Postictal Generalized EEG Suppression Research Articles

Dynamics of convulsive seizure termination and postictal generalized EEG suppression.

It is not fully understood how seizures terminate and why some seizures are followed by a period of complete brain activity suppression, postictal generalized EEG suppression. This is clinically relevant as there is a potential association between postictal generalized EEG suppression, cardiorespiratory arrest and sudden death following a seizure. We combined human encephalographic seizure data with data of a computational model of seizures to elucidate the neuronal network dynamics underlying seizure termination and the postictal generalized EEG suppression state. A multi-unit computational neural mass model of epileptic seizure termination and postictal recovery was developed. The model provided three predictions that were validated in EEG recordings of 48 convulsive seizures from 48 subjects with refractory focal epilepsy (20 females, age range 15-61 years). The duration of ictal and postictal generalized EEG suppression periods in human EEG followed a gamma probability distribution indicative of a deterministic process (shape parameter 2.6 and 1.5, respectively) as predicted by the model. In the model and in humans, the time between two clonic bursts increased exponentially from the start of the clonic phase of the seizure. The terminal interclonic interval, calculated using the projected terminal value of the log-linear fit of the clonic frequency decrease was correlated with the presence and duration of postictal suppression. The projected terminal interclonic interval explained 41% of the variation in postictal generalized EEG suppression duration (P < 0.02). Conversely, postictal generalized EEG suppression duration explained 34% of the variation in the last interclonic interval duration. Our findings suggest that postictal generalized EEG suppression is a separate brain state and that seizure termination is a plastic and autonomous process, reflected in increased duration of interclonic intervals that determine the duration of postictal generalized EEG suppression.

Efficacy of naloxone in reducing postictal central respiratory dysfunction in patients with epilepsy: study protocol for a double-blind, randomized, placebo-controlled trial.

BackgroundGeneralized tonic-clonic seizures (GTCSs) are the main risk factor for sudden unexpected death in epilepsy (SUDEP). Experimental and clinical data strongly suggest that the majority of SUDEP results from a postictal respiratory dysfunction progressing to terminal apnea. Postictal apnea could partly derive from a seizure-induced massive release of endogenous opioids. The main objective of this study is to evaluate the efficacy of an opioid antagonist, naloxone, administered in the immediate aftermath of a GTCS, in reducing the severity of the postictal central respiratory dysfunction.Methods/designThe Efficacy of Naloxone in Reducing Postictal Central Respiratory Dysfunction in Patients with Epilepsy (ENALEPSY) study is a multicenter, double-blind, randomized, placebo-controlled trial conducted in patients with drug-resistant focal epilepsy who are undergoing long-term video-electroencephalogram (EEG) monitoring (LTM) in an epilepsy monitoring unit (EMU). We plan to randomize 166 patients (1:1) to receive intravenous naloxone (0.4 mg) or placebo in the immediate aftermath of a GTCS. Because inclusion in the study needs to take place prior to the occurrence of the GTCS, and because such occurrence is observed in about one-fourth of patients undergoing LTM, we plan to include a maximum of 700 patients upon admission in the EMU. The primary endpoint will be the proportion of patients whose oxygen saturation is <90 % between 1 and 3 min after the end of a GTCS. Secondary outcomes will include the following: the proportion of patients who show postictal apnea, the occurrence and duration of postictal generalized EEG suppression, the total duration of the postictal coma, postictal pain, and the number of patients who have a second GTCS within 120 min after the intravenous injection.DiscussionThe demonstration of naloxone’s efficacy on the severity of postictal hypoxemia will have two primary consequences. First, naloxone would be the first and only therapeutic approach that could be delivered immediately to reverse postictal apnea. Second, demonstration that an opioid antagonist can effectively reduce postictal apnea would pave the way for an assessment of a preventive therapy for SUDEP targeting the same pathophysiological pathway using oral administration of naltrexone.Trial registrationClinicalTrials.gov identifier: NCT02332447. Registered on 5 January 2015.Electronic supplementary materialThe online version of this article (doi:10.1186/s13063-016-1653-1) contains supplementary material, which is available to authorized users.

Automated Video Detection of Epileptic Convulsion Slowing as a Precursor for Post-Seizure Neuronal Collapse.

Automated monitoring and alerting for adverse events in people with epilepsy can provide higher security and quality of life for those who suffer from this debilitating condition. Recently, we found a relation between clonic slowing at the end of a convulsive seizure (CS) and the occurrence and duration of a subsequent period of postictal generalized EEG suppression (PGES). Prolonged periods of PGES can be predicted by the amount of progressive increase of interclonic intervals (ICIs) during the seizure. The purpose of the present study is to develop an automated, remote video sensing-based algorithm for real-time detection of significant clonic slowing that can be used to alert for PGES. This may help preventing sudden unexpected death in epilepsy (SUDEP). The technique is based on our previously published optical flow video sequence processing paradigm that was applied for automated detection of major motor seizures. Here, we introduce an integral Radon-like transformation on the time-frequency wavelet spectrum to detect log-linear frequency changes during the seizure. We validate the automated detection and quantification of the ICI increase by comparison to the results from manually processed electroencephalography (EEG) traces as "gold standard". We studied 48 cases of convulsive seizures for which synchronized EEG-video recordings were available. In most cases, the spectral ridges obtained from Gabor-wavelet transformations of the optical flow group velocities were in close proximity to the ICI traces detected manually from EEG data during the seizure. The quantification of the slowing-down effect measured by the dominant angle in the Radon transformed spectrum was significantly correlated with the exponential ICI increase factors obtained from manual detection. If this effect is validated as a reliable precursor of PGES periods that lead to or increase the probability of SUDEP, the proposed method would provide an efficient alerting device.

Local brain activity persists during apparently generalized postictal EEG suppression.

Postictal generalized EEG suppression (PGES) frequently occurs after generalized convulsive seizures (GCS) and may be involved in the pathophysiology of sudden unexpected death in epilepsy (SUDEP). It is usually determined using conventional scalp EEG which is likely to miss cerebral activity in deeper brain structures. Here, we examined intracranial EEG activity after GCS to unravel the pattern and extent of local brain activity during apparent PGES on scalp EEG (s-PGES). We retrospectively reviewed electroencephalographic data of people with chronic epilepsy who had GCS during presurgical video-EEG monitoring using simultaneous intracranial and scalp EEG (10-20 system) electrodes. Twenty-five GCS (20 with s-PGES) of 15 patients with an average number of 88±42 intracranial electrode contacts were included. The majority of GCS with s-PGES (18 of 20) displayed persisting or reemerging intracranial EEG activity during apparent PGES on scalp EEG. Three patterns were identified: Pattern 1 (11 GCS, 6 patients) consisted of continuous local interictal activity; Pattern 2 (5 GCS, 5 patients) displayed suppressed EEG activity at all intracranial contacts in the early phase of s-PGES, but reemerging local brain activity before s-PGES dissolved; and Pattern 3 (2 GCS, 2 patients) showed persistent local ictal activity during s-PGES. Persisting intracranial EEG activity at PGES onset on scalp EEG was present in 10±14% (range: 0 to 42%) of all intracranial contacts and mostly in the temporal lobe. Our results reveal that, during apparently generalized postictal EEG suppression, local brain activity persists or reemerges in most GCS. Possible implications of this localized neuronal activity in the context of SUDEP are discussed in the paper.

The SUDEP Risk Inventory: Association with Postictal Generalized EEG Suppression (P6.362)

The SUDEP Risk Inventory: Association with Postictal Generalized EEG Suppression (P6.362)

Impact of periictal nurse interventions on postictal generalized EEG suppression in generalized convulsive seizures.

The objective of this study was to determine the impact of periictal nurse interventions on postictal generalized EEG suppression (PGES) in generalized convulsive seizures (GCS). We retrospectively reviewed the video-EEG recordings of patients during long-term video-EEG monitoring. We compared the duration of seizures, seizure phases (tonic, clonic, and tonic-clonic phases), and the occurrence and duration of postictal generalized EEG suppression (PGES) in patients with and without periictal interventions (e.g., oxygen administration, suctioning, and repositioning). Statistical analyses were performed to determine the association between the seizure-related variables and the periictal interventions. A total of 109 patients with 150 GCS were included in the study. Periictal interventions were provided in 122 GCS, of which, ictal administration of oxygen was provided in 29 GCS. The duration of PGES was significantly shortened in GCS with interventions when compared with those without interventions (p=0.003). However, the ictal administration of oxygen, assessed as an independent variable, did not influence the occurrence or duration of PGES. Periictal interventions significantly shortened the duration of PGES, and may, as a consequence, reduce the risk of SUDEP. However, ictal administration of oxygen did not influence the occurrence or duration of PGES.

Generalized Convulsive Seizure Type, Oxygen Administration, Postictal Generalized EEG Suppression, and SUDEP Risk: Are They Related?

Generalized Convulsive Seizure Type, Oxygen Administration, Postictal Generalized EEG Suppression, and SUDEP Risk: Are They Related?

Postictal generalized EEG suppression after generalized convulsive seizures: A double-edged sword.

The aim of this study is to investigate the key facilitating factors for postictal generalized EEG suppression (PGES) in a large cohort of patients with generalized convulsive seizures (GCSs). We retrospectively reviewed the data of consecutive patients who had GCSs in the epilepsy monitoring units of two epilepsy centers. Statistical analysis was performed to assess specific variables as potential risk factors for PGES. Among the 208 enrolled patients with 366 seizures, PGES was observed in 109 (51.9%) patients and 168 (45.9%) GCSs. The mean duration of PGES was 33.2 ± 12.0 s (34 s, 3-70 s). PGES or severe PGES (>20 s) was associated with more severe postictal coma and temporal lobe epilepsy. Moreover, PGES was independently associated with a longer tonic duration, shorter total seizure duration, and lower habitual seizure frequency. PGES is strongly correlated not only with longer tonic duration, but also with shorter total seizure duration and lower habitual seizure frequency. PGES may represent a switch-off inhibitory mechanism in seizure termination; moreover, it may indicate the efficacy of a long-lasting inhibitory network that suppresses GCS ictogenesis.

Spotlight on the November 3 Issue

#### Notable in Neurology This issue features an article using serial diffusion tensor imaging to show that cerebral tubers are neither static nor discrete and another article discussing the clinical and genetic analyses of 110 patients with paroxysmal kinesigenic dyskinesia. Another featured article focuses on the risk factors of postictal generalized EEG suppression in generalized convulsive seizures. ### Survival in synucleinopathies: A prospective cohort study This study compared survival in synucleinopathies involving orthostatic hypotension (OH), including Parkinson disease (PD) and multiple system atrophy (MSA). …

The SUDEP Risk Inventory: Association with postictal generalized EEG suppression

To help identify patients at greatest risk for sudden unexpected death in epilepsy (SUDEP), screening inventories like the SUDEP-7 Inventory can be useful. In this study, we examined the strength of association between this inventory's risk factors and postictal generalized EEG suppression (PGES), a biomarker of SUDEP risk. We reanalyzed data from an epilepsy monitoring unit study of 37 children. We performed a 2 by 2 contingency table analysis to determine the association between “yes” responses on the inventory questions and PGES following >=1 seizure. Having a history of >3 generalized tonic–clonic seizures (GTCS) in the past year had the strongest association with PGES (Pearson chi-square p<0.001, Cramer's V=0.75). Having >=1 GTCS in the past year was also strongly associated with PGES (Pearson chi-square p<0.001, Cramer's V=0.636). Histories of >50 seizures of any type/month (Pearson chi-square p=0.14, Cramer's V=0.241) and intellectual disability (Pearson chi-square p=0.04, Cramer's V=0.337) were not as robustly associated with PGES. Current use of >=3 AEDs had the weakest association with PGES (Pearson chi-square p=0.66, Cramer's V=0.072). Given that all study patients had >=1 seizure per year and epilepsy durations <30 years, the strength of association with these questions and PGES could not be analyzed.

Risk factors of postictal generalized EEG suppression in generalized convulsive seizures.

To identify the clinical determinants of occurrence of postictal generalized EEG suppression (PGES) after generalized convulsive seizures (GCS). We reviewed the video-EEG recordings of 417 patients included in the REPO2MSE study, a multicenter prospective cohort study of patients with drug-resistant focal epilepsy. According to ictal semiology, we classified GCS into 3 types: tonic-clonic GCS with bilateral and symmetric tonic arm extension (type 1), clonic GCS without tonic arm extension or flexion (type 2), and GCS with unilateral or asymmetric tonic arm extension or flexion (type 3). Association between PGES and person-specific or seizure-specific variables was analyzed after correction for individual effects and the varying number of seizures. A total of 99 GCS in 69 patients were included. Occurrence of PGES was independently associated with GCS type (p < 0.001) and lack of early administration of oxygen (p < 0.001). Odds ratio (OR) for GCS type 1 in comparison with GCS type 2 was 66.0 (95% confidence interval [CI 5.4-801.6]). In GCS type 1, risk of PGES was significantly increased when the seizure occurred during sleep (OR 5.0, 95% CI 1.2-20.9) and when oxygen was not administered early (OR 13.4, 95% CI 3.2-55.9). The risk of PGES dramatically varied as a function of GCS semiologic characteristics. Whatever the type of GCS, occurrence of PGES was prevented by early administration of oxygen.

Autonomic changes following generalized tonic clonic seizures: An analysis of adult and pediatric patients with epilepsy

ObjectiveSudden unexpected death in epilepsy (SUDEP) is the most common cause of mortality directly related to epilepsy. Its incidence is higher in adult patients and its pathophysiology remains poorly understood, but likely involves autonomic dysregulation following generalized tonic clonic seizures (GTCS). In the current study, we aimed to analyze post-ictal autonomic changes following GTCS in adult and pediatric patients. MethodsPatients admitted to the epilepsy monitoring unit were prospectively recruited, and wore an electrodermal activity (EDA) wrist sensor that continuously measured sympathetic activity while being monitored with EEG and EKG electrodes. Peri-ictal EDA parameters were assessed as a measure of sympathetic activity. Peri-ictal parasympathetic activity was determined through the high frequency component (HF) analysis of heart rate variability (HRV). The duration of post-ictal generalized EEG suppression (PGES) was also documented. ResultsTwenty patients with GTCS were included in the study on whom 30 GTCS were recorded. PGES duration strongly correlated with age (r=0.62, p=0.004) and measures of the EDA response. After controlling for PGES duration, we found pediatric patients had greater sympathetic activation measured as log rising portion of the area under the curve of the EDA response (β=+0.67, p=0.034) and a higher degree of vagal suppression measured as maximal percentage change of HF power (β=−12.65, p=0.0036). ConclusionSympathetic activity can be measured in the peri-ictal period, and directly correlates with PGES duration. Age is a significant determinant of the sympathetic and parasympathetic response following a GTCS; given the same PGES duration, pediatric patients demonstrate stronger sympathetic activation and higher vagal suppression. However, the increase in PGES duration with age and the associated autonomic dysregulation may provide clues as to why there is a variable vulnerability to SUDEP across age groups.

Antiepileptic action of c-Jun N-terminal kinase (JNK) inhibition

tonic–clonic seizures (GTCSs) and 19 out of 22 (86%) complex partial seizures (CPS) were accompanied by significant increases in EDA, more than 2 standard deviations above the preictal baseline [2]. While responses for GTCSs are usually higher than those for CPS, the size of the EDA response was not associatedwith the length of the seizure nor was it associated with the duration of the motor component in GTCSs [2]. Combining EDA data with motion data improved the accuracy of automated GTCS detection [3]. We have examined the relationship between EDA response during GTCSs and postictal generalized EEG suppression (PGES). The duration of PGES is a potential biomarker of SUDEP. Postictal generalized EEG suppression was found in all monitored cases of SUDEP in the MORTEMUS study [4]. Our studies in a pediatric population with treatment-resistant epilepsy showed that longer PGES correlates with larger EDA response during GTCSs [2]. This finding was replicated in a larger cohort, including children and adults, at another hospital [5]. Thus, EDA on the wrist provides a strong correlate to PGES duration. Altered autonomic function is considered by many to be among the mechanisms that lead to SUDEP [6]. In addition to the EDAfindings, our studies showed decreased heart rate variability associated with longer duration of PGES, which is also consistent with autonomic disruption. Respiratory arrest is inducible in humans by electrical stimulation of the amygdala during the expiratory phase of the respiratory cycle [7]. Stimulation of the amygdala in patients with epilepsy can produce a very strong ipsilateral EDA response [1]. We encourage more clinical studies to collect and examine autonomic data in epilepsy, especially since it can nowbe easily collected.

Pulmonary edema following generalized tonic clonic seizures is directly associated with seizure duration

PurposePostictal pulmonary edema (PPE) is almost invariably present in human and animal cases of sudden unexpected death in epilepsy (SUDEP) coming to autopsy. PPE may be a contributing factor in SUDEP. The incidence of postictal PPE is unknown. We retrospectively investigated PPE following generalized tonic clonic seizures (GTCS) in the epilepsy monitoring unit. MethodChest X-rays (CXR) following each GTCS were obtained in 24 consecutive patients. Relationship of CXR abnormality to seizure duration, ictal/postictal oxygen desaturation (SpO2), apnea and presence of postictal generalized EEG suppression (PGES) was investigated using logistic regression. ResultsEleven of 24 patients had CXR abnormalities following a GTCS. In these 11 patients, 22 CXR were obtained and abnormalities were present in 15 CXR. Abnormalities included PPE in 7 patients, of which 2 also had focal infiltrates. In 4 patients focal infiltrates were present without PPE. There was no significant difference in mean time to CXR (225min) following GTCS in the abnormal CXR group versus the normal group of patients (196min).Mean preceding seizure duration was longer (p=0.002) in GTCS with abnormal CXR (259.7s) versus GTCS with normal CXR (101.2s). Odds-ratio for CXR abnormality was 20.46 (p=0.006) with seizure duration greater than 100s versus less than 100s. On multivariable analysis, only the seizure duration was a significant predictor of CXR abnormality (p=0.015). ConclusionRadiographic abnormalities are not uncommon following GTCS. The presence of CXR abnormality is significantly associated with the duration of the preceding GTCS. Severe, untreated PPE may be relevant to the pathophysiology of SUDEP.

Postictal generalized EEG suppression and SUDEP: a review.

Sudden unexpected death in epilepsy (SUDEP) remains a leading cause of epilepsy-related death, and yet, its pathogenic mechanisms remain ill-defined. Although epidemiological studies of SUDEP in heterogenous populations have established a number of clinical associations, evaluation and stratification of individual risk remains difficult. Thus, potential markers as predictors of risk of SUDEP are important not only clinically but also for research on SUDEP prevention. Recordings from rare monitored cases of SUDEP demonstrate postictal generalized EEG suppression after terminal seizures, raising expectations that postictal generalized EEG suppression may identify individuals at higher risk. In this review, we consider the literature on postictal generalized EEG suppression and evaluate its relevance and utility as a possible marker of SUDEP.

Seizure-related autonomic changes in children.

Although sudden unexpected death in epilepsy is encountered less frequently in children versus adults, it is still an important direct epilepsy-related cause of death in this population. Just as in adults, the pathophysiology of sudden unexpected death in epilepsy in children is believed to involve seizure-related autonomic dysfunction. Seizures that develop during the pediatric period can be marked by some of the most dramatic alterations in autonomic functions seen at any age. This article reviews such seizure-related autonomic changes, including ictal nausea/emesis, hypersalivation, hypoxemia, apnea, tachycardia, bradycardia, cardiac repolarization anomalies, reduced heart rate variability, and postictal generalized EEG suppression. Understanding age-related changes in the autonomic effects of seizures and how they relate to risk of sudden death may help us to one day better elucidate the pathophysiology of sudden unexpected death in epilepsy. Given the high rate of sudden unexpected death in epilepsy in certain pediatric populations (such as those with Dravet syndrome), this knowledge is desperately needed.

P459: Electro-clinical features of focal epilepsy patients with postictal generalized EEG suppression

P459: Electro-clinical features of focal epilepsy patients with postictal generalized EEG suppression

P96: Age-specific characteristics of seizures, ictal encephalographic (EEG) pattern and postictal generalized EEG suppression in Dravet syndrome

P96: Age-specific characteristics of seizures, ictal encephalographic (EEG) pattern and postictal generalized EEG suppression in Dravet syndrome

Heart rate variability analysis indicates preictal parasympathetic overdrive preceding seizure‐induced cardiac dysrhythmias leading to sudden unexpected death in a patient with epilepsy

Evidence for seizure-induced cardiac dysrhythmia leading to sudden unexpected death in epilepsy (SUDEP) has been elusive. We present a patient with focal cortical dysplasia who has had epilepsy for 19 years and was undergoing presurgical evaluation. The patient did not have any cardiologic antecedents. During long-term video-electroencephalography (EEG) monitoring, following a cluster of secondarily generalized tonic-clonic seizures (GTCS), the patient had prolonged postictal generalized EEG suppression, asystole, followed by arrhythmia, and the patient died despite cardiopulmonary resuscitation. Analysis of heart rate variability showed a marked increase in the parasympathetic activity during the period preceding the fatal seizures, compared with values measured 1 day and 7 months before, and also higher than the preictal values in a group of 10 patients with GTCS without SUDEP. The duration of the QTc interval was short (335-358 msec). This unfortunate case documented during video-EEG monitoring indicates that autonomic imbalance and seizure-induced cardiac dysrhythmias contribute to the pathomechanisms leading to SUDEP in patients at risk (short QT interval).

Comparison of cardiorespiratory and EEG abnormalities with seizures in adults and children

Cardiopulmonary dysfunction and postictal generalized EEG suppression (PGES) are proposed as possible risk factors for the occurrence of SUDEP. The evolution of cardiorespiratory abnormalities with seizures has not been systematically studied for any age-related findings. Additionally, not many studies have looked into the possible effect of age-related brain maturation on PGES. The purpose of this study was to compare these SUDEP risk factors in adults versus children. We prospectively recorded cardiopulmonary abnormalities during seizures using pulse oximetry, EKG, and respiratory inductance plethysmography. Linear and logistic regression models adjusting for multiple seizures in a single patient were used to compare the cardiorespiratory and EEG findings between adults and children. We recorded 101 seizures in 26 children and 55 seizures in 22 adults. Ictal central apnea and bradycardia occurred more often in children than in adults (p=0.02 and p=0.008, respectively), while ictal tachycardia occurred more often in adults (p=0.001) than in children. Postictal generalized EEG suppression of longer duration occurred more often in adults (p=0.003) than in children. Minimum O2 saturation and seizure duration/generalization/lateralization did not significantly differ between adults and children (p>0.1). Children had more frontal lobe seizures, and adults had more temporal lobe seizures recorded (p=0.01). There may be an age-related effect on cardiorespiratory and EEG abnormalities associated with seizures, with higher rates of apnea and bradycardia in children and a much higher prevalence of PGES of longer duration in adults. This may indicate why, despite lower rates of cardiopulmonary dysfunction, adults die more frequently from SUDEP than children.