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OBJECTIVE: This study was undertaken to assess the effect of treatment of vitamin D deficiency in drug-resistant epilepsy. METHODS: We conducted a multicenter, double-blind, placebo-controlled, randomized clinical trial, including patients aged ≥15 years with drug-resistant focal or generalized epilepsy. Patients with 25-hydroxyvitamin D (25[OH]D) < 30 ng/mL were randomized to an experimental group (EG) receiving vitamin D3 (cholecalciferol, 100 000 IU, five doses in 3 months) or a control group (CG) receiving matched placebo. During the open-label study, EG patients received 100 000 IU/month for 6 months, whereas CG patients received five doses in 3 months then 1/month for 3 months. Monitoring included seizure frequency (SF), 25(OH)D, calcium, albumin, creatinine assays, and standardized scales for fatigue, anxiety-depression, and quality of life (Modified Fatigue Impact Scale [M-FIS], Hospital Anxiety and Depression Scale, Quality of Life in Epilepsy [QOLIE-31]) at 3, 6, and 12 months. The primary efficacy outcome was the percentage of SF reduction compared to the reference period and CG at 3 months. Secondary outcomes were SF and bilateral tonic-clonic seizure (BTCS) reduction, scale score changes, and correlations with 25(OH)D during the follow-up. RESULTS: Eighty-eight patients were enrolled in the study (56 females, aged 17-74 years), with median baseline SF per 3 months = 16.5 and ≥2 antiseizure medications in 88.6%. In 75 patients (85%), 25(OH)D was <30 ng/mL; 40 of them were randomly assigned to EG and 34 to CG. After the 3-month blinded period, SF reduction did not significantly differ between groups. However, during the open-label period, SF significantly decreased (30% median SF reduction, 33% responder rate at 12 months). BTCSs were reduced by 52%. M-FIS and QOLIE-31 scores were significantly improved at the whole group level. SF reduction correlated with 25(OH)D > 30 ng/mL for >6 months. SIGNIFICANCE: Despite no proven effect after the 3-month blinded period, the open-label study suggests that long-term vitamin D3 supplementation with optimal 25(OH)D may reduce SF and BTCSs, with a positive effect on fatigue and quality of life. These findings need to be confirmed by further long-term studies. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03475225 (03-22-2018).
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BACKGROUND: Decisions of withdrawal of life-sustaining therapy for patients with severe brain injury are often based on prognostic evaluations such as analysis of electroencephalography (EEG) reactivity (EEG-R). However, EEG-R usually relies on visual assessment, which requires neurophysiological expertise and is prone to inter-rater variability. We hypothesised that quantitative analysis of EEG-R obtained 3 days after patient admission can identify new markers of subsequent awakening and consciousness recovery. METHODS: In this prospective observational study of patients with severe brain injury requiring mechanical ventilation, quantitative EEG-R was assessed using standard 11-lead EEG with frequency-based (power spectral density) and functional connectivity-based (phase-lag index) analyses. Associations between awakening in the intensive care unit (ICU) and reactivity to auditory and nociceptive stimulations were assessed with logistic regression. Secondary outcomes included in-ICU mortality and 3-month Coma Recovery Scale-Revised (CRS-R) score. RESULTS: Of 116 patients, 86 (74%) awoke in the ICU. Among quantitative EEG-R markers, variation in phase-lag index connectivity in the delta frequency band after noise stimulation was associated with awakening (adjusted odds ratio=0.89, 95% confidence interval: 0.81-0.97, P=0.02 corrected for multiple tests), independently of age, baseline severity, and sedation. This new marker was independently associated with improved 3-month CRS-R (adjusted ß=-0.16, standard error 0.075, P=0.048), but not with mortality (adjusted odds ratio=1.08, 95% CI: 0.99-1.18, P=0.10). CONCLUSIONS: An early-stage quantitative EEG-R marker was independently associated with awakening and 3-month level of consciousness in patients with severe brain injury. This promising marker based on functional connectivity will need external validation before potential integration into a multimodal prognostic model.
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Lesiones Encefálicas , Estado de Conciencia , Humanos , Electroencefalografía , Pronóstico , Coma/diagnóstico , Coma/complicaciones , Lesiones Encefálicas/complicacionesRESUMEN
BACKGROUND: Quantitative electroencephalography (EEG) analysis offers the opportunity to study high-level cognitive processes across psychiatric disorders. In particular, EEG microstates translate the temporal dynamics of neuronal networks throughout the brain. Their alteration may reflect transdiagnostic anomalies in neurophysiological functions that are impaired in mood, psychosis, and autism spectrum disorders, such as sensorimotor integration, speech, sleep, and sense of self. The main questions this study aims to answer are as follows: 1) Are EEG microstate anomalies associated with clinical and functional prognosis, both in resting conditions and during sleep, across psychiatric disorders? 2) Are EEG microstate anomalies associated with differences in sensorimotor integration, speech, sense of self, and sleep? 3) Can the dynamic of EEG microstates be modulated by a non-drug intervention such as light hypnosis? METHODS: This prospective cohort will include a population of adolescents and young adults, aged 15 to 30 years old, with ultra-high-risk of psychosis (UHR), first-episode psychosis (FEP), schizophrenia (SCZ), autism spectrum disorder (ASD), and major depressive disorder (MDD), as well as healthy controls (CTRL) (N = 21 × 6), who will be assessed at baseline and after one year of follow-up. Participants will undergo deep phenotyping based on psychopathology, neuropsychological assessments, 64-channel EEG recordings, and biological sampling at the two timepoints. At baseline, the EEG recording will also be coupled to a sensorimotor task and a recording of the characteristics of their speech (prosody and turn-taking), a one-night polysomnography, a self-reference effect task in virtual reality (only in UHR, FEP, and CTRL). An interventional ancillary study will involve only healthy controls, in order to assess whether light hypnosis can modify the EEG microstate architecture in a direction opposite to what is seen in disease. DISCUSSION: This transdiagnostic longitudinal case-control study will provide a multimodal neurophysiological assessment of clinical dimensions (sensorimotor integration, speech, sleep, and sense of self) that are disrupted across mood, psychosis, and autism spectrum disorders. It will further test the relevance of EEG microstates as dimensional functional biomarkers. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT06045897.
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Trastorno del Espectro Autista , Trastorno Autístico , Trastorno Depresivo Mayor , Trastornos Psicóticos , Adulto Joven , Adolescente , Humanos , Adulto , Trastorno Autístico/diagnóstico , Trastorno del Espectro Autista/diagnóstico , Vigilia , Estudios de Casos y Controles , Depresión , Encéfalo , Sueño , Electroencefalografía/métodosRESUMEN
OBJECTIVES: Describe the prevalence of acute cerebral dysfunction and assess the prognostic value of an early clinical and electroencephalography (EEG) assessment in ICU COVID-19 patients. DESIGN: Prospective observational study. SETTING: Two tertiary critical care units in Paris, France, between April and December 2020. PATIENTS: Adult critically ill patients with COVID-19 acute respiratory distress syndrome. INTERVENTIONS: Neurologic examination and EEG at two time points during the ICU stay, first under sedation and second 4-7 days after sedation discontinuation. MEASUREMENTS AND MAIN RESULTS: Association of EEG abnormalities (background reactivity, continuity, dominant frequency, and presence of paroxystic discharges) with day-28 mortality and neurologic outcomes (coma and delirium recovery). Fifty-two patients were included, mostly male (81%), median (interquartile range) age 68 years (56-74 yr). Delayed awakening was present in 68% of patients (median awakening time of 5 d [2-16 d]) and delirium in 74% of patients who awoke from coma (62% of mixed delirium, median duration of 5 d [3-8 d]). First, EEG background was slowed in the theta-delta range in 48 (93%) patients, discontinuous in 25 patients (48%), and nonreactive in 17 patients (33%). Bifrontal slow waves were observed in 17 patients (33%). Early nonreactive EEG was associated with lower day-28 ventilator-free days (0 vs 16; p = 0.025), coma-free days (6 vs 22; p = 0.006), delirium-free days (0 vs 17; p = 0.006), and higher mortality (41% vs 11%; p = 0.027), whereas discontinuous background was associated with lower ventilator-free days (0 vs 17; p = 0.010), coma-free days (1 vs 22; p < 0.001), delirium-free days (0 vs 17; p = 0.001), and higher mortality (40% vs 4%; p = 0.001), independently of sedation and analgesia. CONCLUSIONS: Clinical and neurophysiologic cerebral dysfunction is frequent in COVID-19 ARDS patients. Early severe EEG abnormalities with nonreactive and/or discontinuous background activity are associated with delayed awakening, delirium, and day-28 mortality.
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Encefalopatías , COVID-19 , Delirio , Síndrome de Dificultad Respiratoria , Adulto , Anciano , Encéfalo , Encefalopatías/etiología , COVID-19/complicaciones , Coma/diagnóstico , Coma/etiología , Enfermedad Crítica , Delirio/diagnóstico , Delirio/epidemiología , Delirio/etiología , Femenino , Humanos , Unidades de Cuidados Intensivos , Masculino , Estudios Prospectivos , Respiración Artificial/efectos adversos , Síndrome de Dificultad Respiratoria/epidemiología , Síndrome de Dificultad Respiratoria/terapiaRESUMEN
Background and Purpose: In acute stroke, preventing infarct growth until complete recanalization occurs is a promising approach as an adjunct to reperfusion therapies to reduce infarct size and improve outcome. In rodent models, cathodal transcranial direct current stimulation (C-tDCS) decreases peri-infarct depolarizations and reduces infarct volume. We hypothesized that C-tDCS would nonpharmacologically reduce infarct growth in hyperacute middle cerebral artery territory stroke patients receiving reperfusion therapy. Methods: STICA (Cathodal Transcranial Direct Stimulation in Acute Middle Cerebral Artery Stroke) was a pilot single-center, double-blind, 2-arms 1:1 randomized trial evaluating the safety, feasibility, and efficacy of C-tDCS versus sham stimulation in patients eligible for recanalization therapies. Magnetic resonance imaging was obtained both on admission and 24 hours later. The primary end point was 24-hour infarct growth. Secondary outcomes were (1) National Institutes of Health Stroke Scale score difference between day 7 and admission and (2) 3-month modified Rankin Scale score. Results: Forty-five patients were randomized. Median magnetic resonance imaging-to-C-tDCS start time was 45 minutes; C-tDCS was started before completion of recanalization procedure in all patients. The intervention proved feasible in all patients. No major adverse effects occurred in either group. There was no significant difference between active and sham groups for any end point. However, an apparent trend towards smaller infarct growth in the C-tDCS arm was observed in the whole group (unadjusted median difference [IC95%]: −2.2 mL [−12.2 to 1.5]) and in the prespecified subsamples with moderate-to-severe stroke and large vessel occlusion (−5.7 mL [−21.6 to 2.6] and −7.7 mL [−24.2 to 2.6], respectively). Conclusions: C-tDCS was feasible and well tolerated. No significant difference was found between the active and sham groups. However, the data suggest potential benefits of C-tDCS in patients with National Institutes of Health Stroke Scale score of >10 or large vessel occlusion. Using the observed effect size and standard α=5% and ß=20%, samples of 102 and 86, respectively, can be estimated for future trials in patients with these characteristics. Randomized trials particularly targeting these populations may be warranted.
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Accidente Cerebrovascular Isquémico , Imagen por Resonancia Magnética , Estimulación Transcraneal de Corriente Directa , Enfermedad Aguda , Anciano , Anciano de 80 o más Años , Método Doble Ciego , Femenino , Humanos , Accidente Cerebrovascular Isquémico/diagnóstico por imagen , Accidente Cerebrovascular Isquémico/fisiopatología , Accidente Cerebrovascular Isquémico/terapia , Masculino , Persona de Mediana EdadRESUMEN
OBJECTIVES: We aimed to describe intracerebral aspects of postictal generalized electroencephalography suppression (PGES) following focal to bilateral tonic-clonic ("secondarily generalized tonic-clonic") seizures (GTCS) recorded using stereoelectroencephalographic (SEEG), and to correlate these with electroclinical features. METHODS: Three independent observers scored semiologic and SEEG features. Patient and epilepsy characteristics were collected. Descriptive statistics and multivariate analysis were performed. The operational definition of PGES on SEEG used strict criteria (absence of visible signal at 20 µV/mm amplitude, in all readable channels). Postictal regional suppression (RS) was identified if only a subset of implanted electrodes showed absence of signal. RESULTS: We evaluated 100 seizures in 52 patients. Interobserver agreement was good (κ 0.72 for clinical features and 0.73 for EEG features). PGES was present in 27 of 100 and RS without PGES present in 42 of 100 seizures. Region of RS included epileptogenic zone in 43 of 51 (86%). No effect of sampling (multilobar or bilateral exploration) was seen. Oral tonicity (mouth opening and/or tonic vocalization during the tonic phase of GTCS) was associated with the presence of PGES (P = 0.029; negative predictive value [NPV] 0.91). Bilateral upper limb extension during the tonic phase correlated with PGES (P = 0.041; NPV 0.85). Association of both oral tonicity and bilateral upper limb extension had a high NPV of 0.96. SIGNIFICANCE: SEEG recordings confirm true absence of signal during postictal EEG suppression. PGES is unlikely when both upper limb extension and oral tonicity are absent. We hypothesize that bilateral tonic seizure discharge at bulbar level brainstem regions is associated with the production of oral signs and may relate to mechanisms of PGES.
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Electroencefalografía/métodos , Epilepsias Parciales/diagnóstico , Epilepsias Parciales/fisiopatología , Convulsiones/diagnóstico , Convulsiones/fisiopatología , Técnicas Estereotáxicas , Adolescente , Adulto , Niño , Electrodos Implantados , Electroencefalografía/instrumentación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Técnicas Estereotáxicas/instrumentación , Adulto JovenRESUMEN
In light of technical advancements supporting exploration of MR signals other than 1H, sodium (23Na) has received attention as a marker of ionic homeostasis and cell viability. Here, we evaluate for the first time the possibility that 23Na-MRI is sensitive to pathological processes occurring in human epilepsy. A normative sample of 27 controls was used to normalize regions of interest (ROIs) from 1424 unique brain locales on quantitative 23Na-MRI and high-resolution 1H-MPRAGE images. ROIs were based on intracerebral electrodes in ten patients undergoing epileptic network mapping. The stereo-EEG gold standard was used to define regions as belonging to primarily epileptogenic, secondarily irritative and to non-involved regions. Estimates of total sodium concentration (TSC) on 23Na-MRI and cerebrospinal fluid (CSF) on 1H imaging were extracted for each patient ROI, and normalized against the same region in controls. ROIs with disproportionate CSF contributions (ZCSF≥1.96) were excluded. TSC levels were found to be elevated in patients relative to controls except in one patient, who suffered non-convulsive seizures during the scan, in whom we found reduced TSC levels. In the remaining patients, an ANOVA (F1100= 12.37, p<0.0001) revealed a highly significant effect of clinically-defined zones (F1100= 11.13, p<0.0001), with higher normalized TSC in the epileptogenic zone relative to both secondarily irritative (F1100= 11, p=0.0009) and non-involved regions (F1100= 17.8, p<0.0001). We provide the first non-invasive, in vivo evidence of a chronic TSC elevation alongside ZCSF levels within the normative range, associated with the epileptogenic region even during the interictal period in human epilepsy, and the possibility of reduced TSC levels due to seizure. In line with modified homeostatic mechanisms in epilepsy - including altered mechanisms underlying ionic gating, clearance and exchange - we provide the first indication of 23Na-MRI as an assay of altered sodium concentrations occurring in epilepsy associated with the organization of clinically relevant divisions of pathological cortex.
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Corteza Cerebral , Electrocorticografía/métodos , Epilepsia/diagnóstico por imagen , Epilepsia/metabolismo , Homeostasis/fisiología , Imagen por Resonancia Magnética/métodos , Sodio/metabolismo , Adulto , Corteza Cerebral/diagnóstico por imagen , Corteza Cerebral/metabolismo , Corteza Cerebral/fisiopatología , Epilepsia/fisiopatología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Protones , Sodio/líquido cefalorraquídeo , Adulto JovenRESUMEN
OBJECTIVE: To compare heart rate variability (HRV) parameters in newly diagnosed and untreated temporal lobe epilepsy (TLE) between the interictal, preictal, ictal, and postictal states. METHODS: HRV parameters were extracted from single-lead electrocardiography data collected during video-electroencephalography (EEG) recordings from 14 patients with newly diagnosed TLE in a resting, awake, and supine state. HRV parameters in the time and frequency domains included low frequency (LF), high frequency (HF), standard deviation of all consecutive R wave intervals (SDNN), and square root of the mean of the sum of the squares of differences between adjacent R wave intervals (RMSSD). Cardiovagal index (CVI), cardiosympathetic index (CSI), and approximate entropy (ApEn) were also studied. RESULTS: Frequency domain analysis showed significantly higher preictal, ictal, and postictal LF/HF ratio compared to the interictal state. Similarly, the LF component increased progressively and was significantly higher during the ictal state compared to interictal and preictal states. RR interval values were lower in the ictal state compared to basal and preictal states and in the postictal state compared to the preictal state. Interictal RMSSD was significantly higher compared to all other states, and ictal SDNN was significantly higher compared to all other states. Ictal CSI was significantly higher compared to preictal and interictal states, whereas preictal CVI was lower than in basal and ictal states. In addition, ictal ApEn was significantly lower than interictal and preictal ApEn. Interictal CVI was lower in left TLE compared to right TLE. In addition, in left TLE, ictal CVI was higher than interictal CVI, whereas in right TLE, CVI was lower in the preictal state compared to all other states. SIGNIFICANCE: Our data suggest an ictal sympathetic overdrive with partial recovery in the postictal state. Higher sympathetic tone and vagal tone imbalance may induce early autonomic dysfunction and increase cardiovascular risk in patients affected by TLE.
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Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/fisiopatología , Epilepsia del Lóbulo Temporal/diagnóstico , Epilepsia del Lóbulo Temporal/fisiopatología , Frecuencia Cardíaca , Adulto , Enfermedades del Sistema Nervioso Autónomo/diagnóstico , Enfermedades del Sistema Nervioso Autónomo/epidemiología , Enfermedades del Sistema Nervioso Autónomo/fisiopatología , Enfermedades Cardiovasculares/epidemiología , Electroencefalografía/métodos , Epilepsia del Lóbulo Temporal/epidemiología , Femenino , Frecuencia Cardíaca/fisiología , Humanos , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
Compared with temporal or frontal lobe epilepsies, the occipital lobe epilepsies (OLE) remain poorly characterized. In this study, we aimed at classifying the ictal networks involving OLE and investigated clinical features of the OLE network subtypes. We studied 194 seizures from 29 consecutive patients presenting with OLE and investigated by stereoelectroencephalography (SEEG). Epileptogenicity of occipital and extraoccipital regions was quantified according to the 'epileptogenicity index' (EI) method. We found that 79% of patients showed widespread epileptogenic zone organization, involving parietal or temporal regions in addition to the occipital lobe. Two main groups of epileptogenic zone organization within occipital lobe seizures were identified: a pure occipital group and an occipital "plus" group, the latter including two further subgroups, occipitotemporal and occipitoparietal. In 29% of patients, the epileptogenic zone was found to have a bilateral organization. The most epileptogenic structure was the fusiform gyrus (mean EI: 0.53). Surgery was proposed in 18/29 patients, leading to seizure freedom in 55% (Engel Class I). Results suggest that, in patient candidates for surgery, the majority of cases are characterized by complex organization of the EZ, corresponding to the occipital plus group.
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Electroencefalografía/métodos , Epilepsias Parciales/fisiopatología , Lóbulo Occipital/fisiopatología , Lóbulo Temporal/fisiopatología , Adolescente , Adulto , Niño , Epilepsias Parciales/cirugía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Procedimientos Neuroquirúrgicos/métodos , Lóbulo Occipital/cirugía , Lóbulo Temporal/cirugía , Resultado del Tratamiento , Adulto JovenRESUMEN
Apathy is a common clinical feature of stroke patients and it is often correlated with cognitive deficits, functional impairment and depression. Here we report the case of a 70-year-old woman with no history of neuropsychiatric disorders who showed abrupt onset of pure apathy after the onset of a right brain vascular lesion located in the head of the caudate nucleus, the anterior part of the putamen, and the genu and the anterior limb of the internal capsule. A complete neuropsychological and neurological examination did not show deficits. A comprehensive neuropsychiatric assessment focusing on the post-stroke hospitalization period showed severe motor, cognitive and affective apathy with no depression or other neuropsychiatric symptoms. This case highlights the key role of the dorsal striatum in the development of pure apathy, possibly due to its function in regulating approach-attachment behavior, affect and initiative, which are the emotional, cognitive and motor dimensions of apathy.
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Apatía , Hemorragias Intracraneales/psicología , Accidente Cerebrovascular/psicología , Anciano , Femenino , Humanos , Pruebas NeuropsicológicasRESUMEN
BACKGROUND: Electroencephalography (EEG) microstates translate resting-state temporal dynamics of neuronal networks throughout the brain and could constitute possible markers of psychiatric disorders. We tested the hypothesis of an increased imbalance between a predominant self-referential mode (microstate C) and a decreased attentional mode (microstate D) in psychosis, mood, and autism spectrum disorders. METHODS: We retrospectively included 135 subjects from an early psychosis outpatient unit, with available eyes-closed resting-state 19 electrodes EEG. Individual-level then group-level modified K-means clustering in controls provided four microstate maps that were then backfitted to all groups. Differences between microstate parameters (occurrence, coverage, and mean duration) were computed between controls and each group, and between disease groups. RESULTS: Microstate class D parameters were systematically decreased in disease groups compared with controls, with an effect size increasing along the psychosis spectrum, but also in autism. There was no difference in class C. C/D ratios of mean duration were increased only in SCZ compared with controls. CONCLUSIONS: The decrease in microstate class D may be a marker of stage of psychosis, but it is not specific to it and may rather reflect a shared dimension along the schizophrenia-autism spectrum. C/D microstate imbalance may be more specific to schizophrenia.
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Trastorno Autístico , Trastornos Psicóticos , Humanos , Trastorno Autístico/diagnóstico , Trastornos del Humor/diagnóstico , Estudios Retrospectivos , Trastornos Psicóticos/diagnóstico , Encéfalo/diagnóstico por imagen , Encéfalo/fisiología , Electroencefalografía/métodosRESUMEN
SUMMARY: The definition of consciousness has been the subject of great interest for many scientists and philosophers. To better understand how evoked potentials may be identified as biomarkers of consciousness and recovery, the different theoretical models sustaining neural correlates of consciousness are reviewed. A multimodal approach can help to better predict clinical outcome in patients presenting with disorders of consciousness. Evoked potentials are inexpensive and easy-to-implement bedside examination techniques. Evoked potentials are an integral part of prognostic evaluation, particularly in cases of cognitive motor dissociation. Prognostic criteria are well established in postanoxic disorders of consciousness, especially postcardiac arrest but are less well determined in other etiologies. In the early examination, bilateral absence of N20 in disorder of consciousness patients is strongly associated with unfavorable outcome (i.e., death or unresponsive wakefulness syndrome) especially in postanoxic etiologies. This predictive value is lower in other etiologies and probably also in children. Both N20 and mismatch negativity are proven outcome predictors for acute coma. Many studies have shown that mismatch negativity and P3a are characterized by a high prognostic value for awakening, but some patients presenting unresponsive wakefulness syndrome also process a P3a. The presence of long-latency event-related potential components in response to stimuli is indicative of a better recovery. All neurophysiological data must be integrated within a multimodal approach combining repeated clinical evaluation, neuroimaging, functional imaging, biology, and neurophysiology combining passive and active paradigms.
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Coma , Estado de Conciencia , Biomarcadores , Niño , Coma/diagnóstico , Trastornos de la Conciencia/diagnóstico , Electroencefalografía , Potenciales Evocados , Humanos , PronósticoRESUMEN
BACKGROUND: To assess in comatose patients after cardiac arrest (CA) if amplitudes of two somatosensory evoked potentials (SSEP) responses, namely, N20-baseline (N20-b) and N20-P25, are predictive of neurological outcome. METHODS: Monocentric prospective study in a tertiary cardiac center between Nov 2019 and July-2021. All patients comatose at 72 h after CA with at least one SSEP recorded were included. The N20-b and N20-P25 amplitudes were automatically measured in microvolts (µV), along with other recommended prognostic markers (status myoclonus, neuron-specific enolase levels at 2 and 3 days, and EEG pattern). We assessed the predictive value of SSEP for neurologic outcome using the best Cerebral Performance Categories (CPC1 or 2 as good outcome) at 3 months (main endpoint) and 6 months (secondary endpoint). Specificity and sensitivity of different thresholds of SSEP amplitudes, alone or in combination with other prognostic markers, were calculated. RESULTS: Among 82 patients, a poor outcome (CPC 3-5) was observed in 78% of patients at 3 months. The median time to SSEP recording was 3(2-4) days after CA, with a pattern "bilaterally absent" in 19 patients, "unilaterally present" in 4, and "bilaterally present" in 59 patients. The median N20-b amplitudes were different between patients with poor and good outcomes, i.e., 0.93 [0-2.05]µV vs. 1.56 [1.24-2.75]µV, respectively (p < 0.0001), as the median N20-P25 amplitudes (0.57 [0-1.43]µV in poor outcome vs. 2.64 [1.39-3.80]µV in good outcome patients p < 0.0001). An N20-b > 2 µV predicted good outcome with a specificity of 73% and a moderate sensitivity of 39%, although an N20-P25 > 3.2 µV was 93% specific and only 30% sensitive. A low voltage N20-b < 0.88 µV and N20-P25 < 1 µV predicted poor outcome with a high specificity (sp = 94% and 93%, respectively) and a moderate sensitivity (se = 50% and 66%). Association of "bilaterally absent or low voltage SSEP" patterns increased the sensitivity significantly as compared to "bilaterally absent" SSEP alone (se = 58 vs. 30%, p = 0.002) for prediction of poor outcome. CONCLUSION: In comatose patient after CA, both N20-b and N20-P25 amplitudes could predict both good and poor outcomes with high specificity but low to moderate sensitivity. Our results suggest that caution is needed regarding SSEP amplitudes in clinical routine, and that these indicators should be used in a multimodal approach for prognostication after cardiac arrest.
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OBJECTIVE: The acoustic characteristics of stimuli influence the characteristics of the corresponding evoked potentials in healthy subjects. Own-name stimuli are used in clinical practice to assess the level of consciousness in intensive care units. The influence of the acoustic variability of these stimuli has never been evaluated. Here, we explored the influence of this variability on the characteristics of the subject's own name (SON) P300. METHODS: We retrospectively analyzed 251 disorders of consciousness patients from Lyon and Paris Hospitals who underwent an "own-name protocol". A reverse correlation analysis was performed to test for an association between acoustic properties of own-names stimuli used and the characteristics of the P300 wave observed. RESULTS: Own-names pronounced with increasing pitch prosody showed P300 responses 66 ms earlier than own-names that had a decreasing prosody [IC95% = 6.36; 125.9 ms]. CONCLUSIONS: Speech prosody of the stimuli in the "own name protocol" is associated with latencies differences of the P300 response among patients for whom these responses were observed. Further investigations are needed to confirm these results. SIGNIFICANCE: Speech prosody of the stimuli in the "own name protocol" is a non-negligible parameter, associated with P300 latency differences. Speech prosody should be standardized in SON P300 studies.
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Coma/fisiopatología , Electroencefalografía/métodos , Potenciales Relacionados con Evento P300 , Percepción del Habla , Coma/diagnóstico , Electroencefalografía/normas , Femenino , Humanos , Masculino , Semántica , Acústica del LenguajeRESUMEN
Objective: To investigate the electroclinical characteristics and the prognostic impact of generalized fast discharges in a large cohort of genetic generalized epilepsy (GGE) patients studied with 24-h prolonged ambulatory electroencephalography (paEEG). Methods: This retrospective multicenter cohort study included 202 GGE patients. The occurrence of generalized paroxysmal fast activity (GPFA) and generalized polyspike train (GPT) was reviewed. GGE patients were classified as having idiopathic generalized epilepsy (IGE) or another GGE syndrome (namely perioral myoclonia with absences, eyelid myoclonia with absences, epilepsy with myoclonic absences, generalized epilepsy with febrile seizures plus, or GGE without a specific epilepsy syndrome) according to recent classification proposals. Results: GPFA/GPT was found in overall 25 (12.4%) patients, though it was significantly less frequent in IGE compared with other GGE syndromes (9.3 vs. 25%, p = 0.007). GPFA/GPT was found independently of seizure type experienced during history, the presence of mild intellectual disability/borderline intellectual functioning, or EEG features. At multivariable analysis, GPFA/GPT was significantly associated with drug resistance (p = 0.04) and with a higher number of antiseizure medications (ASMs) at the time of paEEG (p < 0.001) and at the last medical observation (p < 0.001). Similarly, GPFA/GPT, frequent/abundant generalized spike-wave discharges during sleep, and a higher number of seizure types during history were the only factors independently associated with a lower chance of achieving 2-year seizure remission at the last medical observation. Additionally, a greater number of GPFA/GPT discharges significantly discriminated between patients who achieved 2-year seizure remission at the last medical observation and those who did not (area under the curve = 0.77, 95% confidence interval 0.57-0.97, p = 0.02). Conclusion: We found that generalized fast discharges were more common than expected in GGE patients when considering the entire GGE spectrum. In addition, our study highlighted that GPFA/GPT could be found along the entire GGE continuum, though their occurrence was more common in less benign GGE syndromes. Finally, we confirmed that GPFA/GPT was associated with difficult-to-treat GGE, as evidenced by the multivariable analysis and the higher ASM load during history.
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Objective. To measure the impact of skull-to-brain conductivity ratios on interictal spikes source localizations, using high resolution EEG (HR EEG). In previous studies, two ratios were mainly employed: 1/80 and 1/40. Consequences of the employed ratios on source localization results are poorly studied.Methods. Twenty patients with drug-resistant epilepsy were studied using HR EEG (sixty-four scalp electrodes). For each patient, three-layers realistic head models based on individual MRI were elaborated using boundary element model. For each interictal spike, source localization was performed six times, using six skull-to-brain conductivity ratios (1/80, 1/50, 1/40, 1/30, 1/20 and 1/10), exploring all the spectrum of values reported in the literature. We then measured distances between the different sources obtained and between the sources and the anterior commissure (in order to estimate sources depth).Results. We measured a mean distance of 5.3 mm (sd: 3 mm) between the sources obtained with 1/40 versus 1/80 ratio. This distance increased when the discrepancy between the two evaluated ratios increased. We measured a mean distance of 14.2 mm (sd: 4.9 mm) between sources obtained with 1/10 ratio versus 1/80 ratio. Sources localized using 1/40 ratio were 4.3 mm closer to the anterior commissure than sources localized using 1/80 ratio.Significance. Skull-to-brain conductivity ratio is an often-neglected parameter in source localization studies. The different ratios mainly used in the litterature (1/80 and 1/40) lead to significant differences in source localizations. These variations mainly occur in source depth. A more accurate estimation of skull-to-brain conductivity is needed to increase source localization accuracy.Abbreviations. ECD: equivalent current dipole; EIT: electric impedance tomography, HR EEG: High resolution Electroencephalography, IIS: Inter ictal spikes, MEG: Magnetoencephalography, MRI: Magnetic resonance imaging, mS/m: milli-Siemens/m, S/m: Siemens/m, SD: Standard deviation.
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Electroencefalografía , Cráneo , Encéfalo/diagnóstico por imagen , Humanos , Magnetoencefalografía , Cuero Cabelludo , Cráneo/diagnóstico por imagenRESUMEN
Introduction: VNS is an adjunctive neuromodulation therapy for patients with drug-refractory epilepsy. The antiseizure effect of VNS is thought to be related to a diffuse modulation of functional connectivity but remains to be confirmed. Aim: To investigate electroencephalographic (EEG) metrics of functional connectivity in patients with drug-refractory epilepsy treated by vagus nerve stimulation (VNS), between VNS-stimulated "ON" and nonstimulated "OFF" periods and between responder (R) and nonresponder (NR) patients. Methods: Scalp-EEG was performed for 35 patients treated by VNS, using 21 channels and 2 additional electrodes on the neck to detect the VNS stimulation. Patients were defined as VNS responders if a reduction of seizure frequency of â¼50% was documented. We analyzed the synchronization in EEG time series during "ON" and "OFF" periods of stimulation, using average phase lag index (PLI) in signal space and phase-locking value (PLV) between 10 sources. Based on graph theory, we computed brain network models and analyzed minimum spanning tree (MST) for responder and nonresponder patients. Results: Among 35 patients treated by VNS for a median time of 7 years (range 4 months to 22 years), 20 were R and 15 were NR. For responder patients, PLI during ON periods was significantly lower than that during OFF periods in delta (p = 0.009), theta (p = 0.02), and beta (p = 0.04) frequency bands. For nonresponder patients, there were no significant differences between ON and OFF periods. Moreover, variations of seizure frequency with VNS correlated with the PLI OFF/ON ratio in delta (p = 0.02), theta (p = 0.04), and beta (p = 0.03) frequency bands. Our results were confirmed using PLV in theta band (p < 0.05). No significant differences in MST were observed between R and NR patients. Conclusion: The correlation between VNS-induced interictal EEG time-series desynchronization and decrease in seizure frequency suggested that VNS therapeutic impact might be related to changes in interictal functional connectivity. Impact statement Electroencephalography (EEG) desynchronization has been proposed to be a mechanism for antiepileptic effect of vagus nerve stimulation (VNS). We measured interictal EEG time-series synchronization during stimulated (ON) and nonstimulated (OFF) periods in epileptic patients treated by VNS. Phase lag index differences between ON and OFF periods were measured in delta, theta, and beta bands only in responder patients. To our knowledge, our study is the first to statistically correlate interictal cortical desynchronization during ON periods with reduction in seizure frequency. Our result supports the hypothesis that the antiseizure effect of VNS is mediated by cortical desynchronization.
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Encéfalo/fisiopatología , Sincronización Cortical/fisiología , Epilepsia Refractaria/terapia , Estimulación del Nervio Vago , Adulto , Epilepsia Refractaria/fisiopatología , Electroencefalografía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
Stroke constitutes the third most common cause of death and the leading cause of acquired neurologic handicap. During ischemic stroke, very early after the onset of the focal perfusion deficit, excitotoxicity triggers a number of events that can further contribute to tissue death. Such events include peri-infarct depolarizations and spreading depolarizations (SDs) within the ischemic penumbra. SDs spread slowly through continuous gray matter at a typical velocity of 2-5mm/min. SDs exacerbate neuronal injury through prolonged ionic breakdown and SD-related hypoperfusion (spreading ischemia). Scalp EEG alone is not yet sufficient to reliably diagnose SDs. Hyperexcitability occurs in parallel, both in the acute and chronic phases of stroke. Stroke is a common cause of new-onset epileptic seizures after middle age and is the leading cause of symptomatic epilepsy in adults. The last part of this chapter is dedicated to noninvasive neurophysiologic techniques that can be used to promote stroke rehabilitation. These techniques mainly include repetitive transcranial magnetic stimulation and tDCS. These approaches are based on the concept of interhemispheric rivalry and aim at modulating the imbalance of cortical activities between both hemispheres resulting from stroke.
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Accidente Cerebrovascular/fisiopatología , Animales , Humanos , Rehabilitación de Accidente Cerebrovascular/métodosRESUMEN
OBJECTIVE Post-stroke epilepsy (PSE) represents a rare etiology in patients undergoing pre-surgical evaluation for epilepsy. Refractory PSE has been traditionally surgically treated with hemispherotomy. The aim of this study was to define the electrophysiological features of epileptogenic zone (EZ) using stereoelectroencephalography (SEEG) recordings in patients with refractory PSE. METHODS We analyzed ictal SEEG recordings from 21 consecutive patients. Epileptogenicity was quantified using the "epileptogenicity index" (EI) method in distant and perilesional cortical structures. We identified different seizure onset patterns (SOP) through a visual and time-frequency analysis. RESULTS We found that 81% of patients showed a complex organization of EZ, involving remote and perilesional structures. EZ involved a significantly (pâ¯<â¯0.01) higher number of distant regions displaying a high epileptogenicity (EIâ¯≥â¯0.3). Low voltage fast activity (LFA) and high amplitude slow activity (HAS) patterns were observed respectively in 85.7% and 14.3% of patients. Surgery was proposed in 12/21 patients. Good surgical outcome (Engel Class I or II) was observed for all patients who underwent tailored functional disconnection based on SEEG results. Shorter epilepsy duration to surgery was found in the seizure-free group. SIGNIFICANCE Refractory PSE may present a complex organization of EZ. SEEG recordings are warranted to guide tailored hemispherectomy.
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Encéfalo/cirugía , Epilepsia Refractaria/cirugía , Hemisferectomía/métodos , Convulsiones/cirugía , Adolescente , Adulto , Encéfalo/fisiopatología , Epilepsia Refractaria/fisiopatología , Electroencefalografía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Convulsiones/fisiopatología , Resultado del Tratamiento , Adulto JovenRESUMEN
Instrumentation, control and automation (ICA) are currently applied throughout the urban water system at water treatment plants, in water distribution networks, in sewer networks, and at wastewater treatment plants. However, researchers and practitioners specialising in respective urban water sub-systems do not frequently interact, and in most cases to date the application of ICA has been achieved in silo. Here, we review start-of-the-art ICA throughout these sub-systems, and discuss the benefits achieved in terms of performance improvement, cost reduction, and more importantly, the enhanced capacity of the existing infrastructure to cope with increased service demand caused by population growth and continued urbanisation. We emphasise the importance of integrated control within each of the sub-systems, and also across the entire urban water system. System-wide ICA will have increasing importance with the growing complexity of the urban water environment in cities of the future.