Electrical Status Epilepticus During Slow Sleep Research Articles

Electrical status epilepticus during slow sleep (ESES) and clinical features of cognitive and behavioral disorders in children with idiopathic forms of epileptic syndromes

Electrical status epilepticus during slow sleep (ESES) and clinical features of cognitive and behavioral disorders in children with idiopathic forms of epileptic syndromes

SQNN: A Spike-wave index Quantification Neural Network with a pre-labeling algorithm for epileptiform activity identification and quantification in children.

Electrical status epilepticus during slow sleep (ESES) is a phenomenon identified by strong activation of epileptiform activity in the electroencephalogram (EEG) during sleep. For children disturbed by ESES, spike-wave index (SWI) is defined to quantify the epileptiform activity in the EEG during sleep. Accurate SWI quantification is important for clinical diagnosis and prognosis. To quantify SWI automatically, a deep learning method is proposed in this paper. Firstly, a pre-labeling algorithm (PreLA) composed of the adaptive wavelet enhanced decomposition and a slow-wave discrimination rule is designed to efficiently label the EEG signal. It enables the collection of large-scale EEG dataset with fine-grained labels. Then, an SWI Quantification Neural Network (SQNN) is constructed to accurately classify each sample point as normal or abnormal and to identify the abnormal events. SWI can be calculated automatically based on the total duration of abnormalities and the length of the signal. Experiments on two datasets demonstrate that the PreLA is effective and robust for labeling the EEG data and the SQNN accurately and reliably quantifies SWI without using any thresholds. The average estimation error of SWI is 3.12%, indicating that our method is more accurate and robust than experts and previous related works. The processing speed of SQNN is 100 times faster than that of experts. Deep learning provides a novel approach to automatic SWI quantification and PreLA provides an easy way to label the EEG data with ESES syndromes. The results of the experiments indicate that the proposed method has a high potential for clinical diagnosis and prognosis of epilepsy in children.

SQNN: a spike-wave index quantification neural network with a pre-labeling algorithm for epileptiform activity identification and quantification in children

Objective. Electrical status epilepticus during slow sleep (ESES) is a phenomenon identified by strong activation of epileptiform activity in the electroencephalogram (EEG) during sleep. For children disturbed by ESES, spike-wave index (SWI) is defined to quantify the epileptiform activity in the EEG during sleep. Accurate SWI quantification is important for clinical diagnosis and prognosis. To quantify SWI automatically, a deep learning method is proposed in this paper. Approach. Firstly, a pre-labeling algorithm (PreLA) composed of the adaptive wavelet enhanced decomposition and a slow-wave discrimination rule is designed to efficiently label the EEG signal. It enables the collection of large-scale EEG dataset with fine-grained labels. Then, an SWI quantification neural network (SQNN) is constructed to accurately classify each sample point as normal or abnormal and to identify the abnormal events. SWI can be calculated automatically based on the total duration of abnormalities and the length of the signal. Main results. Experiments on two datasets demonstrate that the PreLA is effective and robust for labeling the EEG data and the SQNN accurately and reliably quantifies SWI without using any thresholds. The average estimation error of SWI is 3.12%, indicating that our method is more accurate and robust than experts and previous related works. The processing speed of SQNN is 100 times faster than that of experts. Significance. Deep learning provides a novel approach to automatic SWI quantification and PreLA provides an easy way to label the EEG data with ESES syndromes. The results of the experiments indicate that the proposed method has a high potential for clinical diagnosis and prognosis of epilepsy in children.

The Electroencephalographic Evolution of Electrical Status

Purpose: Electrical status epilepticus during slow sleep (ESES) is an electroclinical syndrome with a specific electroencephalogram (EEG) pattern characterized by epileptic seizures, cognitive decline, and behavioral problems. The EEG pattern is defined by the percentage of the spike-wave index (SWI) in nonrapid eye movement (NREM) sleep without a clear cut-off value. The purpose of this study is to determine the significance of SWI calculation in the first 180 s of the NREM sleep stage. Methods: Patients with tonic seizures and those with SWI levels of <50% were excluded from the study. One hundred patients were enrolled in the study (typical ESES: 85; atypical ESES: 15). EEG findings were evaluated according to the following points: 1-ESES type: atypical ESES for SWI between 50% and 85% or typical ESES for ≥85%; 2-SWI calculation methods: Short method and long conventional method; 3-SWI percentage and spike frequency (SF). Results: A moderate correlation was determined between spike-wave percentage (SWP) and SF (r = 0.628; P < 0.001). A strong positive correlation was determined between the short method and long conventional method (r = 0.888; P < 0.001). In multivariate logistic regression with the SWI short method and the number of spikes in the first 180 s of NREM, only the SWI short method was found to predict typical ESES regardless of other factors (odds ratio: 1.18; P = 0.001). The optimal predictive value of the SWI short method for predicting typical ESES was >85, with sensitivity of 81.2%, and specificity of 73.3% (+PV: 94.5%, −PV: 40.7%; AUC ± SE = 0.850 ± 0.05; P < 0.001). Conclusion: Evaluating EEG epileptiform activities with objective and reproducible well-defined measurements such as SWP and SF allows for the comparison of different patient groups. We think that a shorter method for diagnosing ESES would potentially provide increased cost savings and patient comfort.

Epileptic encephalopathy with electrical status epilepticus during slow sleep: evaluation of treatment response from a tertiary center.

This study aimed to evaluate the clinical, electrophysiological, etiological features, and treatment response in children with epileptic encephalopathy with electrical status epilepticus during slow sleep (ESES). Clinical data, records of electroencephalograms (EEG), and brain magnetic resonance imaging (MRI) findings of 33 patients with ESES who were treated, and followed up for at least one year were retrospectively analyzed. Of all patients, 57.6% were male, and 42.4% were female. The mean age was 10.45 ± 2.88 years. At first admission, 90% of patients had seizures, and 10% had only school failure. Twelve patients had childhood focal epileptic syndrome. In etiology, asphyxia (n=6), hydrocephalus (n=2), polymicrogyria (n=1), and mesial temporal sclerosis (n=1) were determined. Neurological examination was abnormal in 27.2%, and brain MRI findings were pathological in 36.3% of the patients. During the ESES phase, the spike-wave index (SWI) on the non-rapid eye movement (NREM) sleep EEG was > 85% in 16 patients and 50-85% in 17 patients. Only one patient received one, and the others had at least two antiseizure medications. Benzodiazepines were found to be the most effective treatment. In the two-year follow-up, 24 patients (72.7%) were seizure-free, and nineteen patients (57.5%) had complete recovery of SWI on their NREM sleep EEG. There was a significant correlation with reduction of the SWI on the EEG and seizure control (p < 0.001). In addition, a significant correlation was found between neurocognitive and behavioral scores scored before and after treatment, seizure control, and EEG recovery. ESES is an epileptic encephalopathy that can be treated safely with antiseizure medications. Neurocognitive examinations and follow-up of EEG findings are valuable in terms of the treatment response. Benzodiazepines were found to be very effective in additional treatment.

Parasagittal hemispherotomy in hemispheric polymicrogyria with electrical status epilepticus during slow sleep: Indications, results and follow-up

PurposePolymicrogyria (PMG), although the most common brain malformation, represents a low percentage among patients operated on for epilepsy. In cases of hemispheric PMG, electrical status epilepticus during slow sleep (ESESS) may occur leading to an aggravation of the neurological condition and a risk of drug resistance. In such cases, surgical treatment can be offered. MethodsFrom a population of 230 children who underwent hemispherotomy for epilepsy, we retrospectively reviewed the patients with unilateral PMG and drug-resistant ESESS focusing on clinical charts, electrophysiological data and post-surgical outcome. ResultsEighteen patients were operated on at a mean age of 7.2 years. The average age was 2 years at seizure onset and 4.4 years at diagnosis of ESESS. All the patients preoperatively had some degree of developmental delay associated with a hemiparesis. During ESESS all of them evidenced a cognitive decline and eight experienced a worsening of the hemiparesis; ESESS was resistant to at least three antiepileptic drugs.The outcome of epilepsy, with a mean follow-up of 12.8 years showed that ESESS disappeared in all patients while 16 of 18 became seizure-free. An improvement of behavior and cognitive condition was observed in all. ConclusionHemispherotomy can be helpful in patients with drug-resistant ESESS and hemispheric PMG while keeping in mind that more often an accurate medical treatment can be sufficient. The main benefit of surgery is to definitively stop the seizures and to withdraw the medical treatment while keeping in mind the risk of motor aggravation.

Seizures and electroencephalography findings in 61 patients with fetal alcohol spectrum disorders

Fetal alcohol spectrum disorders (FASD) cause neurodevelopmental abnormalities. However, publications about epilepsy and electroencephalographic features are scarce. In this study, we prospectively performed electroencephalography (EEG) and brain magnetic resonance (MR) imaging in 61 patients with diagnosis of FASD. One patient had multiple febrile seizures with normal EEGs. Fourteen children showed EEG anomalies, including slow background activity and interictal epileptiform discharges, focal and/or generalized, and 3 of them had epilepsy. In one patient, seizures were first detected during the EEG recording and one case had an encephalopathy with electrical status epilepticus during slow sleep (ESES). Focal interictal discharges in our patients did not imply the presence of underlying visible focal brain lesions in the neuroimaging studies, such as cortical dysplasia or polymicrogyria. However, they had nonspecific brain MR abnormalities, including corpus callosum hypoplasia, vermis hypoplasia or cavum septum pellucidum. The latter was significantly more frequent in the group with EEG abnormal findings (p < 0.01).

Ketogenic diet in patients with epileptic encephalopathy with electrical status epilepticus during slow sleep

Epileptic encephalopathy with electrical status epilepticus during slow sleep (ESES) belongs to the group of epileptic encephalopathies that often prove refractory to AED treatment. The ketogenic diet (KD) has been used as an alternative to antiepileptic drugs (AEDs) for patients with refractory epileptic encephalopathies. In this retrospective study we assess the efficacy and tolerability of the KD in patients with ESES syndrome. Between March 1, 1990 and April 1, 2013, 65 patients who met diagnostic criteria of ESES syndrome were seen at our department. Twelve of them were placed on the KD and followed for a minimum of 18 months. The children had previously received a mean of 5.5 different AEDs and were on a mean of 3 AEDs when the diet was started. Eighteen months after initiating the diet, seven of the initial patients (58%) remained on the diet; one patient (8.3%) had become seizure free, one (8.3%) had a 75-99% decrease in seizures, two (16.6%) had a 50-74% decrease in seizures, and the remaining three children (24.9%) had a <50% decrease in seizures. In the patient who had become seizure free and in the one who had a 75-99% seizure decrease AEDs were reduced. The KD is a well-tolerated treatment option for patients with ESES syndrome, not only for structural cases but also for those with an unknown etiology. The diet should be considered in the management of this syndrome.

Sulthiame add‐on therapy in children with focal epilepsies associated with encephalopathy related to electrical status epilepticus during slow sleep (ESES)

In children with symptomatic or idiopathic focal epilepsies, their disease may evolve into an epileptic encephalopathy related to continuous spike and wave during slow sleep (CSWS) or electrical status epilepticus during slow sleep (ESES). ESES syndrome implies serious risks of neuropsychologic impairment, and its treatment has frequently been disappointing. The aim of this study is to present our experience using sulthiame as add-on treatment in 53 patients with ESES syndrome that was refractory to other antiepileptic drugs (AEDs). Neurologic examinations, cerebral magnetic resonance imaging (MRI), and repeated prolonged sleep electroencephalography (EEG) studies were performed in all cases. Data about school achievements and or neuropsychological evaluations were obtained repeatedly during the follow-up of 1.5-16 years. Sulthiame was added in doses ranging between 5 and 30 mg/kg/day. Since add-on of sulthiame, 10 of 28 patients in the symptomatic group became seizure free: 4 patients with normal EEG studies and 6 with residual spikes. Nine of 28 patients showed a significant reduction in number of seizures and presented spikes but no ESES on EEG. The other nine cases showed neither clinical nor EEG improvement. A striking result was that 3 of 11 children with unilateral polymicrogyria and ESES syndrome became seizure free, and in another six a significant improvement in frequency of seizures and in EEG abnormalities seemed to be related to the add-on of sulthiame. Twenty-one of the 25 patients in the idiopathic group became seizure free and without ESES in <3 months after add on of sulthiame. In two of the patients the changes were seen in a few days. We understand that sulthiame may be effective as add-on treatment in children with ESES syndrome.

Landau‐Kleffner syndrome: 50 years after

Landau‐Kleffner syndrome: 50 years after

Guidelines for EEG in encephalopathy related to ESES/CSWS in children

Electrical status epilepticus during slow sleep (ESES) or continuous spikes and waves during slow sleep (CSWS) is a phenomenon characterized by strong activation of epileptiform activity in the electroencephalogram (EEG) during sleep. The literature contains several small series of patients and many case reports. Large prospective studies are lacking. Definitions of the syndromes and EEG criteria and methods vary, as does their classification. The fluctuating clinical course and EEG findings complicate the diagnostic process and evaluation of effect of therapy. Studies describing quantitative aspects of the epileptiform abnormalities in EEG are overrepresented in literature, whereas qualitative aspects are relatively undervalued. Guidelines for evaluation of the EEG in these syndromes, which focus on both aspects, are presented.

Age-related electrical status epilepticus during sleep and epileptic negative myoclonus in DRPLA

Hereditary dentatorubral-pallidoluysian atrophy (DRPLA) (MIM 125370)1 is a rare autosomal dominant neurodegenerative disorder found mostly in Japanese people and caused by an expansion of the CAG repeat in the DRPLA gene on chromosome 12p.2 Childhood-onset patients generally have a phenotype of progressive myoclonus epilepsy (PME) with a large expansion of the CAG repeat.2 In the present study, we report a patient with DRPLA who showed epilepsy with electrical status epilepticus during slow sleep (ESES) or the extraordinary EEG abnormality of continuous spike-waves during slow wave sleep (CSWS) and epileptic negative myoclonus in childhood. Epilepsy with CSWS generally occurs in cryptogenic patients or symptomatic ones with nonprogressive brain pathology and is an age-related and self-limited disorder.3 Remarkably, his CSWS on EEG remitted spontaneously with age, as it does in other patients without progressive disorder, although the underlying degeneration of the brain continued relentlessly. This patient, who was born after an uneventful pregnancy, had a father with ataxia and dementia and a diagnosis of DRPLA in later life. The patient's early …

Treatment of epilepsy with electrical status epilepticus during slow sleep and its related disorders

To elucidate an effective therapeutic strategy for ‘ESES syndrome’, epilepsy with electrical status epilepticus during slow sleep (ESES) and its related epileptic disorders, we studied the effect of treatment on the EEG pattern of continuous spike-waves during slow wave sleep (CSWS) in 15 afflicted patients. Basically performed in the following order, the employed therapies included (1) high-dose valproate (VPA) therapy (serum level >100 μg/ml); (2) a combination therapy of VPA and ethosuximide (ESM); (3) short cycles of high-dose diazepam (oral or intrarectal DZP, 0.5–1 mg/kg per day for 6–7 days); and (4) intramuscular synthetic ACTH-Z therapy (0.01–0.04 mg/kg per day for 11–43 days). Regarding the initial EEG effect, a remission of CSWS was achieved by high-dose VPA therapy in 7 of 15 trials (47%), by the combination therapy of VPA and ESM in 3/7 trials (43%), by short cycles of high-dose DZP in 2/4 trials (50%), and by ACTH-Z therapy in 2/5 trials (40%). A permanent remission of ESES syndrome was achieved by high-dose VPA therapy and/or combination therapy of VPA and ESM in 10 patients (67%). The effects of short cycles of high-dose DZP and ACTH-Z therapy were at best temporary. Our strategy for the treatment of ESES syndrome is therefore considered valid.

A Clinical and EEG Study on Idiopathic Partial Epilepsies with Evolution into ESES Spectrum Disorders

Questioning the presence of any possible prognostic predictors, this study includes a long-term follow-up of clinical and EEG characteristics of 16 patients with idiopathic partial epilepsy (IPE) who subsequently developed epilepsy with electrical status epilepticus during slow sleep (ESES) spectrum disorders. Epilepsy, cognitive and behavioral parameters, and waking and non-rapid eye movement (NREM) EEG data were evaluated and scored for initial stage (i.e., IPE stage), preESES, ESES, and ESES remission periods, individually, on a chronologic basis. Data from 25 healthy subjects who had had IPE at the appropriate ages served for comparison with the patients' data during the IPE stage. Results revealed a higher incidence in seizure frequency and variability in the ESES group and a resistance to a single antiepileptic drug (AED), as compared with controls, during the IPE stage. Mean age at onset of epilepsy was younger in the ESES group versus controls (5.5 and 7.3 years, respectively). At least one of the premonitory clinical features for development of ESES [an increase in the seizure frequency and/or addition of new types of seizures (93%), appearance of cognitive and/or behavioural changes (81.2%), or a progression in EEG abnormalities (66%)] was present in all patients. Epilepsy remitted in patients within the ESES spectrum at a similar age as in controls in 81.2%, as ESES findings in the EEG disappeared by age 13 years in 94%. Seizure prognosis proved to be the most favorable among the questioned parameters. An increase in seizure frequency or development of new seizure types, a deviance in behavior or decrease in cognitive performance, or a spreading tendency of the previously focal abnormalities in control EEGs may be premonitory features of a developing ESES and necessitate close follow-ups with sleep EEGs in children with IPEs.

Selected Papers: Childhood Epilepsies

Abstract *Miki Inutsuka, †Yoko Ohtsuka, †Kousuke Nakano, †Junri Hattori, *Katsuhiro Kobayashi, and †Eiji Oka Department of Child Neurology, *Okayama University Medical School ; and †Okayama University Graduate School of Medicine and Dentistry, Okayama, Japan . Purpose: To elucidate the effect of treatment of epilepsy with electrical status epilepticus during slow sleep (ESES) and factors related to the response to treatment. Methods: We studied 26 patients with ESES who were admitted to Okayama University Hospital (age range, 2y0m to 9y7m). Patients were treated with one or more of the following therapies: (a) high-dose valproate (VPA) therapy (plasma level, >100 μg/ml), (b) a combination therapy of VPA and ethosuximide (ESM), (c) a short cycle of high-dose diazepam (DZP; 0.54–1 mg/kg/day, orally or intrarectally for 6–14 days), and (d) synthetic adrenocorticotropic hormone (ACTH) therapy (Cortrosyn-Z; 0.01–0.036 mg/kg/day, intramuscularly, for 11–43 days). Basically, we started treatment with high-dose VPA therapy. When this failed or yielded adverse side effects, we tried the combination therapy of VPA and ESM. When both were unsuccessful, we tried a short cycle of high-dose DZP or synthetic ACTH therapy. All patients were followed up for ≥2 years. We also investigated response patterns to treatments and mental outcome in each patient. Results: Treatment effects: Regarding the initial effects, treatment was defined as effective when continuous spike–waves during slow-wave sleep (CSWSs) were suppressed (≥1 month with markedly decreased or no diffuse spike-waves during slow-wave sleep). In terms of initial effect, high-dose VPA was effective in 12 (50%) of 24 trials; combination therapy with VPA and ESM in six (43%) of 14 trials; a short cycle of high-dose DZP, in six (75%) of eight trials; and synthetic ACTH, in three (43%) of seven trials. However, CSWSs recurred within 1 year of treatment in two patients treated with high-dose VPA, in four treated with a short cycle of high-dose DZP, and in all three treated with synthetic ACTH. Response patterns and mental outcomes: Subjects were divided into two groups: 15 patients with favorable EEG response to the initial treatment maintained throughout the clinical course (group A), and 11 patients with no favorable EEG response to the initial treatment, or deterioration after an initial favorable response (group B). All patients except one in group A were treated with high-dose VPA or the combination therapy of VPA and ESM or both. All patients except two in group B were treated with a short cycle of high-dose DZP or synthetic ACTH after the failure of high-dose VPA or both or the combination therapy of VPA and ESM or both. Comparing these two groups, ages at onset of ESES were significantly lower in group B (p = 0.0009). Organic brain lesions such as brain malformations were seen more often in group B. Mental deterioration after the onset of ESES was observed significantly more often in group B (p = 0.037). Regarding mental outcome, patients with normal mentality or slight mental retardation predominated in group A, whereas those with severe mental retardation were found only in group B. Conclusions: Remission of ESES was achieved in approximately half of the patients treated with high-dose VPA therapy or combination therapy with VPA and ESM or both. Even when these treatments were ineffective, a short cycle of high-dose DZP or synthetic ACTH therapy was effective in most cases. However, the effects of the latter two treatments were only temporary. Group B was characterized by early-onset patients associated with organic brain lesions. These patients responded poorly to treatment and consequently had mental deterioration and poor mental outcomes. Thus response to ESES treatment may be related to the underlying organic brain lesion(s). To prevent poor mental outcome, we believe that it is critical to achieve remission as early as possible by using intensive treatment.

Childhood-onset epilepsy associated with polymicrogyria

To study the electroclinical characteristics of patients with childhood-onset epilepsy who showed polymicrogyria (PMG) on MRI, we classified 15 patients according to the location of PMG on MRI. The composition of the subjects was as follows: four patients with PMG in both hemispheres; three with localized PMG in one hemisphere associated with other lesions such as porencephaly; and eight with only localized PMG in one hemisphere. We investigated the electroclinical characteristics of the epileptic syndromes associated with these different types of PMG. Four patients suffered from infantile spasms during their clinical course. Five patients suffered from epilepsy with electrical status epilepticus during slow sleep (ESES) and ESES-related epilepsy. The other six patients had only localization-related epilepsy throughout their clinical course. Patients with PMG in both hemispheres, and localized PMG in one hemisphere associated with other lesions tended to have early-onset intractable seizures, especially infantile spasms. On the other hand, patients with only localized PMG in one hemisphere had ESES and ESES-related epilepsy or localization-related epilepsy, and their seizure prognosis was relatively favorable. These findings are useful in predicting the outcome of patients with PMG.

Nonconvulsive status epilepticus with continuous diffuse spike-and-wave discharges during sleep in childhood.

On three epileptic conditions with common characteristics of almost continuous diffuse spike-and-wave discharges during sleep in EEG, clinical and electroencephalographic studies were undertaken to elucidate their pathophysiologies and interrelationships; namely on five cases of epilepsy with electrical status epilepticus during slow sleep (ESES), seven cases of a peculiar type of nonconvulsive status epilepticus in childhood (PNSE) and three cases of atypical benign partial epilepsy (ABPE). The dominant seizure types were absences and/or GTC in ESES, whereas they were focal motor seizures in PNSE and ABPE with more focalized epileptic discharges on EEGs than those in ESES. All the three conditions showed both features of generalized and partial epilepsies, although the former features were more prominent in ESES and the latter in PNSE and ABPE.