glutamatergic, ~30% GABAergic and ~ 40% glycinergic. Most are projection neurons that send ascending or descending axons to distant targets associated with the individual functional components of general anesthesia: atonia, analgesia, amnesia, and loss-of-consciousness.
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Anestésicos , Estado de Consciência , Anestesia Geral , Anestésicos/efeitos adversos , Animais , Estado de Consciência/fisiologia , Neurônios , Ratos , Ratos Wistar , Inconsciência/induzido quimicamenteRESUMO
Ketogenic diet (KD) and pulsatile dexamethasone therapy (PDT) are commonly used in the treatment of children with drug resistant epilepsy. Potential side effects of the KD are hypoglycemia, whereas PDT might lead to hyperglycemia. One practical option to measure glucose concentrations regularly is the flash glucose monitoring system (FGM). In this single-center study in Germany, two pediatric patients with epilepsy (age: 6.0 and 6.8 years) received FGM from the beginning of the KD over six months, in the year 2020, and one patient (9.8 years) was observed for one month on PDT and switched to the KD thereafter. Glucose concentrations were measured by using an FGM system and capillary blood measurement. Seizure frequency, changes in cognition, motor performance, social behavior, and sleep quality were evaluated. The mean hypoglycemia rate per day (65 mg/dL and lower) declined significantly in patient 1 and 2 after three months. Patient 3 showed in total seven hyperglycemic events during PDT. Patient 1 became seizure free. Improvement of attention and memory performance were reported. FGM during the KD as a treatment for drug resistant epilepsies in childhood is a practical option to explore and to avoid hypoglycemia during the KD and hyperglycemia during PDT.
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Sleep spindles are the hallmark of N2 sleep and are attributed a key role in cognition. Little is known about the impact of epilepsy on sleep oscillations underlying sleep-related functions. This study assessed changes in the global spindle rate in patients with epilepsy, analysed the distribution of spindles in relation to the epileptic focus, and performed correlations with neurocognitive function. Twenty-one patients with drug-resistant focal epilepsy (12 females; mean age 32.6 ± 10.7 years [mean ± SD]) and 12 healthy controls (3 females; 24.5 ± 3.3 years) underwent combined whole-night high-density electroencephalography and polysomnography. Global spindle rates during N2 were lower in epilepsy patients compared to controls (mean = 5.78/min ± 0.72 vs. 6.49/min ± 0.71, p = 0.02, d = - 0.70). Within epilepsy patients, spindle rates were lower in the region of the epileptic focus compared to the contralateral region (median = 4.77/min [range 2.53-6.18] vs. 5.26/min [2.53-6.56], p = 0.02, rank biserial correlation RC = - 0.57). This decrease was driven by fast spindles (12-16 Hz) (1.50/min [0.62-4.08] vs. 1.65/min [0.51-4.28], p = 0.002, RC = - 0.76). The focal reduction in spindles was negatively correlated with two scales of attention (r = - 0.54, p = 0.01; r = - 0.51, p = 0.025). Patients with focal epilepsy show a reduction in global and local spindle rates dependent on the region of the epileptic focus. This may play a role in impaired cognitive functioning. Future work will show if the local reduction in spindles can be used as potential marker of the epileptic focus.
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Epilepsia Resistente a Medicamentos , Epilepsias Parciais , Epilepsia , Adulto , Eletroencefalografia , Feminino , Humanos , Polissonografia , Fases do Sono , Adulto JovemRESUMO
Importance: Stereoelectroencephalography (SEEG) has become the criterion standard in case of inconclusive noninvasive presurgical epilepsy workup. However, up to 40% of patients are subsequently not offered surgery because the seizure-onset zone is less focal than expected or cannot be identified. Objective: To predict focality of the seizure-onset zone in SEEG, the 5-point 5-SENSE score was developed and validated. Design, Setting, and Participants: This was a monocentric cohort study for score development followed by multicenter validation with patient selection intervals between February 2002 to October 2018 and May 2002 to December 2019. The minimum follow-up period was 1 year. Patients with drug-resistant epilepsy undergoing SEEG at the Montreal Neurological Institute were analyzed to identify a focal seizure-onset zone. Selection criteria were 2 or more seizures in electroencephalography and availability of complete neuropsychological and neuroimaging data sets. For validation, patients from 9 epilepsy centers meeting these criteria were included. Analysis took place between May and July 2021. Main Outcomes and Measures: Based on SEEG, patients were grouped as focal and nonfocal seizure-onset zone. Demographic, clinical, electroencephalography, neuroimaging, and neuropsychology data were analyzed, and a multiple logistic regression model for developing a score to predict SEEG focality was created and validated in an independent sample. Results: A total of 128 patients (57 women [44.5%]; median [range] age, 31 [13-58] years) were analyzed for score development and 207 patients (97 women [46.9%]; median [range] age, 32 [16-70] years) were analyzed for validation. The score comprised the following 5 predictive variables: focal lesion on structural magnetic resonance imaging, absence of bilateral independent spikes in scalp electroencephalography, localizing neuropsychological deficit, strongly localizing semiology, and regional ictal scalp electroencephalography onset. The 5-SENSE score had an optimal mean (SD) probability cutoff for identifying a focal seizure-onset zone of 37.6 (3.5). Area under the curve, specificity, and sensitivity were 0.83, 76.3% (95% CI, 66.7-85.8), and 83.3% (95% CI, 72.30-94.1), respectively. Validation showed 76.0% (95% CI, 67.5-84.0) specificity and 52.3% (95% CI, 43.0-61.5) sensitivity. Conclusions and Relevance: High specificity in score development and validation confirms that the 5-SENSE score predicts patients where SEEG is unlikely to identify a focal seizure-onset zone. It is a simple and useful tool for assisting clinicians to reduce unnecessary invasive diagnostic burden on patients and overutilization of limited health care resources.
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Eletroencefalografia , Epilepsia/diagnóstico , Convulsões/diagnóstico , Inquéritos e Questionários/normas , Estudos de Coortes , Epilepsia/cirurgia , Feminino , Humanos , Masculino , Cuidados Pré-Operatórios , Convulsões/cirurgiaRESUMO
General anesthetic agents are thought to induce loss-of-consciousness (LOC) and enable pain-free surgery by acting on the endogenous brain circuitry responsible for sleep-wake cycling. In clinical use, the entire CNS is exposed to anesthetic molecules with LOC and amnesia usually attributed to synaptic suppression in the cerebral cortex and immobility and analgesia to agent action in the spinal cord and brainstem. This model of patch-wise suppression has been challenged, however, by the observation that all functional components of anesthesia can be induced by focal delivery of minute quantities of GABAergic agonists to the brainstem mesopontine tegmental anesthesia area (MPTA). We compared spectral features of the cortical electroencephalogram (EEG) in rats during systemic anesthesia and anesthesia induced by MPTA microinjection. Systemic administration of (GABAergic) pentobarbital yielded the sustained, δ-band dominant EEG signature familiar in clinical anesthesia. In contrast, anesthesia induced by MPTA microinjection (pentobarbital or muscimol) featured epochs of δ-band EEG alternating with the wake-like EEG, the pattern typical of natural non-rapid-eye-movement (NREM) and REM sleep. The rats were not sleeping, however, as they remained immobile, atonic and unresponsive to noxious pinch. Recalling the paradoxical wake-like quality the EEG during REM sleep, we refer to this state as "paradoxical anesthesia". GABAergic anesthetics appear to co-opt both cortical and spinal components of the sleep network via dedicated axonal pathways driven by MPTA neurons. Direct drug exposure of cortical and spinal neurons is not necessary, and is probably responsible for off-target side-effects of systemic administration including monotonous δ-band EEG, hypothermia and respiratory depression. SIGNIFICANCE STATEMENT: The concept that GABAergic general anesthetic agents induce loss-of-consciousness by substituting for an endogenous neurotransmitter, thereby co-opting neural circuitry responsible for sleep-wake transitions, has gained considerable traction. However, the electroencephalographic (EEG) signatures of sleep and anesthesia differ fundamentally. We show that when the anesthetic state is generated by focal delivery of GABAergics into the mesopontine tegmental anesthesia area (MPTA) the resulting EEG repeatedly transitions between delta-wave-dominant and wake-like patterns much as in REM-NREM sleep. This suggests that systemic (clinical) anesthetic delivery, which indiscriminately floods the entire cerebrum with powerful inhibitory agents, obscures the sleep-like EEG signature associated with the less adulterated form of anesthesia obtained when the drugs are applied selectively to loci where the effective neurotransmitter substitution actually occurs.
Assuntos
Anestesia/métodos , Tronco Encefálico/efeitos dos fármacos , Eletroencefalografia/efeitos dos fármacos , GABAérgicos/administração & dosagem , Microinjeções/métodos , Fases do Sono/efeitos dos fármacos , Animais , Tronco Encefálico/fisiologia , Eletroencefalografia/métodos , Feminino , Masculino , Ratos , Ratos Wistar , Reflexo de Endireitamento/efeitos dos fármacos , Reflexo de Endireitamento/fisiologia , Fases do Sono/fisiologiaRESUMO
OBJECTIVE: Fast Oscillations (FO) >40 Hz are a promising biomarker of the epileptogenic zone (EZ). Evidence using scalp electroencephalography (EEG) remains scarce. We assessed if electrical source imaging of FO using 256-channel high-density EEG (HD-EEG) is useful for EZ identification. METHODS: We analyzed HD-EEG recordings of 10 focal drug-resistant epilepsy patients with seizure-free postsurgical outcome. We marked FO candidate events at the time of epileptic spikes and verified them by screening for an isolated peak in the time-frequency plot. We performed electrical source imaging of spikes and FO within the Maximum Entropy of the Mean framework. Source localization maps were validated against the surgical cavity. RESULTS: We identified FO in five out of 10 patients who had a superficial or intermediate deep generator. The maximum of the FO maps was localized inside the cavity in all patients (100%). Analysis with a reduced electrode coverage using the 10-10 and 10-20 system showed a decreased localization accuracy of 60% and 40% respectively. CONCLUSIONS: FO recorded with HD-EEG localize the EZ. HD-EEG is better suited to detect and localize FO than conventional EEG approaches. SIGNIFICANCE: This study acts as proof-of-concept that FO localization using 256-channel HD-EEG is a viable marker of the EZ.
Assuntos
Mapeamento Encefálico/métodos , Epilepsia Resistente a Medicamentos/fisiopatologia , Eletroencefalografia/métodos , Adolescente , Adulto , Criança , Epilepsia Resistente a Medicamentos/diagnóstico , Epilepsia Resistente a Medicamentos/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética/métodosRESUMO
The induction of general anesthesia shares many features with the transition from wakefulness to non-rapid eye movement (NREM) sleep, suggesting that the two types of brain-state transition are orchestrated by a common neuronal mechanism. Previous studies revealed a brainstem locus, the mesopontine tegmental anesthesia area (MPTA), that is of singular importance for anesthetic induction. Microinjection of GABAergic anesthetics there induces rapid loss-of-consciousness and lesions render the animal relatively insensitive to anesthetics administered systemically. Here we show that MPTA lesions also alter the natural sleep-wake rhythm by increasing overall wake time at the expense of time asleep (NREM and REM sleep equally), with nearly all of the change occurring during the dark hours of the light-dark cycle. The effect was proportional to the extent of the lesion and was not seen after lesions just outside of the MPTA, or following sham lesions. Thus, MPTA neurons appear to play a role in natural bistable brain-state switching (sleep-wake) as well as in loss and recovery of consciousness induced pharmacologically.